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Conserved domains on  [gi|1958775623|ref|XP_038965557|]
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ephrin type-A receptor 10 isoform X1 [Rattus norvegicus]

Protein Classification

ephrin type-A receptor; ephrin type-A receptor 7( domain architecture ID 10917954)

ephrin type-A receptor is a receptor protein-tyrosine kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates, and binds GPI-anchored ephrin-A ligands| ephrin type-A receptor 7 is a receptor tyrosine kinase that catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates; it binds promiscuously to GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 638-956 8.37e-170

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05064:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 266  Bit Score: 498.29  E-value: 8.37e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05064      1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd05064     81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFS 877
Cdd:cd05064    161 AIYTTM------------------------------------------------------SGKSPVLWAAPEAIQYHHFS 186

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05064    187 SASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQIHSILSKM 265
EphR_LBD super family cl02704
Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest ...
 35-210 7.18e-121

Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). They are subdivided into 2 groups, A and B type receptors, depending on their ligand ephrin-A or ephrin-B, respectively. In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


The actual alignment was detected with superfamily member cd10487:

Pssm-ID: 470656  Cd Length: 173  Bit Score: 367.43  E-value: 7.18e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10487      1 EVVLLDSKESQAELGWTSLPSNGWEEISGVDEHYKPIRTYQVCNVMEPNQNNWLQTGWISRGRGQRIFIELQFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10487     81 IPGVAGTCKETFNLYYAESDADLGR---RLRESRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGHLSRRGFHLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10487    158 VGACVALVSVRVYYKQ 173
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 982-1051 8.50e-38

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


:

Pssm-ID: 188948  Cd Length: 70  Bit Score: 135.76  E-value: 8.50e-38
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  982 FSAFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09549      1 FSTFPSFGSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
 569-641 6.75e-20

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


:

Pssm-ID: 464211  Cd Length: 72  Bit Score: 84.58  E-value: 6.75e-20
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  569 TVVTISALLVLGSVMSVLAIWRRPCDGKGSGnAHDEEELYFHFKVPTRRTFLDPQSCGDPLQAVHLFAKELDA 641
Cdd:pfam14575    1 VVASVAGGLVLLLVVGVVLIRRRRCCGRKKS-QDDDEEEFHQYKPPGRKTYIDPHTYEDPNQAVLEFAKEIDA 72
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 451-551 5.48e-11

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


:

Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 59.82  E-value: 5.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  451 PGAPweeDEIRRDRVEPQSVSLSWREPVPAGASGTNrteYEIRYYEKGQSE-QTYSTVKTGAPAVTVTNLKPATRYVFQI 529
Cdd:cd00063      1 PSPP---TNLRVTDVTSTSVTLSWTPPEDDGGPITG---YVVEYREKGSGDwKEVEVTPGSETSYTLTGLKPGTEYEFRV 74

                           90       100
                   ....*....|....*....|...
gi 1958775623  530 RAASP-GPSweaqSFSPSIEVQT 551
Cdd:cd00063     75 RAVNGgGES----PPSESVTVTT 93
fn3 pfam00041
Fibronectin type III domain;
339-431 1.51e-06

Fibronectin type III domain;


:

Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 47.02  E-value: 1.51e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  339 SAPRDLQYSlSRSPLALRLRWLPPEDSGGrSDVTYSLLCLRCGRDGPagacqpcgPRVAFVPRQaglrERAATLLHLRPG 418
Cdd:pfam00041    1 SAPSNLTVT-DVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEP--------WNEITVPGT----TTSVTLTGLKPG 66

                           90
                   ....*....|...
gi 1958775623  419 ARYTVRVAALNGV 431
Cdd:pfam00041   67 TEYEVRVQAVNGG 79
 
Name Accession Description Interval E-value
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
 638-956 8.37e-170

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 498.29  E-value: 8.37e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05064      1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd05064     81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFS 877
Cdd:cd05064    161 AIYTTM------------------------------------------------------SGKSPVLWAAPEAIQYHHFS 186

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05064    187 SASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQIHSILSKM 265
EphR_LBD_A10 cd10487
Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the ...
 35-210 7.18e-121

Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction results in cell-cell repulsion or adhesion.


Pssm-ID: 198455  Cd Length: 173  Bit Score: 367.43  E-value: 7.18e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10487      1 EVVLLDSKESQAELGWTSLPSNGWEEISGVDEHYKPIRTYQVCNVMEPNQNNWLQTGWISRGRGQRIFIELQFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10487     81 IPGVAGTCKETFNLYYAESDADLGR---RLRESRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGHLSRRGFHLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10487    158 VGACVALVSVRVYYKQ 173
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 644-953 3.00e-101

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 319.06  E-value: 3.00e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCL-QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLkGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFgrgprdraeavytt 802
Cdd:pfam07714   81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDF-------------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllllsaiptgpmvyilalppslpGLFPLVvpclsQPGSFLRCGGSGRSPALWAAPETLQFGHFSSASDV 882
Cdd:pfam07714  147 ----------------------------------GLSRDI-----YDDDYYRKRGGGKLPIKWMAPESLKDGKFTSKSDV 187

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  883 WSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:pfam07714  188 WSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 644-953 1.03e-91

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 293.28  E-value: 1.03e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   644 VTLEKSLGAGRFGDLCCGCL-QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLkGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTT 802
Cdd:smart00219   81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLS-RDLYDDDYYR 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   803 MvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGHFSSASDV 882
Cdd:smart00219  160 K-----------------------------------------------------RGGKLPIRWMAPESLKEGKFTSKSDV 186

                           250       260       270       280       290       300       310
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623   883 WSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:smart00219  187 WSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
35-209 1.99e-91

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 289.57  E-value: 1.99e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623    35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:smart00615    1 EVVLLDTKTETGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSS 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   115 IPGATGTCKETFNAYYLETEADLGRG-HPHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:smart00615   81 LPGVGGSCKETFNLYYYESDTDTATNtLPNWMENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQ 160

                           170
                    ....*....|....*.
gi 1958775623   194 DVGACVALVSVRVYYK 209
Cdd:smart00615  161 DQGACVALVSVRVFYK 176
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
 36-211 3.25e-86

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 275.31  E-value: 3.25e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   36 VTLLDSKASQAELGWTALP-STGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:pfam01404    1 EVLLDTTSATSDLGWTTYPyDGGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLG-RGHPHLGGNRPRKIDTIAADESFTQGDlGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:pfam01404   81 IPGVSGTCKETFNLYYYESDADAAtATPPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQ 159

                          170
                   ....*....|....*...
gi 1958775623  194 DVGACVALVSVRVYYKQC 211
Cdd:pfam01404  160 DQGACIALLSVRVFYKKC 177
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 982-1051 8.50e-38

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188948  Cd Length: 70  Bit Score: 135.76  E-value: 8.50e-38
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  982 FSAFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09549      1 FSTFPSFGSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
 569-641 6.75e-20

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 84.58  E-value: 6.75e-20
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  569 TVVTISALLVLGSVMSVLAIWRRPCDGKGSGnAHDEEELYFHFKVPTRRTFLDPQSCGDPLQAVHLFAKELDA 641
Cdd:pfam14575    1 VVASVAGGLVLLLVVGVVLIRRRRCCGRKKS-QDDDEEEFHQYKPPGRKTYIDPHTYEDPNQAVLEFAKEIDA 72
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
645-944 3.93e-17

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 85.83  E-value: 3.93e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRqelPVAVHTLREGCSDSQKL--SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:COG0515     10 RILRLLGRGGMGVVYLARDLRLGR---PVALKVLRPELAADPEAreRFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAeLVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavytt 802
Cdd:COG0515     87 EYVEGESLADLLRRRGP-LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFG------------- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllllsaiptgpmvyiLALPPSLPGlfplvvpcLSQPGSFLrcgGSgrspALWAAPETLQFGHFSSASDV 882
Cdd:COG0515    153 --------------------------IARALGGAT--------LTQTGTVV---GT----PGYMAPEQARGEPVDPRSDV 191

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  883 WSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGFRLPPPR---NCPSQLHRLMLECWQKDPGERP 944
Cdd:COG0515    192 YSLGVTLYE-LLTGRPPFDGDSPAELLRAHLREPPPPPSElrpDLPPALDAIVLRALAKDPEERY 255
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
985-1048 5.83e-15

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 70.38  E-value: 5.83e-15
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQ 1048
Cdd:pfam07647    3 SWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
 984-1050 1.43e-13

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 66.55  E-value: 1.43e-13
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623   984 AFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTR 1050
Cdd:smart00454    2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 451-551 5.48e-11

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 59.82  E-value: 5.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  451 PGAPweeDEIRRDRVEPQSVSLSWREPVPAGASGTNrteYEIRYYEKGQSE-QTYSTVKTGAPAVTVTNLKPATRYVFQI 529
Cdd:cd00063      1 PSPP---TNLRVTDVTSTSVTLSWTPPEDDGGPITG---YVVEYREKGSGDwKEVEVTPGSETSYTLTGLKPGTEYEFRV 74

                           90       100
                   ....*....|....*....|...
gi 1958775623  530 RAASP-GPSweaqSFSPSIEVQT 551
Cdd:cd00063     75 RAVNGgGES----PPSESVTVTT 93
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 451-531 6.98e-11

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 59.55  E-value: 6.98e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   451 PGAPWEedeIRRDRVEPQSVSLSWREPVPAGASGtNRTEYEIRYYEKGQSEQTYsTVKTGAPAVTVTNLKPATRYVFQIR 530
Cdd:smart00060    1 PSPPSN---LRVTDVTSTSVTLSWEPPPDDGITG-YIVGYRVEYREEGSEWKEV-NVTPSSTSYTLTGLKPGTEYEFRVR 75


                    .
gi 1958775623   531 A 531
Cdd:smart00060   76 A 76
fn3 pfam00041
Fibronectin type III domain;
469-533 1.00e-08

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 53.19  E-value: 1.00e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  469 SVSLSWREPVPAGASGTNrteYEIRYYEKG-QSEQTYSTVKTGAPAVTVTNLKPATRYVFQIRAAS 533
Cdd:pfam00041   15 SLTVSWTPPPDGNGPITG---YEVEYRPKNsGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVN 77
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
415-589 5.18e-08

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 56.93  E-value: 5.18e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  415 LRPGARYTVRVAALNG---VSGPAAAagatyaqVTVSTGPGAPWEEDEIRRDRVEPQSVSLSWrepvpAGASGTNRTEYE 491
Cdd:COG3401    292 LTNGTTYYYRVTAVDAagnESAPSNV-------VSVTTDLTPPAAPSGLTATAVGSSSITLSW-----TASSDADVTGYN 359

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  492 IryYEKGQSEQTYSTVKTGAPAV--TVTNLKPATRYVFQIRAASPGPSWEAQSFSPSIEVQTPGEVAPGSRDQSPAVVVT 569
Cdd:COG3401    360 V--YRSTSGGGTYTKIAETVTTTsyTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVDAVPLTD 437

                          170       180
                   ....*....|....*....|
gi 1958775623  570 VVTISALLVLGSVMSVLAIW 589
Cdd:COG3401    438 VAGATAAASAASNPGVSAAV 457
fn3 pfam00041
Fibronectin type III domain;
339-431 1.51e-06

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 47.02  E-value: 1.51e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  339 SAPRDLQYSlSRSPLALRLRWLPPEDSGGrSDVTYSLLCLRCGRDGPagacqpcgPRVAFVPRQaglrERAATLLHLRPG 418
Cdd:pfam00041    1 SAPSNLTVT-DVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEP--------WNEITVPGT----TTSVTLTGLKPG 66

                           90
                   ....*....|...
gi 1958775623  419 ARYTVRVAALNGV 431
Cdd:pfam00041   67 TEYEVRVQAVNGG 79
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 338-434 3.96e-06

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 46.34  E-value: 3.96e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  338 PSAPRDLQYSlSRSPLALRLRWLPPEDSGGRSDvTYSLLClrcgRDGPAGACQPCGPRVAfvprqaglRERAATLLHLRP 417
Cdd:cd00063      1 PSPPTNLRVT-DVTSTSVTLSWTPPEDDGGPIT-GYVVEY----REKGSGDWKEVEVTPG--------SETSYTLTGLKP 66

                           90
                   ....*....|....*....
gi 1958775623  418 GARYTVRVAALN--GVSGP 434
Cdd:cd00063     67 GTEYEFRVRAVNggGESPP 85
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 338-431 5.04e-06

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 45.68  E-value: 5.04e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   338 PSAPRDLQYSlSRSPLALRLRWLPPEDSGGRSDVTYsllCLRCGRDGpagacqpcGPRVAFVPRQAglRERAATLLHLRP 417
Cdd:smart00060    1 PSPPSNLRVT-DVTSTSVTLSWEPPPDDGITGYIVG---YRVEYREE--------GSEWKEVNVTP--SSTSYTLTGLKP 66

                            90
                    ....*....|....
gi 1958775623   418 GARYTVRVAALNGV 431
Cdd:smart00060   67 GTEYEFRVRAVNGA 80
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 865-949 1.34e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 48.86  E-value: 1.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAFgERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:PTZ00267   237 YLAPELWERKRYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRP 315


                   ....*
gi 1958775623  945 RFSQI 949
Cdd:PTZ00267   316 TTQQL 320
 
Name Accession Description Interval E-value
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
 638-956 8.37e-170

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 498.29  E-value: 8.37e-170
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05064      1 ELDNKSIKIERILGTGRFGELCRGCLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRGNT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd05064     81 MMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRRLQEDKSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFS 877
Cdd:cd05064    161 AIYTTM------------------------------------------------------SGKSPVLWAAPEAIQYHHFS 186

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05064    187 SASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQIHSILSKM 265
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
 639-956 5.13e-155

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 460.30  E-value: 5.13e-155
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05033      1 IDASYVTIEKVIGGGEFGEVCSGSLKLPGKKEIDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTKSRPV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDR-AE 797
Cdd:cd05033     81 MIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEdSE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFS 877
Cdd:cd05033    161 ATYTTK------------------------------------------------------GGKIPIRWTAPEAIAYRKFT 186

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05033    187 SASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDRNERPTFSQIVSTLDKM 265
EphR_LBD_A10 cd10487
Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the ...
 35-210 7.18e-121

Ligand Binding Domain of Ephrin type-A Receptor 10; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction results in cell-cell repulsion or adhesion.


Pssm-ID: 198455  Cd Length: 173  Bit Score: 367.43  E-value: 7.18e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10487      1 EVVLLDSKESQAELGWTSLPSNGWEEISGVDEHYKPIRTYQVCNVMEPNQNNWLQTGWISRGRGQRIFIELQFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10487     81 IPGVAGTCKETFNLYYAESDADLGR---RLRESRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGHLSRRGFHLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10487    158 VGACVALVSVRVYYKQ 173
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
 639-956 3.09e-116

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 359.18  E-value: 3.09e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05066      1 IDASCIKIEKVIGAGEFGEVCSGRLKLPGKREIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKPV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG--RGPRDRA 796
Cdd:cd05066     81 MIVTEYMENGSLDAFLRKHDGQFTVIQLVGMLRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGlsRVLEDDP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 EAVYTTmvrssllwphmllllsaipTGpmvyilalppslpglfplvvpclsqpgsflrcggsGRSPALWAAPETLQFGHF 876
Cdd:cd05066    161 EAAYTT-------------------RG-----------------------------------GKIPIRWTAPEAIAYRKF 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05066    187 TSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQKDRNERPKFEQIVSILDKL 266
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
 639-956 6.14e-108

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 337.23  E-value: 6.14e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05065      1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPGKREIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRPV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRG---PRDR 795
Cdd:cd05065     81 MIITEFMENGALDSFLRQNDGQFTVIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSrflEDDT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 AEAVYTTMVrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGH 875
Cdd:cd05065    161 SDPTYTSSL-----------------------------------------------------GGKIPIRWTAPEAIAYRK 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  876 FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05065    188 FTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDCWQKDRNLRPKFGQIVNTLDK 267


                   .
gi 1958775623  956 M 956
Cdd:cd05065    268 M 268
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
 638-956 2.86e-104

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 327.32  E-value: 2.86e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05063      1 EIHPSHITKQKVIGAGEFGEVFRGILKMPGRKEVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG--RGPRDR 795
Cdd:cd05063     81 AMIITEYMENGALDKYLRDHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGlsRVLEDD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 AEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGH 875
Cdd:cd05063    161 PEGTYTT------------------------------------------------------SGGKIPIRWTAPEAIAYRK 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  876 FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05063    187 FTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVYQLMLQCWQQDRARRPRFVDIVNLLDK 266


                   .
gi 1958775623  956 M 956
Cdd:cd05063    267 L 267
EphR_LBD_A cd10473
Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the ...
 35-210 2.27e-103

Ligand Binding Domain of Ephrin type-A Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198441  Cd Length: 173  Bit Score: 321.31  E-value: 2.27e-103
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10473      1 EVVLLDSKTAQGELGWITYPPNGWEEISEMDEDYTPIRTYQVCNVMEPNQNNWLRTNWIYRGEAQRIYIELKFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10473     81 FPGVLGTCKETFNLYYMESDLDLGR---NIRENQFTKIDTIAADESFTQGDLGDRIMKLNTEVREVGPLTKKGFYLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10473    158 VGACVALVSVRVYYKK 173
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 644-953 3.00e-101

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 319.06  E-value: 3.00e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCL-QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLkGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFgrgprdraeavytt 802
Cdd:pfam07714   81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDF-------------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllllsaiptgpmvyilalppslpGLFPLVvpclsQPGSFLRCGGSGRSPALWAAPETLQFGHFSSASDV 882
Cdd:pfam07714  147 ----------------------------------GLSRDI-----YDDDYYRKRGGGKLPIKWMAPESLKDGKFTSKSDV 187

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  883 WSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:pfam07714  188 WSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFSELVEDL 258
EphR_LBD_A7 cd10485
Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the ...
 33-211 4.27e-94

Ligand Binding Domain of Ephrin type-A Receptor 7; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA7 has been implicated in various cancers, including prostate, gastic and colorectal cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198453  Cd Length: 177  Bit Score: 296.56  E-value: 4.27e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   33 AEEVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDC 112
Cdd:cd10485      1 AKEVILLDSKAQQTELEWISSPPSGWEEISGLDENYTPIRTYQVCQVMEPNQNNWLRTNWISKGNAQRIFVELKFTLRDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  113 SSIPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAF 192
Cdd:cd10485     81 NSLPGVLGTCKETFNLYYYETDYDTGR---NIRENQYVKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSKKGFYLAF 157

                          170
                   ....*....|....*....
gi 1958775623  193 QDVGACVALVSVRVYYKQC 211
Cdd:cd10485    158 QDVGACIALVSVKVYYKKC 176
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 644-953 1.03e-91

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 293.28  E-value: 1.03e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   644 VTLEKSLGAGRFGDLCCGCL-QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLkGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTT 802
Cdd:smart00219   81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLS-RDLYDDDYYR 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   803 MvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGHFSSASDV 882
Cdd:smart00219  160 K-----------------------------------------------------RGGKLPIRWMAPESLKEGKFTSKSDV 186

                           250       260       270       280       290       300       310
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623   883 WSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:smart00219  187 WSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
EPH_lbd smart00615
Ephrin receptor ligand binding domain;
35-209 1.99e-91

Ephrin receptor ligand binding domain;


Pssm-ID: 128877  Cd Length: 177  Bit Score: 289.57  E-value: 1.99e-91
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623    35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:smart00615    1 EVVLLDTKTETGELGWTTYPPEGWEEVSGMDENGTPIRTYQVCNVQEGNQNNWLRTNFIRRRGAQRIYVELKFTVRDCSS 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   115 IPGATGTCKETFNAYYLETEADLGRG-HPHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:smart00615   81 LPGVGGSCKETFNLYYYESDTDTATNtLPNWMENPYTKVDTIAADESFTGGDVGKRNVKLNTEVRSLGPLSKKGFYLAFQ 160

                           170
                    ....*....|....*.
gi 1958775623   194 DVGACVALVSVRVYYK 209
Cdd:smart00615  161 DQGACVALVSVRVFYK 176
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
 644-953 2.70e-90

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 289.45  E-value: 2.70e-90
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   644 VTLEKSLGAGRFGDLCCGCL-QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLkGKGDGKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   723 EYMNLGALDDFLR-HHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYT 801
Cdd:smart00221   81 EYMPGGDLLDYLRkNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLS-RDLYDDDYY 159

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   802 TMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGHFSSASD 881
Cdd:smart00221  160 KV-----------------------------------------------------KGGKLPIRWMAPESLKEGKFTSKSD 186

                           250       260       270       280       290       300       310
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623   882 VWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:smart00221  187 VWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 650-953 7.98e-87

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 280.19  E-value: 7.98e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd00192      3 LGEGAFGEVYKGKLKGGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGD 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLR--------HHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYT 801
Cdd:cd00192     83 LLDFLRksrpvfpsPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLS-RDIYDDDYY 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 TMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFGHFSSASD 881
Cdd:cd00192    162 RK----------------------------------------------------KTGGKLPIRWMAPESLKDGIFTSKSD 189

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  882 VWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd00192    190 VWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELMLSCWQLDPEDRPTFSELVERL 261
EphR_LBD_A3 cd10481
Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the ...
 35-210 3.22e-86

Ligand Binding Domain of Ephrin type-A Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA3 has been implicated in leukemia, lung and other cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198449  Cd Length: 173  Bit Score: 275.40  E-value: 3.22e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10481      1 EVNLLDSKAIQGELGWISYPSHGWEEISGVDEHYTPIRTYQVCNVMDHSQNNWLRTNWIPRNSAQKIYVELKFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADlgrghphlGGNRPR-----KIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFH 189
Cdd:cd10481     81 IPLVLGTCKETFNLYYMESDED--------QGVKFRehqftKIDTIAADESFTQMDLGDRILKLNTEVREVGPVSKKGFY 152

                          170       180
                   ....*....|....*....|.
gi 1958775623  190 LAFQDVGACVALVSVRVYYKQ 210
Cdd:cd10481    153 LAFQDVGACVALVSVRVYFKK 173
Ephrin_lbd pfam01404
Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are ...
 36-211 3.25e-86

Ephrin receptor ligand binding domain; The Eph receptors, which bind to ephrins pfam00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand.


Pssm-ID: 460198  Cd Length: 177  Bit Score: 275.31  E-value: 3.25e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   36 VTLLDSKASQAELGWTALP-STGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:pfam01404    1 EVLLDTTSATSDLGWTTYPyDGGWEEVSGLDENGRTIRTYQVCNVEEPNQNNWLRTPFIPRGGASRVYVELKFTVRDCSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLG-RGHPHLGGNRPRKIDTIAADESFTQGDlGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:pfam01404   81 IPGVSGTCKETFNLYYYESDADAAtATPPAWRENPYKKIDTIAADESFTDTG-KGRVMKLNTETRSIGPLSKRGFYLAFQ 159

                          170
                   ....*....|....*...
gi 1958775623  194 DVGACVALVSVRVYYKQC 211
Cdd:pfam01404  160 DQGACIALLSVRVFYKKC 177
EphR_LBD_A6 cd10484
Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the ...
 35-210 2.10e-81

Ligand Binding Domain of Ephrin type-A Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA6, like other Eph receptors and their ephrin ligands, seems to play a role in neural development, underlying learning and memory. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198452  Cd Length: 173  Bit Score: 262.26  E-value: 2.10e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10484      1 QVVLLDTTMVLGELNWKTYPCNGWDAITEMDEYNRPIHTYQVCNVMEPNQNNWLRTNWISRDAAQKIYVEMKFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLET-EADLGRGHPhlggNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:cd10484     81 IPWVVGTCKETFNLHYMESdEAHAVKFKP----NQYSKIDTIAADESFTQMDLGDRILKLNTEVREVGPITRKGFYLAFQ 156

                          170
                   ....*....|....*..
gi 1958775623  194 DVGACVALVSVRVYYKQ 210
Cdd:cd10484    157 DIGACIALVSVRVYYKK 173
EphR_LBD_B cd10472
Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the ...
 37-210 8.18e-81

Ligand Binding Domain of Ephrin type-B receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. They play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphB receptors are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198440  Cd Length: 176  Bit Score: 260.58  E-value: 8.18e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   37 TLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIP 116
Cdd:cd10472      2 TLMDTRTATAELGWTAHPPSGWEEVSGYDENMNTIRTYQVCNVFESNQNNWLRTKFIRRRGAHRVYVEMKFTVRDCSSIP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  117 GATGTCKETFNAYYLETEADLG-RGHPHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQDV 195
Cdd:cd10472     82 NVPGSCKETFNLYYYESDSDIAtKTSPFWMENPYVKVDTIAADESFSQVDLGGRVMKVNTEVRSFGPLSRNGFYLAFQDY 161

                          170
                   ....*....|....*
gi 1958775623  196 GACVALVSVRVYYKQ 210
Cdd:cd10472    162 GACMSLISVRVFYKK 176
EphR_LBD_A4 cd10482
Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the ...
 35-210 5.64e-80

Ligand Binding Domain of Ephrin type-A Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. A loss of EphA4, as well as EphB2, precedes memory decline in a murine model of Alzheimers disease. EphA4 has been shown to have a negative effect on axon regeneration and functional restoration in corticospinal lesions and is downregulated in some cervical cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198450  Cd Length: 174  Bit Score: 258.43  E-value: 5.64e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTG-WEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCS 113
Cdd:cd10482      1 EVTLLDSRSVQGELGWIASPLEGgWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWIPREGAQRVYIEIKFTLRDCN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  114 SIPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:cd10482     81 SLPGVMGTCKETFNLYYYESNNDKER---FIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEVRDVGPLSKKGFYLAFQ 157

                          170
                   ....*....|....*..
gi 1958775623  194 DVGACVALVSVRVYYKQ 210
Cdd:cd10482    158 DVGACIALVSVRVFYKK 174
EphR_LBD_A5 cd10483
Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the ...
 35-210 6.74e-80

Ligand Binding Domain of Ephrin type-A Receptor 5; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA5 is almost exclusively expressed in the nervous system. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198451  Cd Length: 173  Bit Score: 258.04  E-value: 6.74e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10483      1 EVNLLDSRSVMGDLGWIAYPKNGWEEIGEVDENYAPIHTYQVCKVMEQNQNNWLLTSWISNEGASRIFIELKFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRghpHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10483     81 LPGGLGTCKETFNVYYFESNDEDGR---NIRENQYIKIDTIAADESFTELDLGDRVMKLNTEVRDVGPLTKKGFYLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10483    158 LGACIALVSVRVYYKK 173
EphR_LBD_A8 cd10486
Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the ...
 35-210 7.34e-78

Ligand Binding Domain of Ephrin type-A Receptor 8; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA8 has been implicated in various cancers. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198454  Cd Length: 173  Bit Score: 252.65  E-value: 7.34e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10486      1 EVNLLDTSTISGDWGWLTYPSHGWDSINEMDEYFSPIHTYQVCNVMSPNQNNWLRTNWVQRDGARRVYAEIKFTLRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRGhphLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQD 194
Cdd:cd10486     81 MPGVLGTCKETFNLYYYESDRDLGTS---TWESQFLKIDTIAADESFTNVDLGVRRLKLNTEVRGVGPLSKRGFYLAFQD 157

                          170
                   ....*....|....*.
gi 1958775623  195 VGACVALVSVRVYYKQ 210
Cdd:cd10486    158 IGACIAIVSVRVYYKK 173
EphR_LBD_B1 cd10476
Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the ...
 37-210 8.89e-74

Ligand Binding Domain of Ephrin type-B Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. Using EphB1 knockout-mice, EphB1 has been shown to be essential to the development of long-term potentiation (LTP), a cellular model of synaptic plasticity, learning and memory formation. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198444  Cd Length: 176  Bit Score: 241.50  E-value: 8.89e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   37 TLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSSIP 116
Cdd:cd10476      2 TLMDTRTATAELGWTANPASGWEEVSGYDENLNTIRTYQVCNVFEPNQNNWLLTTFINRRGAHRIYTEMRFTVRDCSSLP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  117 GATGTCKETFNAYYLETEADLGRGHPHLGGNRPR-KIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQDV 195
Cdd:cd10476     82 NVPGSCKETFNLYYYETDSVIATKKSAFWTEAPYlKVDTIAADESFSQVDFGGRLMKVNTEVRSFGPLTRNGFYLAFQDY 161

                          170
                   ....*....|....*
gi 1958775623  196 GACVALVSVRVYYKQ 210
Cdd:cd10476    162 GACMSLLSVRVFFKK 176
EphR_LBD_B3 cd10478
Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the ...
 35-210 2.35e-72

Ligand Binding Domain of Ephrin type-B Receptor 3; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB3 plays a role in cell positioning in the gastrointestinal tract by being preferentially expressed in Paneth cells. It also has been implicated in early colorectal cancer and early stage squamous cell lung cancer. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198446  Cd Length: 173  Bit Score: 237.21  E-value: 2.35e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10478      1 EETLMDTKWVTSELAWTTHPESGWEEVSGYDEAMNPIRTYQVCNVRESNQNNWLRTGFIPRRDVQRVYVELKFTVRDCNS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLGRGH-PHLGGNRPRKIDTIAADESFTQGDLGerkmKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:cd10478     81 IPNIPGSCKETFNLFYYESDSDSASASsPFWMENPYVKVDTIAPDESFSRLDSG----RVNTKVRSFGPLSKAGFYLAFQ 156

                          170
                   ....*....|....*..
gi 1958775623  194 DVGACVALVSVRVYYKQ 210
Cdd:cd10478    157 DLGACMSLISVRAFFKK 173
EphR_LBD cd10319
Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest ...
 36-209 8.16e-72

Ligand Binding Domain of Ephrin Receptors; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). They are subdivided into 2 groups, A and B type receptors, depending on their ligand ephrin-A or ephrin-B, respectively. In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.


Pssm-ID: 198439  Cd Length: 177  Bit Score: 236.15  E-value: 8.16e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   36 VTLLDSKASQAELGWTALP--STGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCS 113
Cdd:cd10319      1 VVLLDTTLATSDLGWLTYPygHGGWDEESGLDPDGANIRTYVVCNVAMPNQDNWLRTPFIERRGAQRIYVELKFTVRDCE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  114 SIPGATGTCKETFNAYYLETEADLG-RGHPHLGGNRPRKIDTIAADESFTQGDlGERKMKLNTEVREIGPLSRQGFHLAF 192
Cdd:cd10319     81 SFPGNARSCKETFNLYYYESDHDTAtKEFPPWNEDPYTKIDTIAADESFKSSN-EDTTEKLNTETRSIGPLTKRGFYLAF 159

                          170
                   ....*....|....*..
gi 1958775623  193 QDVGACVALVSVRVYYK 209
Cdd:cd10319    160 QDQGACMSLLSVKVYYK 176
EphR_LBD_B2 cd10477
Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the ...
 35-210 4.14e-71

Ligand Binding Domain of Ephrin type-B Receptor 2; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells. It also has been implicated in colorectal cancer. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198445  Cd Length: 178  Bit Score: 234.18  E-value: 4.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCSS 114
Cdd:cd10477      2 EETLMDSTTATAELGWMVHPPSGWEEVSGYDENMNTIRTYQVCNVFESSQNNWLRTKYIRRRGAHRIHVEMKFSVRDCSS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  115 IPGATGTCKETFNAYYLETEADLG-RGHPHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:cd10477     82 IPSVPGSCKETFNLYYYESDFDSAtKTFPNWMENPWVKVDTIAADESFSQVDLGGRVMKINTEVRSFGPVSRNGFYLAFQ 161

                          170
                   ....*....|....*..
gi 1958775623  194 DVGACVALVSVRVYYKQ 210
Cdd:cd10477    162 DYGGCMSLIAVRVFYRK 178
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 648-954 2.16e-68

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 229.54  E-value: 2.16e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVvTRGNPLMIVTEYMNL 727
Cdd:cd05060      1 KELGHGNFGSVRKGVYLMKSGKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGV-CKGEPLMLVMELAPL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEaELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttMVRss 807
Cdd:cd05060     80 GPLLKYLKKRR-EIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFG-------------MSR-- 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  808 llwphmllllsAIPTGPMVYilalppslpglfplvvpclsqpgsflRCGGSGRSPALWAAPETLQFGHFSSASDVWSFGI 887
Cdd:cd05060    144 -----------ALGAGSDYY--------------------------RATTAGRWPLKWYAPECINYGKFSSKSDVWSYGV 186

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  888 VMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05060    187 TLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPEDRPTFSELESTFR 253
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
 638-954 4.75e-67

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 226.84  E-value: 4.75e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQ--LPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05032      2 ELPREKITLIRELGQGSFGMVYEGLAKgvVKGEPETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHH--EAELV------TAQLMGLLPG-LASAMKYLSEMGYVHRGLAARRVLLSSGLICKIS 786
Cdd:cd05032     82 QPTLVVMELMAKGDLKSYLRSRrpEAENNpglgppTLQKFIQMAAeIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  787 GFGRGpRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPALWA 866
Cdd:cd05032    162 DFGMT-RD----IYET------------------------------------------------DYYRKGGKGLLPVRWM 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd05032    189 APESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHLDLPENCPDKLLELMRMCWQYNPKMRPTF 268


                   ....*...
gi 1958775623  947 SQIHSILS 954
Cdd:cd05032    269 LEIVSSLK 276
EphR_LBD_A2 cd10480
Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of ...
 35-211 1.25e-66

Ligand Binding Domain of Ephrin type-A Receptor 2; EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA2 negatively regulates cell differentiation and has been shown to be overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198448  Cd Length: 174  Bit Score: 221.64  E-value: 1.25e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALP-STGWEEISGVdEHDRPIRTYQVCNVLEPNQDNWLQTGWISRGRGQRIFVELQFTLRDCS 113
Cdd:cd10480      1 EVVLLDFAAAGGELGWLTHPyGKGWDLMQNV-MNDSPIYMYSVCNVMSGEQDNWLRTNWIYRSEAERIFIELKFTVRDCN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  114 SIPGATGTCKETFNAYYLETEADLGrghPHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHLAFQ 193
Cdd:cd10480     80 SFPGGAGSCKETFNLYYAESDVDYG---TNFQKRQFRKIDTIAPDEITVSSDFETRNVKLNVEERSVGPLTRKGFYLAFQ 156

                          170
                   ....*....|....*...
gi 1958775623  194 DVGACVALVSVRVYYKQC 211
Cdd:cd10480    157 DIGACVALLSVRVYYKKC 174
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
 648-953 8.56e-65

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 219.08  E-value: 8.56e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLqlpgRQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd05034      1 KKLGAGQFGEVWMGVW----NGTTKVAVKTLKPGTMSPE--AFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSK 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTtmvrs 806
Cdd:cd05034     75 GSLLDYLRTGEGRALRlPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLA-RLIEDDEYT----- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 sllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSflrcggsgRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd05034    149 ----------------------------------------AREGA--------KFPIKWTAPEAALYGRFTIKSDVWSFG 180

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  887 IVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05034    181 ILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPTFEYLQSFL 247
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 638-954 5.64e-64

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 217.22  E-value: 5.64e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQlpGRQelpVAVHTLRegCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05039      2 AINKKDLKLGELIGKGEFGDVMLGDYR--GQK---VAVKCLK--DDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdra 796
Cdd:cd05039     75 LYIVTEYMAKGSLVDYLRSRGRAVITrKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFG------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 eavyttmvrssllwphmllllsaiptgpmvyiLALPPslpglfplvvpCLSQPGsflrcggsGRSPALWAAPETLQFGHF 876
Cdd:cd05039    148 --------------------------------LAKEA-----------SSNQDG--------GKLPIKWTAPEALREKKF 176

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05039    177 STKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELDPAKRPTFKQLREKLE 254
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
 650-953 1.34e-63

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 216.16  E-value: 1.34e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGrqeLPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd05041      3 IGRGNFGDVYRGVLKPDN---TEVAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTTmvrssll 809
Cdd:cd05041     80 LLTFLRKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMS-REEEDGEYTV------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrCGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd05041    152 ---------------------------------------------SDGLKQIPIKWTAPEALNYGRYTSESDVWSFGILL 186

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  890 WEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05041    187 WEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPENRPSFSEIYNEL 250
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
 638-959 6.78e-62

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 211.90  E-value: 6.78e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRgNP 717
Cdd:cd05056      2 EIQREDITLGRCIGEGQFGDVYQGVYMSPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITE-NP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd05056     81 VWIVMELAPLGELRSYLQVNKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMVrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsGRSPALWAAPETLQFGHFS 877
Cdd:cd05056    161 SYYKASK------------------------------------------------------GKLPIKWMAPESINFRRFT 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKMG 957
Cdd:cd05056    187 SASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSKRPRFTELKAQLSDIL 266


                   ..
gi 1958775623  958 QE 959
Cdd:cd05056    267 QE 268
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 638-946 3.08e-60

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 207.26  E-value: 3.08e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQlpgrQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05068      4 EIDRKSLKLLRKLGSGQFGEVWEGLWN----NTTPVAVKTLKPGTMDPE--DFLREAQIMKKLRHPKLIQLYAVCTLEEP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd05068     78 IYIITELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVE 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSflrcggsgRSPALWAAPETLQFGHFS 877
Cdd:cd05068    158 DEYE---------------------------------------------AREGA--------KFPIKWTAPEAANYNRFS 184

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd05068    185 IKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIMLECWKADPMERPTF 253
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
 638-955 3.85e-59

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 204.62  E-value: 3.85e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCG-CLQL-PGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05049      1 HIKRDTIVLKRELGEGAFGKVFLGeCYNLePEQDKMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHH-------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLI 782
Cdd:cd05049     81 DPLLMVFEYMEHGDLNKFLRSHgpdaaflasedsaPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  783 CKISGFGRGpRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSP 862
Cdd:cd05049    161 VKIGDFGMS-RD----IYST------------------------------------------------DYYRVGGHTMLP 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  863 ALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGE 942
Cdd:cd05049    188 IRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQGRLLQRPRTCPSEVYAVMLGCWKREPQQ 267

                          330
                   ....*....|...
gi 1958775623  943 RPRFSQIHSILSK 955
Cdd:cd05049    268 RLNIKDIHKRLQE 280
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
 648-953 1.94e-58

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 202.26  E-value: 1.94e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGC---LQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEY 724
Cdd:cd05044      1 KFLGSGAFGEVFEGTakdILGDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILEL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  725 MNLGALDDFLRHHEAELVTAQLMGLLPGL------ASAMKYLSEMGYVHRGLAARRVLLSSglickisgfgRGPRDRaea 798
Cdd:cd05044     81 MEGGDLLSYLRAARPTAFTPPLLTLKDLLsicvdvAKGCVYLEDMHFVHRDLAARNCLVSS----------KDYRER--- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 vyttmvrssllwphmllllsaiptgpMVYIlalppslpGLFPLVVPCLSQpgSFLRCGGSGRSPALWAAPETLQFGHFSS 878
Cdd:cd05044    148 --------------------------VVKI--------GDFGLARDIYKN--DYYRKEGEGLLPVRWMAPESLVDGVFTT 191

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  879 ASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05044    192 QSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAGGRLDQPDNCPDDLYELMLRCWSTDPEERPSFARILEQL 266
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
 637-949 9.24e-58

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 200.31  E-value: 9.24e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  637 KELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQ--ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTR 714
Cdd:cd05036      1 KEVPRKNLTLIRALGQGAFGEVYEGTVSGMPGDpsPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  715 GNPLMIVTEYMNLGALDDFLRH------HEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSS---GLICKI 785
Cdd:cd05036     81 RLPRFILLELMAGGDLKSFLREnrprpeQPSSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCkgpGRVAKI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  786 SGFGRGpRDraeaVYttmvRSSllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsFLRCGGSGRSPALW 865
Cdd:cd05036    161 GDFGMA-RD----IY----RAD--------------------------------------------YYRKGGKAMLPVKW 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  866 AAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPR 945
Cdd:cd05036    188 MPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRMDPPKNCPGPVYRIMTQCWQHIPEDRPN 267


                   ....
gi 1958775623  946 FSQI 949
Cdd:cd05036    268 FSTI 271
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 639-953 1.86e-57

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 198.83  E-value: 1.86e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGclqlPGRQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05059      1 IDPSELTFLKELGSGQFGVVHLG----KWRGKIDVAIKMIKEGSMSED--DFIEEAKVMMKLSHPKLVQLYGVCTKQRPI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraea 798
Cdd:cd05059     75 FIVTEYMANGCLLNYLRERRGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFG--------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 vyttMVRssllwphmllllsaiptgpmvYILalppslpglfplvvpclsqpGSFLRCGGSGRSPALWAAPETLQFGHFSS 878
Cdd:cd05059    146 ----LAR---------------------YVL--------------------DDEYTSSVGTKFPVKWSPPEVFMYSKFSS 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  879 ASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05059    181 KSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPEERPTFKILLSQL 255
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
 648-953 8.94e-57

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 196.69  E-value: 8.94e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQlpgRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd05084      2 ERIGRGNFGEVFSGRLR---ADNTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTTMvrss 807
Cdd:cd05084     79 GDFLTFLRTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMS-REEEDGVYAAT---- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  808 llwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFGHFSSASDVWSFGI 887
Cdd:cd05084    154 ------------------------------------------------GGMKQIPVKWTAPEALNYGRYSSESDVWSFGI 185

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  888 VMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05084    186 LLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPRKRPSFSTVHQDL 251
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
 642-954 1.48e-56

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 197.94  E-value: 1.48e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  642 KSVTLEKsLGAGRFGD--LC-----CGCL--QLPGRQELP----VAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRL 708
Cdd:cd05051      6 KLEFVEK-LGEGQFGEvhLCeanglSDLTsdDFIGNDNKDepvlVAVKMLRPDASKNAREDFLKEVKIMSQLKDPNIVRL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  709 EGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLP-----------GLASAMKYLSEMGYVHRGLAARRVLL 777
Cdd:cd05051     85 LGVCTRDEPLCMIVEYMENGDLNQFLQKHEAETQGASATNSKTlsygtllymatQIASGMKYLESLNFVHRDLATRNCLV 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  778 SSGLICKISGFGrgprdraeavyttMVRSsllwphmllllsaiptgpmVYilalppslpglfplvvpclsqPGSFLRCGG 857
Cdd:cd05051    165 GPNYTIKIADFG-------------MSRN-------------------LY---------------------SGDYYRIEG 191

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  858 SGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFG-ERPYWDMSGQDVIKAVEDGFR-------LPPPRNCPSQLH 929
Cdd:cd05051    192 RAVLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTDEQVIENAGEFFRddgmevyLSRPPNCPKEIY 271

                          330       340
                   ....*....|....*....|....*
gi 1958775623  930 RLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05051    272 ELMLECWRRDEEDRPTFREIHLFLQ 296
EphR_LBD_A1 cd10479
Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the ...
 35-210 4.24e-55

Ligand Binding Domain of Ephrin type-A Receptor 1; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphA1 is downregulated in some advanced colorectal and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion.


Pssm-ID: 198447  Cd Length: 177  Bit Score: 189.09  E-value: 4.24e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTA-LPSTGWEEISGVdEHDRPIRTYQVCNVLEP-NQDNWLQTGWISRGR-GQRIFVELQFTLRD 111
Cdd:cd10479      1 EVTLMDTSTAQGELGWLLdPPEVGWSEVQQM-LNGTPLYMYQDCPVQSEgDTDHWLRSNWIYRGEeASRIYVELQFTVRD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  112 CSSIPGATG--TCKETFNAYYLETEADLGrghphLGGNRP--RKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQG 187
Cdd:cd10479     80 CKSFPGGAGplGCKETFNLYYMESDQDVG-----IQLRRPlfQKVTTVAADQSFTIRDLASGSVKLNVERCSLGKLTRRG 154

                          170       180
                   ....*....|....*....|...
gi 1958775623  188 FHLAFQDVGACVALVSVRVYYKQ 210
Cdd:cd10479    155 LYLAFHNPGACVALVSVRVFYQR 177
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
 636-953 2.89e-54

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 190.25  E-value: 2.89e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  636 AKELDAKSVTLEKSLGAGRFGDLCCGCLQlpgrQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05072      1 AWEIPRESIKLVKKLGAGQFGEVWMGYYN----NSTKVAVKTLKPGTMSVQ--AFLEEANLMKTLQHDKLVRLYAVVTKE 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHE-AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRD 794
Cdd:cd05072     75 EPIYIITEYMAKGSLLDFLKSDEgGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLA-RV 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflRCGGsgRSPALWAAPETLQFG 874
Cdd:cd05072    154 IEDNEYTA---------------------------------------------------REGA--KFPIKWTAPEAINFG 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05072    181 SFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKTCWKEKAEERPTFDYLQSVL 259
EphR_LBD_B4 cd10474
Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the ...
 35-210 1.04e-53

Ligand Binding Domain of Ephrin type-B Receptor 4; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB4 plays a role in osteoblast differentiation and has been linked to multiple myeloma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198442  Cd Length: 180  Bit Score: 185.16  E-value: 1.04e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTG--WEEISGVDEHDRPIRTYQVCNV-LEPNQDNWLQTGWISRGRGQRIFVELQFTLRD 111
Cdd:cd10474      1 EETLLNTKLETADLKWVTYPQVDgqWEELSGLDEEQHSVRTYEVCDAqRAGGQAHWLRTGWVPRRGAVHVYATLRFTMLE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  112 CSSIPGATGTCKETFNAYYLETEADLGRGH-PHLGGNRPRKIDTIAADESFTQGDLGERKMKLNTEVREIGPLSRQGFHL 190
Cdd:cd10474     81 CLSLPRAGRSCKETFTVFYYESDADTATAHtPAWMENPYIKVDTVAAEHLTRKRPGAEATGKVNVKTLRLGPLSKAGFYL 160

                          170       180
                   ....*....|....*....|
gi 1958775623  191 AFQDVGACVALVSVRVYYKQ 210
Cdd:cd10474    161 AFQDQGACMALLSLHLFYKK 180
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
 648-960 2.69e-53

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 188.01  E-value: 2.69e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQ-ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTrGNPLMIVTEYMN 726
Cdd:cd05057     13 KVLGSGAFGTVYKGVWIPEGEKvKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICL-SSQVQLITQLMP 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrs 806
Cdd:cd05057     92 LGCLLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFG----------------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 sllwphmllLLSAIPTGPMVYILAlppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd05057    155 ---------LAKLLDVDEKEYHAE---------------------------GGKVPIKWMALESIQYRIYTHKSDVWSYG 198

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  887 IVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKMGQEP 960
Cdd:cd05057    199 VTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDVYMVLVKCWMIDAESRPTFKELANEFSKMARDP 272
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
 648-954 3.67e-53

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 186.78  E-value: 3.67e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKL--SFLAEALTLGQFDHSHIVRLEGVVtRGNPLMIVTEYM 725
Cdd:cd05040      1 EKLGDGSFGVVRRGEWTTPSGKVIQVAVKCLKSDVLSQPNAmdDFLKEVNAMHSLDHPNLIRLYGVV-LSSPLMMVTELA 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttMVR 805
Cdd:cd05040     80 PLGSLLDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFG-------------LMR 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  806 ssllwphmllllsAIPTGPMVYILALPPSLPglFPlvvpclsqpgsflrcggsgrspalWAAPETLQFGHFSSASDVWSF 885
Cdd:cd05040    147 -------------ALPQNEDHYVMQEHRKVP--FA------------------------WCAPESLKTRKFSHASDVWMF 187

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  886 GIVMWEVMAFGERPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05040    188 GVTLWEMFTYGEEPWLGLNGSQILEKIDkEGERLERPDDCPQDIYNVMLQCWAHKPADRPTFVALRDFLP 257
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
 650-954 4.86e-53

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 185.98  E-value: 4.86e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLqlpgRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd05085      4 LGKGNFGEVYKGTL----KDKTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTTmvrssll 809
Cdd:cd05085     80 FLSFLRKKKDELKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMS-RQEDDGVYSS------- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd05085    152 ----------------------------------------------SGLKQIPIKWTAPEALNYGRYSSESDVWSFGILL 185

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  890 WEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05085    186 WETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRPKFSELQKELA 250
EphR_LBD_B6 cd10475
Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the ...
 35-208 5.82e-53

Ligand Binding Domain of Ephrin type-B Receptor 6; Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. EphB6, a kinase-defective member of this family, is downregulated in MDA-MB-231-breast cancer cells and myeloid cancers and upregulated in neuroblasoma and glioblastoma. EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling).


Pssm-ID: 198443  Cd Length: 180  Bit Score: 183.21  E-value: 5.82e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   35 EVTLLDSKASQAELGWTALPSTGWEEISGVDEHDRPIRTYQVCNV--LEPNQDNWLQTGWISRGRGQRIFVELQFTLRDC 112
Cdd:cd10475      1 EEVLLDTTGETSEIGWLTYPPGGWDEVSVLDDQRRLTRTFEVCNVaaQGPGQDNWLRTHFIERRGAHRVHVRLHFSVRDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  113 SSIPGATGTCKETFNAYYLETEADLGRGHP---HLGgnRPRKIDTIAADESFTQGDLGERK-MKLNTEVREIGPLSRQGF 188
Cdd:cd10475     81 ASLGVPGGTCRETFTLYYRQADEPDEPADKsewHEG--PWTKVDTIAADESFPASLGKGGQgLQMNVKERSFGPLTQRGF 158

                          170       180
                   ....*....|....*....|
gi 1958775623  189 HLAFQDVGACVALVSVRVYY 208
Cdd:cd10475    159 YLAFQDSGACLSLVAVKVFF 178
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
 638-955 1.60e-52

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 185.81  E-value: 1.60e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLccgcLQ------LPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGV 711
Cdd:cd05050      1 EYPRNNIEYVRDIGQGAFGRV----FQarapglLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGV 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  712 VTRGNPLMIVTEYMNLGALDDFLRHHEA---------------------ELVTAQLMGLLPGLASAMKYLSEMGYVHRGL 770
Cdd:cd05050     77 CAVGKPMCLLFEYMAYGDLNEFLRHRSPraqcslshstssarkcglnplPLSCTEQLCIAKQVAAGMAYLSERKFVHRDL 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  771 AARRVLLSSGLICKISGFGRgprdrAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpg 850
Cdd:cd05050    157 ATRNCLVGENMVVKIADFGL-----SRNIYSA------------------------------------------------ 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  851 SFLRCGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHR 930
Cdd:cd05050    184 DYYKASENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIYYVRDGNVLSCPDNCPLELYN 263

                          330       340
                   ....*....|....*....|....*
gi 1958775623  931 LMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05050    264 LMRLCWSKLPSDRPSFASINRILQR 288
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
 638-953 3.11e-52

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 184.89  E-value: 3.11e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELP--VAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05048      1 EIPLSAVRFLEELGEGAFGKVYKGELLGPSSEESAisVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFL-RHHEAELVTAQLMG------LLPG--------LASAMKYLSEMGYVHRGLAARRVLLSSG 780
Cdd:cd05048     81 QPQCMLFEYMAHGDLHEFLvRHSPHSDVGVSSDDdgtassLDQSdflhiaiqIAAGMEYLSSHHYVHRDLAARNCLVGDG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  781 LICKISGFGRGpRDRAEAVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsQPGSFLrcggsgr 860
Cdd:cd05048    161 LTVKISDFGLS-RDIYSSDYYRV--------------------------------------------QSKSLL------- 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  861 sPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDP 940
Cdd:cd05048    189 -PVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQLLPCPEDCPARVYSLMVECWHEIP 267

                          330
                   ....*....|...
gi 1958775623  941 GERPRFSQIHSIL 953
Cdd:cd05048    268 SRRPRFKEIHTRL 280
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
 638-954 4.05e-52

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 183.79  E-value: 4.05e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLqlpgRQELPVAVHTLREGCSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRGNP 717
Cdd:cd05148      2 ERPREEFTLERKLGSGYFGEVWEGLW----KNRVRVAIKILKSDDLLKQQ-DFQKEVQALKRLRHKHLISLFAVCSVGEP 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAE-LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRA 796
Cdd:cd05148     77 VYIITELMEKGSLLAFLRSPEGQvLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLA-RLIK 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 EAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGHF 876
Cdd:cd05148    156 EDVYLS------------------------------------------------------SDKKIPYKWTAPEAASHGTF 181

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05148    182 STKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLECWAAEPEDRPSFKALREELD 259
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
 638-953 6.13e-52

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 183.55  E-value: 6.13e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQlpGRQElpVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRgNP 717
Cdd:cd05067      3 EVPRETLKLVERLGAGQFGEVWMGYYN--GHTK--VAIKSLKQGSMSPD--AFLAEANLMKQLQHQRLVRLYAVVTQ-EP 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEA-ELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRA 796
Cdd:cd05067     76 IYIITEYMENGSLVDFLKTPSGiKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLA-RLIE 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 EAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSflrcggsgRSPALWAAPETLQFGHF 876
Cdd:cd05067    155 DNEYT---------------------------------------------AREGA--------KFPIKWTAPEAINYGTF 181

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05067    182 TIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLMRLCWKERPEDRPTFEYLRSVL 258
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
 639-956 1.97e-51

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 181.61  E-value: 1.97e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGclQLPGRqelPVAVHTLRegCsDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRgNPL 718
Cdd:cd05083      3 LNLQKLTLGEIIGEGEFGAVLQG--EYMGQ---KVAVKNIK--C-DVTAQAFLEETAVMTKLQHKNLVRLLGVILH-NGL 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELV-TAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdrae 797
Cdd:cd05083     74 YIVMELMSKGNLVNFLRSRGRALVpVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFG-------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 avyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSflRCGGSGRSPALWAAPETLQFGHFS 877
Cdd:cd05083    146 ------------------------------------------------LAKVGS--MGVDNSRLPVKWTAPEALKNKKFS 175

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05083    176 SKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAEPGKRPSFKKLREKLEKE 254
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
 638-956 7.18e-51

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 180.31  E-value: 7.18e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQlpgRQELPVAVHTLREgcsDSQKLS-FLAEALTLGQFDHSHIVRLEGVVTRGN 716
Cdd:cd05052      2 EIERTDITMKHKLGGGQYGEVYEGVWK---KYNLTVAVKTLKE---DTMEVEeFLKEAAVMKEIKHPNLVQLLGVCTREP 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  717 PLMIVTEYMNLGALDDFLRHHEAELVTA-QLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDR 795
Cdd:cd05052     76 PFYIITEFMPYGNLLDYLRECNREELNAvVLLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLS-RLM 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 AEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSflrcggsgRSPALWAAPETLQFGH 875
Cdd:cd05052    155 TGDTYT---------------------------------------------AHAGA--------KFPIKWTAPESLAYNK 181

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  876 FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05052    182 FSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPSDRPSFAEIHQALET 261


                   .
gi 1958775623  956 M 956
Cdd:cd05052    262 M 262
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
 642-953 1.56e-50

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 180.16  E-value: 1.56e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  642 KSVTLEKSLGAGRFGDLC---CGCLqLPGRQELPVAVHTLREGcSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05092      5 RDIVLKWELGEGAFGKVFlaeCHNL-LPEQDKMLVAVKALKEA-TESARQDFQREAELLTVLQHQHIVRFYGVCTEGEPL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHE--------------AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICK 784
Cdd:cd05092     83 IMVFEYMRHGDLNRFLRSHGpdakildggegqapGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVK 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  785 ISGFGRGpRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPAL 864
Cdd:cd05092    163 IGDFGMS-RD----IYST------------------------------------------------DYYRVGGRTMLPIR 189

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd05092    190 WMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELERPRTCPPEVYAIMQGCWQREPQQRH 269


                   ....*....
gi 1958775623  945 RFSQIHSIL 953
Cdd:cd05092    270 SIKDIHSRL 278
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 648-953 1.92e-50

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 178.57  E-value: 1.92e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRqelpVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRgNPLMIVTEYMNL 727
Cdd:cd14203      1 VKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMSPE--AFLEEAQIMKKLRHDKLVQLYAVVSE-EPIYIVTEFMSK 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEAE-LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttMVRs 806
Cdd:cd14203     74 GSLLDFLKDGEGKyLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFG-------------LAR- 139

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 sllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLRCGGSgRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd14203    140 ---------------------------------------LIEDNEYTARQGA-KFPIKWTAPEAALYGRFTIKSDVWSFG 179

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  887 IVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd14203    180 ILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTFEYLQSFL 246
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
 638-953 1.79e-49

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 177.08  E-value: 1.79e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQ--LPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05061      2 EVSREKITLLRELGQGSFGMVYEGNARdiIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLR--HHEAELVTA-------QLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKIS 786
Cdd:cd05061     82 QPTLVVMELMAHGDLKSYLRslRPEAENNPGrppptlqEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  787 GFGRgPRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPALWA 866
Cdd:cd05061    162 DFGM-TRD----IYET------------------------------------------------DYYRKGGKGLLPVRWM 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd05061    189 APESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTF 268


                   ....*..
gi 1958775623  947 SQIHSIL 953
Cdd:cd05061    269 LEIVNLL 275
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
 636-953 1.24e-48

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 174.06  E-value: 1.24e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  636 AKELDAKSVTLEKSLGAGRFGDLCCGCLQlpgrQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRg 715
Cdd:cd05073      5 AWEIPRESLKLEKKLGAGQFGEVWMATYN----KHTKVAVKTMKPGSMSVE--AFLAEANVMKTLQHDKLVKLHAVVTK- 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRD 794
Cdd:cd05073     78 EPIYIITEFMAKGSLLDFLKSDEGSKQPlPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLA-RV 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflRCGGsgRSPALWAAPETLQFG 874
Cdd:cd05073    157 IEDNEYTA---------------------------------------------------REGA--KFPIKWTAPEAINFG 183

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05073    184 SFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVL 262
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
 638-962 7.24e-48

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 172.18  E-value: 7.24e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQlpgrQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRgNP 717
Cdd:cd05070      5 EIPRESLQLIKRLGNGQFGEVWMGTWN----GNTKVAIKTLKPGTMSPE--SFLEEAQIMKKLKHDKLVQLYAVVSE-EP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAE-LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRA 796
Cdd:cd05070     78 IYIVTEYMSKGSLLDFLKDGEGRaLKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLA-RLIE 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 EAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSFlrcggsgrsPALWAAPETLQFGHF 876
Cdd:cd05070    157 DNEYTA--------------------------------------------RQGAKF---------PIKWTAPEAALYGRF 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05070    184 TIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLEDY 263


                   ....*.
gi 1958775623  957 GQEPEP 962
Cdd:cd05070    264 FTATEP 269
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
 643-958 2.13e-47

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 171.38  E-value: 2.13e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  643 SVTLEKSLGAGRFGDLCCG-CLQL-PGRQELPVAVHTLREGcSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMI 720
Cdd:cd05093      6 NIVLKRELGEGAFGKVFLAeCYNLcPEQDKILVAVKTLKDA-SDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIM 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  721 VTEYMNLGALDDFLRHH------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGF 788
Cdd:cd05093     85 VFEYMKHGDLNKFLRAHgpdavlmaegnrPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDF 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  789 GRGpRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPALWAAP 868
Cdd:cd05093    165 GMS-RD----VYST------------------------------------------------DYYRVGGHTMLPIRWMPP 191

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  869 ETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQ 948
Cdd:cd05093    192 ESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHMRLNIKE 271

                          330
                   ....*....|
gi 1958775623  949 IHSILSKMGQ 958
Cdd:cd05093    272 IHSLLQNLAK 281
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
 639-949 3.87e-47

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 169.36  E-value: 3.87e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQlpgrQELPVAVHTLREGCSDSQKlsFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05112      1 IDPSELTFVQEIGSGQFGLVHLGYWL----NKDKVAIKTIREGAMSEED--FIEEAEVMMKLSHPKLVQLYGVCLEQAPI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraea 798
Cdd:cd05112     75 CLVFEFMEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFG--------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 vyttMVRssllwphmllllsaiptgpmvyilalppslpglFPLVVPCLSQPGSflrcggsgRSPALWAAPETLQFGHFSS 878
Cdd:cd05112    146 ----MTR---------------------------------FVLDDQYTSSTGT--------KFPVKWSSPEVFSFSRYSS 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  879 ASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05112    181 KSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERPEDRPSFSLL 251
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
 648-953 4.99e-47

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 169.87  E-value: 4.99e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPG-RQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTR--GNPLMIVTEY 724
Cdd:cd05038     10 KQLGEGHFGSVELCRYDPLGdNTGEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESpgRRSLRLIMEY 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  725 MNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmv 804
Cdd:cd05038     90 LPSGSLRDYLQRHRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFG--------------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  805 rssllwphmllLLSAIPTGPMVYILALPpslpglfplvvpclsqpgsflrcggsGRSPALWAAPETLQFGHFSSASDVWS 884
Cdd:cd05038    155 -----------LAKVLPEDKEYYYVKEP--------------------------GESPIFWYAPECLRESRFSSASDVWS 197

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  885 FGIVMWEVMAFGE------RPYWDMSGQ--------DVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIH 950
Cdd:cd05038    198 FGVTLYELFTYGDpsqsppALFLRMIGIaqgqmivtRLLELLKSGERLPRPPSCPDEVYDLMKECWEYEPQDRPSFSDLI 277


                   ...
gi 1958775623  951 SIL 953
Cdd:cd05038    278 LII 280
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
 648-949 8.97e-47

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 168.22  E-value: 8.97e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPgRQELPVAVHTLREGCSD-SQKLSFLAEALTLGQFDHSHIVRLEGVVtRGNPLMIVTEYMN 726
Cdd:cd05116      1 GELGSGNFGTVKKGYYQMK-KVVKTVAVKILKNEANDpALKDELLREANVMQQLDNPYIVRMIGIC-EAESWMLVMEMAE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLR-------HHEAELVTAQLMGllpglasaMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeav 799
Cdd:cd05116     79 LGPLNKFLQknrhvteKNITELVHQVSMG--------MKYLEESNFVHRDLAARNVLLVTQHYAKISDFG---------- 140

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  800 yttmvrssllwphmllllsaiptgpmvyilalppslpglfplVVPCLSQPGSFLRCGGSGRSPALWAAPETLQFGHFSSA 879
Cdd:cd05116    141 ------------------------------------------LSKALRADENYYKAQTHGKWPVKWYAPECMNYYKFSSK 178

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  880 SDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05116    179 SDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDVDERPGFAAV 248
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
 650-953 4.67e-46

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 165.79  E-value: 4.67e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQlpGRqelPVAVHTLREGCSDSQKLS-FLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLG 728
Cdd:cd13999      1 IGSGSFGEVYKGKWR--GT---DVAIKKLKVEDDNDELLKeFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGG 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  729 ALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG--RgprdraEAVYTTMVRS 806
Cdd:cd13999     76 SLYDLLHKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGlsR------IKNSTTEKMT 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 SLlwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrCGgsgrSPAlWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd13999    150 GV----------------------------------------------VG----TPR-WMAPEVLRGEPYTEKADVYSFG 178

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  887 IVMWEvMAFGERPYWDMSG-QDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd13999    179 IVLWE-LLTGEVPFKELSPiQIAAAVVQKGLRPPIPPDCPPELSKLIKRCWNEDPEKRPSFSEIVKRL 245
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 637-953 7.33e-46

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 166.73  E-value: 7.33e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  637 KELDAKSVTLEKSLGAGRFGDLCCGCL--QLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTR 714
Cdd:cd05091      1 KEINLSAVRFMEELGEDRFGKVYKGHLfgTAPGEQTQAVAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  715 GNPLMIVTEYMNLGALDDFL---------------RHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSS 779
Cdd:cd05091     81 EQPMSMIFSYCSHGDLHEFLvmrsphsdvgstdddKTVKSTLEPADFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  780 GLICKISGFGRGPRDRAEAVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSG 859
Cdd:cd05091    161 KLNVKISDLGLFREVYAADYYKLM-----------------------------------------------------GNS 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  860 RSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKD 939
Cdd:cd05091    188 LLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIRNRQVLPCPDDCPAWVYTLMLECWNEF 267

                          330
                   ....*....|....
gi 1958775623  940 PGERPRFSQIHSIL 953
Cdd:cd05091    268 PSRRPRFKDIHSRL 281
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
 642-958 2.05e-45

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 165.57  E-value: 2.05e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  642 KSVTLEKSLGAGRFGDLCCG-CLQL-PGRQELPVAVHTLREGCSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRGNPLM 719
Cdd:cd05094      5 RDIVLKRELGEGAFGKVFLAeCYNLsPTKDKMLVAVKTLKDPTLAARK-DFQREAELLTNLQHDHIVKFYGVCGDGDPLI 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  720 IVTEYMNLGALDDFLRHH---------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICK 784
Cdd:cd05094     84 MVFEYMKHGDLNKFLRAHgpdamilvdgqprqaKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLLVK 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  785 ISGFGRGpRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPAL 864
Cdd:cd05094    164 IGDFGMS-RD----VYST------------------------------------------------DYYRVGGHTMLPIR 190

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd05094    191 WMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQGRVLERPRVCPKEVYDIMLGCWQREPQQRL 270

                          330
                   ....*....|....
gi 1958775623  945 RFSQIHSILSKMGQ 958
Cdd:cd05094    271 NIKEIYKILHALGK 284
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
 647-949 2.32e-45

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 164.73  E-value: 2.32e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  647 EKSLGAGRFGDLCCGCLQLPGRQeLPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVtRGNPLMIVTEYMN 726
Cdd:cd05115      9 EVELGSGNFGCVKKGVYKMRKKQ-IDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVC-EAEALMLVMEMAS 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrs 806
Cdd:cd05115     87 GGPLNKFLSGKKDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFG----------------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 sllwphmllllsaiptgpmvyilalppslpglfplVVPCLSQPGSFLRCGGSGRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd05115    150 -----------------------------------LSKALGADDSYYKARSAGKWPLKWYAPECINFRKFSSRSDVWSYG 194

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  887 IVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05115    195 VTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKWEDRPNFLTV 257
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
 646-956 2.68e-45

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 165.14  E-value: 2.68e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGDLCCG-CLQLPGRQELP-VAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd05045      4 LGKTLGEGEFGKVVKAtAFRLKGRAGYTtVAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLR-------------------HHEAELVTAQLMGLLPGLA----SAMKYLSEMGYVHRGLAARRVLLSSG 780
Cdd:cd05045     84 YAKYGSLRSFLResrkvgpsylgsdgnrnssYLDNPDERALTMGDLISFAwqisRGMQYLAEMKLVHRDLAARNVLVAEG 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  781 LICKISGFGRGpRDraeavyttmvrssllwphmllllsaiptgpmVYilalppslpglfplvvpclsQPGSFLRcGGSGR 860
Cdd:cd05045    164 RKMKISDFGLS-RD-------------------------------VY--------------------EEDSYVK-RSKGR 190

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  861 SPALWAAPETLqFGH-FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKD 939
Cdd:cd05045    191 IPVKWMAIESL-FDHiYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTGYRMERPENCSEEMYNLMLTCWKQE 269

                          330
                   ....*....|....*..
gi 1958775623  940 PGERPRFSQIHSILSKM 956
Cdd:cd05045    270 PDKRPTFADISKELEKM 286
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
 639-953 1.43e-44

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 162.07  E-value: 1.43e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGclqlpGRQELPVAVHTLRegcSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGN-P 717
Cdd:cd05082      3 LNMKELKLLQTIGKGEFGDVMLG-----DYRGNKVAVKCIK---NDATAQAFLAEASVMTQLRHSNLVQLLGVIVEEKgG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQ-LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdra 796
Cdd:cd05082     75 LYIVTEYMAKGSLVDYLRSRGRSVLGGDcLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFG------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 eavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLRcgGSGRSPALWAAPETLQFGHF 876
Cdd:cd05082    148 -------------------------------------------------LTKEASSTQ--DTGKLPVKWTAPEALREKKF 176

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05082    177 STKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLDAAMRPSFLQLREQL 253
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 638-953 4.33e-44

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 161.72  E-value: 4.33e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQLPGR-QELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGN 716
Cdd:cd05090      1 ELPLSAVRFMEELGECAFGKIYKGHLYLPGMdHAQLVAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGVVTQEQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  717 PLMIVTEYMNLGALDDFL----RHHE------------AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSG 780
Cdd:cd05090     81 PVCMLFEFMNQGDLHEFLimrsPHSDvgcssdedgtvkSSLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQ 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  781 LICKISGFGRGpRDRAEAVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsQPGSFLrcggsgr 860
Cdd:cd05090    161 LHVKISDLGLS-REIYSSDYYRV--------------------------------------------QNKSLL------- 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  861 sPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDP 940
Cdd:cd05090    189 -PIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQLLPCSEDCPPRMYSLMTECWQEIP 267

                          330
                   ....*....|...
gi 1958775623  941 GERPRFSQIHSIL 953
Cdd:cd05090    268 SRRPRFKDIHARL 280
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
 636-962 7.96e-44

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 160.62  E-value: 7.96e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  636 AKELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRqelpVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRg 715
Cdd:cd05069      6 AWEIPRESLRLDVKLGQGCFGEVWMGTWNGTTK----VAIKTLKPGTMMPE--AFLQEAQIMKKLRHDKLVPLYAVVSE- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAE-LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRD 794
Cdd:cd05069     79 EPIYIVTEFMGKGSLLDFLKEGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLA-RL 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSFlrcggsgrsPALWAAPETLQFG 874
Cdd:cd05069    158 IEDNEYTA--------------------------------------------RQGAKF---------PIKWTAPEAALYG 184

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05069    185 RFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHELMKLCWKKDPDERPTFEYIQSFLE 264


                   ....*...
gi 1958775623  955 KMGQEPEP 962
Cdd:cd05069    265 DYFTATEP 272
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
 638-953 8.38e-44

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 161.31  E-value: 8.38e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGD--LCCG-----------CLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSH 704
Cdd:cd05095      1 EFPRKLLTFKEKLGEGQFGEvhLCEAegmekfmdkdfALEVSENQPVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  705 IVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPG-----------LASAMKYLSEMGYVHRGLAAR 773
Cdd:cd05095     81 IIRLLAVCITDDPLCMITEYMENGDLNQFLSRQQPEGQLALPSNALTVsysdlrfmaaqIASGMKYLSSLNFVHRDLATR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  774 RVLLSSGLICKISGFGrgprdraeavyttMVRSsllwphmllllsaiptgpmVYilalppslpglfplvvpclsqPGSFL 853
Cdd:cd05095    161 NCLVGKNYTIKIADFG-------------MSRN-------------------LY---------------------SGDYY 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  854 RCGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAF-GERPYWDMSGQDVIKAVEDGFR-------LPPPRNCP 925
Cdd:cd05095    188 RIQGRAVLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQPYSQLSDEQVIENTGEFFRdqgrqtyLPQPALCP 267

                          330       340
                   ....*....|....*....|....*...
gi 1958775623  926 SQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05095    268 DSVYKLMLSCWRRDTKDRPSFQEIHTLL 295
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
 639-949 1.12e-43

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 159.28  E-value: 1.12e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGclqlPGRQELPVAVHTLREGcSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05113      1 IDPKDLTFLKELGTGQFGVVKYG----KWRGQYDVAIKMIKEG-SMSED-EFIEEAKVMMNLSHEKLVQLYGVCTKQRPI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEA 798
Cdd:cd05113     75 FIITEYMANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLS-RYVLDD 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 VYTTMVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsgRSPALWAAPETLQFGHFSS 878
Cdd:cd05113    154 EYTSSVGS-----------------------------------------------------KFPVRWSPPEVLMYSKFSS 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  879 ASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05113    181 KSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKIL 251
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
 638-956 1.74e-43

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 160.28  E-value: 1.74e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCG-CLQLPGRQELP--VAVHTLREGCSDSQKLSFLAEALTL---GQfdHSHIVRLEGV 711
Cdd:cd05053      8 ELPRDRLTLGKPLGEGAFGQVVKAeAVGLDNKPNEVvtVAVKMLKDDATEKDLSDLVSEMEMMkmiGK--HKNIINLLGA 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  712 VTRGNPLMIVTEYMNLGALDDFLRHH---------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVL 776
Cdd:cd05053     86 CTQDGPLYVVVEYASKGNLREFLRARrppgeeaspddprvpEEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVL 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  777 LSSGLICKISGFGRGpRDraeavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvVPCLSqpgsFLRCG 856
Cdd:cd05053    166 VTEDNVMKIADFGLA-RD------------------------------------------------IHHID----YYRKT 192

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  857 GSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECW 936
Cdd:cd05053    193 TNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMEKPQNCTQELYMLMRDCW 272

                          330       340
                   ....*....|....*....|
gi 1958775623  937 QKDPGERPRFSQIHSILSKM 956
Cdd:cd05053    273 HEVPSQRPTFKQLVEDLDRI 292
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
 648-955 4.33e-43

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 158.40  E-value: 4.33e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLP--GRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd05046     11 TTLGRGEFGEVFLAKAKGIeeEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRHHEAE--------LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAE 797
Cdd:cd05046     91 DLGDLKQFLRATKSKdeklkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLS-KDVYN 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMVRssllwphmllllsaiptgpmvyilalppslpglfpLVVPclsqpgsfLRcggsgrspalWAAPETLQFGHFS 877
Cdd:cd05046    170 SEYYKLRN-----------------------------------ALIP--------LR----------WLAPEAVQEDDFS 196

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  878 SASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDG-FRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05046    197 TKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGkLELPVPEGCPSRLYKLMTRCWAVNPKDRPSFSELVSALGE 275
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
 636-962 1.73e-42

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 156.77  E-value: 1.73e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  636 AKELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRqelpVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRg 715
Cdd:cd05071      3 AWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTR----VAIKTLKPGTMSPE--AFLQEAQVMKKLRHEKLVQLYAVVSE- 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRD 794
Cdd:cd05071     76 EPIYIVTEYMSKGSLLDFLKGEMGKYLRlPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLA-RL 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSFlrcggsgrsPALWAAPETLQFG 874
Cdd:cd05071    155 IEDNEYTA--------------------------------------------RQGAKF---------PIKWTAPEAALYG 181

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05071    182 RFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLE 261


                   ....*...
gi 1958775623  955 KMGQEPEP 962
Cdd:cd05071    262 DYFTSTEP 269
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
 639-949 2.67e-42

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 155.40  E-value: 2.67e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGclqlPGRQELPVAVHTLREGCSDSQklSFLAEALTLGQFDHSHIVRLEGVVTRGNPL 718
Cdd:cd05114      1 INPSELTFMKELGSGLFGVVRLG----KWRAQYKVAIKAIREGAMSEE--DFIEEAKVMMKLTHPKLVQLYGVCTQQKPI 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraea 798
Cdd:cd05114     75 YIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFG--------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 vyttMVRssllwphmllllsaiptgpmvYILalppslpglfplvvpclsqPGSFLRCGGSgRSPALWAAPETLQFGHFSS 878
Cdd:cd05114    146 ----MTR---------------------YVL-------------------DDQYTSSSGA-KFPVKWSPPEVFNYSKFSS 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  879 ASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05114    181 KSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGRPTFADL 251
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
 638-949 1.44e-41

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 154.04  E-value: 1.44e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCCGCLQ--LPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05062      2 EVAREKITMSRELGQGSFGMVYEGIAKgvVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLP---------GLASAMKYLSEMGYVHRGLAARRVLLSSGLICKIS 786
Cdd:cd05062     82 QPTLVIMELMTRGDLKSYLRSLRPEMENNPVQAPPSlkkmiqmagEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  787 GFGRgPRDraeaVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFLRCGGSGRSPALWA 866
Cdd:cd05062    162 DFGM-TRD----IYET------------------------------------------------DYYRKGGKGLLPVRWM 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd05062    189 SPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSF 268


                   ...
gi 1958775623  947 SQI 949
Cdd:cd05062    269 LEI 271
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
 648-960 1.62e-41

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 153.96  E-value: 1.62e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQ-ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTrGNPLMIVTEYMN 726
Cdd:cd05111     13 KVLGSGVFGTVHKGIWIPEGDSiKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICP-GASLQLVTQLLP 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRG---PRDRAEAVYTTM 803
Cdd:cd05111     92 LGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVAdllYPDDKKYFYSEA 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  804 vrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsgRSPALWAAPETLQFGHFSSASDVW 883
Cdd:cd05111    172 --------------------------------------------------------KTPIKWMALESIHFGKYTHQSDVW 195

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  884 SFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKMGQEP 960
Cdd:cd05111    196 SYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDP 272
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
 644-954 1.96e-40

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 150.68  E-value: 1.96e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTR-GNPLMIVT 722
Cdd:cd05043      8 VTLSDLLQEGTFGRIFHGILRDEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCIEdGEKPMVLY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFL---RHHEAE----LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISgfgrgprDR 795
Cdd:cd05043     88 PYMNWGNLKLFLqqcRLSEANnpqaLSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKIT-------DN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 AeavyttMVRSsllwphmllllsaiptgpmvyilalppslpgLFPLVVPCLsqpgsflrcGGSGRSPALWAAPETLQFGH 875
Cdd:cd05043    161 A------LSRD-------------------------------LFPMDYHCL---------GDNENRPIKWMSLESLVNKE 194

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  876 FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05043    195 YSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINCPDELFAVMACCWALDPEERPSFQQLVQCLT 273
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
 646-955 2.06e-40

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 151.63  E-value: 2.06e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGD--LCcgclQLPGRQELP---------------VAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRL 708
Cdd:cd05096      9 FKEKLGEGQFGEvhLC----EVVNPQDLPtlqfpfnvrkgrpllVAVKILRPDANKNARNDFLKEVKILSRLKDPNIIRL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  709 EGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQ------------------LMGLLPGLASAMKYLSEMGYVHRGL 770
Cdd:cd05096     85 LGVCVDEDPLCMITEYMENGDLNQFLSSHHLDDKEENgndavppahclpaisyssLLHVALQIASGMKYLSSLNFVHRDL 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  771 AARRVLLSSGLICKISGFGrgprdraeavyttMVRSsllwphmllllsaiptgpmVYilalppslpglfplvvpclsqPG 850
Cdd:cd05096    165 ATRNCLVGENLTIKIADFG-------------MSRN-------------------LY---------------------AG 191

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  851 SFLRCGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEV-MAFGERPYWDMSGQDVIKAVEDGFR-------LPPPR 922
Cdd:cd05096    192 DYYRIQGRAVLPIRWMAWECILMGKFTTASDVWAFGVTLWEIlMLCKEQPYGELTDEQVIENAGEFFRdqgrqvyLFRPP 271

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1958775623  923 NCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd05096    272 PCPQGLYELMLQCWSRDCRERPSFSDIHAFLTE 304
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
 642-956 1.39e-39

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 148.99  E-value: 1.39e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  642 KSVTLEKSLGAGRFGDLCCGCLQLPGrQELPVAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVVTRGNPLMI 720
Cdd:cd05089      2 EDIKFEDVIGEGNFGQVIKAMIKKDG-LKMNAAIKMLKEFASENDHRDFAGELEVLCKLgHHPNIINLLGACENRGYLYI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  721 VTEYMNLGALDDFLR--------------HHEAELVTA-QLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKI 785
Cdd:cd05089     81 AIEYAPYGNLLDFLRksrvletdpafakeHGTASTLTSqQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  786 SGFGRgprDRAEAVYT--TMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsGRSPA 863
Cdd:cd05089    161 ADFGL---SRGEEVYVkkTM-------------------------------------------------------GRLPV 182

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  864 LWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd05089    183 RWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDDEVYELMRQCWRDRPYER 262

                          330
                   ....*....|...
gi 1958775623  944 PRFSQIHSILSKM 956
Cdd:cd05089    263 PPFSQISVQLSRM 275
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
 638-953 3.30e-39

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 147.82  E-value: 3.30e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGD--LC--CGCLQLPGR-------QELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIV 706
Cdd:cd05097      1 EFPRQQLRLKEKLGEGQFGEvhLCeaEGLAEFLGEgapefdgQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNII 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  707 RLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAE-----------LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRV 775
Cdd:cd05097     81 RLLGVCVSDDPLCMITEYMENGDLNQFLSQREIEstfthannipsVSIANLLYMAVQIASGMKYLASLNFVHRDLATRNC 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  776 LLSSGLICKISGFGrgprdraeavyttMVRSsllwphmllllsaiptgpmVYilalppslpglfplvvpclsqPGSFLRC 855
Cdd:cd05097    161 LVGNHYTIKIADFG-------------MSRN-------------------LY---------------------SGDYYRI 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  856 GGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAF-GERPYWDMSGQDVIKAVEDGFR-------LPPPRNCPSQ 927
Cdd:cd05097    188 QGRAVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQVIENTGEFFRnqgrqiyLSQTPLCPSP 267

                          330       340
                   ....*....|....*....|....*.
gi 1958775623  928 LHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd05097    268 VFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
 637-961 5.08e-39

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 147.86  E-value: 5.08e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  637 KELDAKSVtleKSLGAGRFGDLCCGCLQLPGRQ-ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRg 715
Cdd:cd05108      5 KETEFKKI---KVLGSGAFGTVYKGLWIPEGEKvKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLT- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDR 795
Cdd:cd05108     81 STVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 A-EAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFG 874
Cdd:cd05108    161 AeEKEYH------------------------------------------------------AEGGKVPIKWMALESILHR 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05108    187 IYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFS 266


                   ....*..
gi 1958775623  955 KMGQEPE 961
Cdd:cd05108    267 KMARDPQ 273
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
 650-954 6.26e-39

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 146.08  E-value: 6.26e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQELPVAVHTLREgCSDSQKLS-FLAEALTLGQFDHSHIVRLEGVV--TRGNPLmIVTEYMN 726
Cdd:cd05058      3 IGKGHFGCVYHGTLIDSDGQKIHCAVKSLNR-ITDIEEVEqFLKEGIIMKDFSHPNVLSLLGIClpSEGSPL-VVLPYMK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDRAEAVYTTMVRS 806
Cdd:cd05058     81 HGDLRNFIRSETHNPTVKDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLA-RDIYDKEYYSVHNH 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 SllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd05058    160 T--------------------------------------------------GAKLPVKWMALESLQTQKFTTKSDVWSFG 189

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  887 IVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05058    190 VLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSELVSRIS 257
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
 627-956 1.48e-38

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 146.09  E-value: 1.48e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  627 DPLQAVHLFAKELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQE--LPVAVHTLREGCSDSQKLSFLAEALTLGQF-DHS 703
Cdd:cd05055     20 DPTQLPYDLKWEFPRNNLSFGKTLGAGAFGKVVEATAYGLSKSDavMKVAVKMLKPTAHSSEREALMSELKIMSHLgNHE 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  704 HIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHH-EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLI 782
Cdd:cd05055    100 NIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKrESFLTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKI 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  783 CKISGFGRGpRDraeavytTMVRSSllwphmllllsaiptgpmvYILAlppslpglfplvvpclsqpgsflrcgGSGRSP 862
Cdd:cd05055    180 VKICDFGLA-RD-------IMNDSN-------------------YVVK--------------------------GNARLP 206

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  863 ALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPG 941
Cdd:cd05055    207 VKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPvDSKFYKLIKEGYRMAQPEHAPAEIYDIMKTCWDADPL 286

                          330
                   ....*....|....*
gi 1958775623  942 ERPRFSQIHSILSKM 956
Cdd:cd05055    287 KRPTFKQIVQLIGKQ 301
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
 637-961 6.21e-38

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 143.63  E-value: 6.21e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  637 KELDAKSVtleKSLGAGRFGDLCCGCLQLPGRQ-ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05109      5 KETELKKV---KVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NpLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPR-D 794
Cdd:cd05109     82 T-VQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLlD 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFG 874
Cdd:cd05109    161 IDETEYH------------------------------------------------------ADGGKVPIKWMALESILHR 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05109    187 RFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVDEFS 266


                   ....*..
gi 1958775623  955 KMGQEPE 961
Cdd:cd05109    267 RMARDPS 273
SAM_EPH-A10 cd09549
SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 982-1051 8.50e-38

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188948  Cd Length: 70  Bit Score: 135.76  E-value: 8.50e-38
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  982 FSAFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09549      1 FSTFPSFGSVGEWLEALDLCRYKDNFAAAGYGSLEAVARMTAQDVLSLGITSLEHQELLLAGIQALRAQV 70
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
 644-956 1.01e-37

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 142.67  E-value: 1.01e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPL---- 718
Cdd:cd05035      1 LKLGKILGEGEFGSVMEAQLKQDDGSQLKVAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkpp 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 --MIVTEYMNLGALDDFLRHHEAE-----LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRg 791
Cdd:cd05035     81 spMVILPFMKHGDLHSYLLYSRLGglpekLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGL- 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  792 prdrAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpGSFLRCGGSGRSPALWAAPETL 871
Cdd:cd05035    160 ----SRKIYS------------------------------------------------GDYYRQGRISKMPVKWIALESL 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  872 QFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd05035    188 ADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVYFLMYFCWTVDPKDRPTFTKLRE 267


                   ....*
gi 1958775623  952 ILSKM 956
Cdd:cd05035    268 VLENI 272
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 650-956 1.66e-37

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 142.10  E-value: 1.66e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQeLPVAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVVTRGNPLMIVTEYMNLG 728
Cdd:cd05047      3 IGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPHG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  729 ALDDFLRHHE---------------AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRgpr 793
Cdd:cd05047     82 NLLDFLRKSRvletdpafaianstaSTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGL--- 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  794 DRAEAVYT--TMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsGRSPALWAAPETL 871
Cdd:cd05047    159 SRGQEVYVkkTM-------------------------------------------------------GRLPVRWMAIESL 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  872 QFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd05047    184 NYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILV 263


                   ....*
gi 1958775623  952 ILSKM 956
Cdd:cd05047    264 SLNRM 268
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
 648-956 1.90e-37

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 142.35  E-value: 1.90e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQlP---GRQELpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG--NPLMIVT 722
Cdd:cd05080     10 RDLGEGHFGKVSLYCYD-PtndGTGEM-VAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQggKSLQLIM 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELvtAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavytt 802
Cdd:cd05080     88 EYVPLGSLRDYLPKHSIGL--AQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFG------------- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllLLSAIPTGPMVYilalppslpglfplvvpclsqpgsflRCGGSGRSPALWAAPETLQFGHFSSASDV 882
Cdd:cd05080    153 -------------LAKAVPEGHEYY--------------------------RVREDGDSPVFWYAPECLKEYKFYYASDV 193

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  883 WSFGIVMWEVMAFGE------RPYWDM----SGQ----DVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQ 948
Cdd:cd05080    194 WSFGVTLYELLTHCDssqsppTKFLEMigiaQGQmtvvRLIELLERGERLPCPDKCPQEVYHLMKNCWETEASFRPTFEN 273


                   ....*...
gi 1958775623  949 IHSILSKM 956
Cdd:cd05080    274 LIPILKTV 281
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
 644-956 3.25e-37

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 141.30  E-value: 3.25e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCLQLPGrQELPVAVHTLREG-CSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG------- 715
Cdd:cd05075      2 LALGKTLGEGEFGSVMEGQLNQDD-SVLKVAVKTMKIAiCTRSEMEDFLSEAVCMKEFDHPNVMRLIGVCLQNtesegyp 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTeYMNLGALDDFLRHHE-----AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGR 790
Cdd:cd05075     81 SPVVILP-FMKHGDLHSFLLYSRlgdcpVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  791 gprdrAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpGSFLRCGGSGRSPALWAAPET 870
Cdd:cd05075    160 -----SKKIYN------------------------------------------------GDYYRQGRISKMPVKWIAIES 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  871 LQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIH 950
Cdd:cd05075    187 LADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLLNPKDRPSFETLR 266


                   ....*.
gi 1958775623  951 SILSKM 956
Cdd:cd05075    267 CELEKI 272
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
 637-961 4.17e-36

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 139.05  E-value: 4.17e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  637 KELDAKSVtleKSLGAGRFGDLCCGCLQLPGRQ-ELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRG 715
Cdd:cd05110      5 KETELKRV---KVLGSGAFGTVYKGIWVPEGETvKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NpLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPR-D 794
Cdd:cd05110     82 T-IQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLlE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcGGSGRSPALWAAPETLQFG 874
Cdd:cd05110    161 GDEKEYN------------------------------------------------------ADGGKMPIKWMALECIHYR 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  875 HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05110    187 KFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFS 266


                   ....*..
gi 1958775623  955 KMGQEPE 961
Cdd:cd05110    267 RMARDPQ 273
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
 628-956 7.75e-36

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 138.56  E-value: 7.75e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  628 PLQAVHLFAKEldakSVTLEKSLGAGRFGDL--CCGCLQLPGRQELP--VAVHTLREGCSDSQKLSFLAEALTLGQFD-H 702
Cdd:cd05099      2 PLDPKWEFPRD----RLVLGKPLGEGCFGQVvrAEAYGIDKSRPDQTvtVAVKMLKDNATDKDLADLISEMELMKLIGkH 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  703 SHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRH---------------HEAELVTAQLMGLLPGLASAMKYLSEMGYVH 767
Cdd:cd05099     78 KNIINLLGVCTQEGPLYVIVEYAAKGNLREFLRArrppgpdytfditkvPEEQLSFKDLVSCAYQVARGMEYLESRRCIH 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  768 RGLAARRVLLSSGLICKISGFG--RGPRDRAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpc 845
Cdd:cd05099    158 RDLAARNVLVTEDNVMKIADFGlaRGVHDIDYYKKTS------------------------------------------- 194

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  846 lsqpgsflrcggSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCP 925
Cdd:cd05099    195 ------------NGRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEELFKLLREGHRMDKPSNCT 262

                          330       340       350
                   ....*....|....*....|....*....|.
gi 1958775623  926 SQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05099    263 HELYMLMRECWHAVPTQRPTFKQLVEALDKV 293
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
 639-956 1.38e-34

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 133.91  E-value: 1.38e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVV----T 713
Cdd:cd14204      4 IDRNLLSLGKVLGEGEFGSVMEGELQQPDGTNHKVAVKTMKlDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVClevgS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  714 RGNPL-MIVTEYMNLGALDDFL---RHHEA-ELVTAQ-LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISG 787
Cdd:cd14204     84 QRIPKpMVILPFMKYGDLHSFLlrsRLGSGpQHVPLQtLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVAD 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  788 FGRgprdrAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpGSFLRCGGSGRSPALWAA 867
Cdd:cd14204    164 FGL-----SKKIYS------------------------------------------------GDYYRQGRIAKMPVKWIA 190

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  868 PETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFS 947
Cdd:cd14204    191 VESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLKQPEDCLDELYDIMYSCWRSDPTDRPTFT 270


                   ....*....
gi 1958775623  948 QIHSILSKM 956
Cdd:cd14204    271 QLRENLEKL 279
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
 639-949 3.27e-34

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 132.83  E-value: 3.27e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDL-CCGCLQLPGRQELPVAVHTLREGCSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRG-- 715
Cdd:cd14205      1 FEERHLKFLQQLGKGNFGSVeMCRYDPLQDNTGEVVAVKKLQHSTEEHLR-DFEREIEILKSLQHDNIVKYKGVCYSAgr 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdr 795
Cdd:cd14205     80 RNLRLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFG------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  796 aeavyttmvrssllwphmllllsaiptgpmvyilaLPPSLPglfplvvpclsQPGSFLRCGGSGRSPALWAAPETLQFGH 875
Cdd:cd14205    154 -----------------------------------LTKVLP-----------QDKEYYKVKEPGESPIFWYAPESLTESK 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  876 FSSASDVWSFGIVMWEVMAFGERP------YWDMSGQD---------VIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDP 940
Cdd:cd14205    188 FSVASDVWSFGVVLYELFTYIEKSksppaeFMRMIGNDkqgqmivfhLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNV 267


                   ....*....
gi 1958775623  941 GERPRFSQI 949
Cdd:cd14205    268 NQRPSFRDL 276
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
 645-953 7.86e-32

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 126.19  E-value: 7.86e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKL-SFLAEALTLGQFDHSHIVRLEGVVTRGNPL----- 718
Cdd:cd05074     12 TLGRMLGKGEFGSVREAQLKSEDGSFQKVAVKMLKADIFSSSDIeEFLREAACMKEFDHPNVIKLIGVSLRSRAKgrlpi 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  719 -MIVTEYMNLGALDDFL---RHHEAELVTAQ--LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRgp 792
Cdd:cd05074     92 pMVILPFMKHGDLHTFLlmsRIGEEPFTLPLqtLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGL-- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  793 rdrAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpGSFLRCGGSGRSPALWAAPETLQ 872
Cdd:cd05074    170 ---SKKIYS------------------------------------------------GDYYRQGCASKLPVKWLALESLA 198

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  873 FGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSI 952
Cdd:cd05074    199 DNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGNRLKQPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQ 278


                   .
gi 1958775623  953 L 953
Cdd:cd05074    279 L 279
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
 638-956 1.03e-31

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 126.67  E-value: 1.03e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDL----CCGCLQLPGRQELPVAVHTLREGCSDsQKLSFLAEALTLGQF--DHSHIVRLEGV 711
Cdd:cd05101     20 EFPRDKLTLGKPLGEGCFGQVvmaeAVGIDKDKPKEAVTVAVKMLKDDATE-KDLSDLVSEMEMMKMigKHKNIINLLGA 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  712 VTRGNPLMIVTEYMNLGALDDFLRHH---------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVL 776
Cdd:cd05101     99 CTQDGPLYVIVEYASKGNLREYLRARrppgmeysydinrvpEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVL 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  777 LSSGLICKISGFGRGpRDRAEAVYttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsfLRCG 856
Cdd:cd05101    179 VTENNVMKIADFGLA-RDINNIDY----------------------------------------------------YKKT 205

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  857 GSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECW 936
Cdd:cd05101    206 TNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCW 285

                          330       340
                   ....*....|....*....|
gi 1958775623  937 QKDPGERPRFSQIHSILSKM 956
Cdd:cd05101    286 HAVPSQRPTFKQLVEDLDRI 305
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
 646-954 1.38e-31

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 125.68  E-value: 1.38e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFG----------DLCCGCLQlpgrqelpVAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVVTR 714
Cdd:cd05054     11 LGKPLGRGAFGkviqasafgiDKSATCRT--------VAVKMLKEGATASEHKALMTELKILIHIgHHLNVVNLLGACTK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  715 -GNPLMIVTEYMNLGALDDFLR----------------HHEAE---------LVTAQLMGLLPGLASAMKYLSEMGYVHR 768
Cdd:cd05054     83 pGGPLMVIVEFCKFGNLSNYLRskreefvpyrdkgardVEEEEdddelykepLTLEDLICYSFQVARGMEFLASRKCIHR 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSGLICKISGFGRGpRDraeaVYTT--MVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpcl 846
Cdd:cd05054    163 DLAARNILLSENNVVKICDFGLA-RD----IYKDpdYVRK---------------------------------------- 197

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  847 sqpgsflrcgGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCP 925
Cdd:cd05054    198 ----------GDARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQmDEEFCRRLKEGTRMRAPEYTT 267

                          330       340
                   ....*....|....*....|....*....
gi 1958775623  926 SQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05054    268 PEIYQIMLDCWHGEPKERPTFSELVEKLG 296
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
 639-959 2.38e-31

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 125.11  E-value: 2.38e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  639 LDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQeLPVAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVVTRGNP 717
Cdd:cd05088      4 LEWNDIKFQDVIGEGNFGQVLKARIKKDGLR-MDAAIKRMKEYASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHE---------------AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLI 782
Cdd:cd05088     83 LYLAIEYAPHGNLLDFLRKSRvletdpafaianstaSTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYV 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  783 CKISGFGRgprDRAEAVYTTMVRssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggsGRSP 862
Cdd:cd05088    163 AKIADFGL---SRGQEVYVKKTM-----------------------------------------------------GRLP 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  863 ALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGE 942
Cdd:cd05088    187 VRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYE 266

                          330
                   ....*....|....*..
gi 1958775623  943 RPRFSQIHSILSKMGQE 959
Cdd:cd05088    267 RPSFAQILVSLNRMLEE 283
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
 638-949 5.99e-31

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 124.75  E-value: 5.99e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDL----CCGCLQLPGRQELPVAVHTLREGCSDsQKLSFLAEALTLGQF--DHSHIVRLEGV 711
Cdd:cd05100      8 ELSRTRLTLGKPLGEGCFGQVvmaeAIGIDKDKPNKPVTVAVKMLKDDATD-KDLSDLVSEMEMMKMigKHKNIINLLGA 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  712 VTRGNPLMIVTEYMNLGALDDFLRHH---------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVL 776
Cdd:cd05100     87 CTQDGPLYVLVEYASKGNLREYLRARrppgmdysfdtcklpEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVL 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  777 LSSGLICKISGFGRGpRDRAEAVYTTMVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcg 856
Cdd:cd05100    167 VTEDNVMKIADFGLA-RDVHNIDYYKKTTN-------------------------------------------------- 195

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  857 gsGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECW 936
Cdd:cd05100    196 --GRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECW 273

                          330
                   ....*....|...
gi 1958775623  937 QKDPGERPRFSQI 949
Cdd:cd05100    274 HAVPSQRPTFKQL 286
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
 650-949 1.90e-30

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 121.92  E-value: 1.90e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDL-CCGCLQLPGRQELPVAVHTLREGCSDSQKlSFLAEALTLGQFDHSHIVRLEGVV-TRGNP-LMIVTEYMN 726
Cdd:cd05081     12 LGKGNFGSVeLCRYDPLGDNTGALVAVKQLQHSGPDQQR-DFQREIQILKALHSDFIVKYRGVSyGPGRRsLRLVMEYLP 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrs 806
Cdd:cd05081     91 SGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFG----------------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  807 sllwphmllLLSAIPTGPMVYILALPpslpglfplvvpclsqpgsflrcggsGRSPALWAAPETLQFGHFSSASDVWSFG 886
Cdd:cd05081    154 ---------LAKLLPLDKDYYVVREP--------------------------GQSPIFWYAPESLSDNIFSRQSDVWSFG 198

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  887 IVMWEVMAFGERP------YWDMSGQD--------VIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05081    199 VVLYELFTYCDKScspsaeFLRMMGCErdvpalcrLLELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSAL 275
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
 648-949 4.41e-29

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 118.11  E-value: 4.41e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFG--DLCCGCLQLPGRQELpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTR--GNPLMIVTE 723
Cdd:cd05079     10 RDLGEGHFGkvELCRYDPEGDNTGEQ-VAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEdgGNGIKLIME 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttm 803
Cdd:cd05079     89 FLPSGSLKEYLPRNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFG-------------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  804 vrssllwphmllLLSAIPTGPMVYILAlppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPETLQFGHFSSASDVW 883
Cdd:cd05079    155 ------------LTKAIETDKEYYTVK--------------------------DDLDSPVFWYAPECLIQSKFYIASDVW 196

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  884 SFGIVMWEVMAFGERPYWDMS----------GQ----DVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05079    197 SFGVTLYELLTYCDSESSPMTlflkmigpthGQmtvtRLVRVLEEGKRLPRPPNCPEEVYQLMRKCWEFQPSKRTTFQNL 276
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
 635-949 5.21e-29

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 119.34  E-value: 5.21e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  635 FAKEldakSVTLEKSLGAGRFGDLccgcLQLP--GRQELP----VAVHTLREGCSDSQKLSFLAEALTLGQFDHS-HIVR 707
Cdd:cd14207      4 FARE----RLKLGKSLGRGAFGKV----VQASafGIKKSPtcrvVAVKMLKEGATASEYKALMTELKILIHIGHHlNVVN 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  708 LEGVVTR-GNPLMIVTEYMNLGALDDFLR---------------------HHEAELVTAQ-------------------- 745
Cdd:cd14207     76 LLGACTKsGGPLMVIVEYCKYGNLSNYLKskrdffvtnkdtslqeelikeKKEAEPTGGKkkrlesvtssesfassgfqe 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  746 --------------------------LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDraeav 799
Cdd:cd14207    156 dkslsdveeeeedsgdfykrpltmedLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLA-RD----- 229

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  800 yttmvrssllwphmllllsaIPTGPmvyilalppslpglfplvvpclsqpgSFLRcGGSGRSPALWAAPETLQFGHFSSA 879
Cdd:cd14207    230 --------------------IYKNP--------------------------DYVR-KGDARLPLKWMAPESIFDKIYSTK 262

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  880 SDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14207    263 SDVWSYGVLLWEIFSLGASPYPGVQiDEDFCSKLKEGIRMRAPEFATSEIYQIMLDCWQGDPNERPRFSEL 333
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 645-949 1.48e-28

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 115.70  E-value: 1.48e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   645 TLEKSLGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEY 724
Cdd:smart00220    2 EILEKLGEGSFGKVYLARDKKTGKL---VAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEY 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   725 MNLGALDDFLRHH------EAELVTAQLmgllpglASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraea 798
Cdd:smart00220   79 CEGGDLFDLLKKRgrlsedEARFYLRQI-------LSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFG--------- 142

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   799 vyttmvrssllwphmllllsaiptgpmvyiLAlppslpglfplvvpCLSQPGSFLR--CGgsgrSPAlWAAPETLQFGHF 876
Cdd:smart00220  143 ------------------------------LA--------------RQLDPGEKLTtfVG----TPE-YMAPEVLLGKGY 173

                           250       260       270       280       290       300       310
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623   877 SSASDVWSFGIVMWEvMAFGERPYWDMSGQDVI--KAVEDGFRLPPPR-NCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:smart00220  174 GKAVDIWSLGVILYE-LLTGKPPFPGDDQLLELfkKIGKPKPPFPPPEwDISPEAKDLIRKLLVKDPEKRLTAEEA 248
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
 638-949 2.19e-28

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 116.65  E-value: 2.19e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDL----CCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVV 712
Cdd:cd05098      9 ELPRDRLVLGKPLGEGCFGQVvlaeAIGLDKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIgKHKNIINLLGAC 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  713 TRGNPLMIVTEYMNLGALDDFLRHH---------------EAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLL 777
Cdd:cd05098     89 TQDGPLYVIVEYASKGNLREYLQARrppgmeycynpshnpEEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLV 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  778 SSGLICKISGFGRGpRDRAEAVYTTMVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgg 857
Cdd:cd05098    169 TEDNVMKIADFGLA-RDIHHIDYYKKTTN--------------------------------------------------- 196

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  858 sGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQ 937
Cdd:cd05098    197 -GRLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWH 275

                          330
                   ....*....|..
gi 1958775623  938 KDPGERPRFSQI 949
Cdd:cd05098    276 AVPSQRPTFKQL 287
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
 645-949 4.64e-27

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 111.42  E-value: 4.64e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGR---QELPVAVHTLREGCSDSQkLSFLAEALTLGQFDHSHIVRLEGVVTRGnPLMIV 721
Cdd:cd05037      2 TFHEHLGQGTFTNIYDGILREVGDgrvQEVEVLLKVLDSDHRDIS-ESFFETASLMSQISHKHLVKLYGVCVAD-ENIMV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  722 TEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLssgliCKISGFGrgprdraeavyt 801
Cdd:cd05037     80 QEYVRYGPLDKYLRRMGNNVPLSWKLQVAKQLASALHYLEDKKLIHGNVRGRNILL-----AREGLDG------------ 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 tmvrssllwphmllllsaipTGPMVYIlalppSLPGlFPLVVPCLSQPGSflrcggsgRSPalWAAPETLQFGH--FSSA 879
Cdd:cd05037    143 --------------------YPPFIKL-----SDPG-VPITVLSREERVD--------RIP--WIAPECLRNLQanLTIA 186

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  880 SDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPrNCPsQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05037    187 ADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAP-DCA-ELAELIMQCWTYEPTKRPSFRAI 254
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
 650-958 1.54e-26

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 109.83  E-value: 1.54e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCcgclqLPGRQELPVAVHTLRegcSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd14058      1 VGRGSFGVVC-----KARWRNQIVAVKIIE---SESEKKAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGS 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELV--TAQLMGLLPGLASAMKYLSEMG---YVHRGLAARRVLL-SSGLICKISGFGRgprdrAEAVYTTM 803
Cdd:cd14058     73 LYNVLHGKEPKPIytAAHAMSWALQCAKGVAYLHSMKpkaLIHRDLKPPNLLLtNGGTVLKICDFGT-----ACDISTHM 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  804 VRSSllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcgGSgrspALWAAPETLQFGHFSSASDVW 883
Cdd:cd14058    148 TNNK-------------------------------------------------GS----AAWMAPEVFEGSKYSEKCDVF 174

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  884 SFGIVMWEVMAfGERPYWDMSGQD--VIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKMGQ 958
Cdd:cd14058    175 SWGIILWEVIT-RRKPFDHIGGPAfrIMWAVHNGERPPLIKNCPKPIESLMTRCWSKDPEKRPSMKEIVKIMSHLMQ 250
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
 692-956 2.39e-26

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 108.89  E-value: 2.39e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  692 AEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAE-LVTAQLMGLLPGLASAMKYLSE---MGYVH 767
Cdd:cd14060     31 KEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYLNSNESEeMDMDQIMTWATDIAKGMHYLHMeapVKVIH 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  768 RGLAARRVLLSSGLICKISGFGrGPRDRAEAVYTTMVrssllwphmllllsaiptgpmvyilalppslpGLFPlvvpcls 847
Cdd:cd14060    111 RDLKSRNVVIAADGVLKICDFG-ASRFHSHTTHMSLV--------------------------------GTFP------- 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  848 qpgsflrcggsgrspalWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVI-KAVEDGFRLPPPRNCPS 926
Cdd:cd14060    151 -----------------WMAPEVIQSLPVSETCDTYSYGVVLWE-MLTREVPFKGLEGLQVAwLVVEKNERPTIPSSCPR 212

                          250       260       270
                   ....*....|....*....|....*....|
gi 1958775623  927 QLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14060    213 SFAELMRRCWEADVKERPSFKQIIGILESM 242
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
 673-959 4.01e-26

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 110.84  E-value: 4.01e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLREGCSDSQKLSFLAEALTLGQF-DHSHIVRLEGVVTRGN-PLMIVTEYMNLGALDDFLR--------------- 735
Cdd:cd05102     40 VAVKMLKEGATASEHKALMSELKILIHIgNHLNVVNLLGACTKPNgPLMVIVEFCKYGNLSNFLRakregfspyrerspr 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  736 ------------------HHEAELVTAQLMG---------------LLP-----------GLASAMKYLSEMGYVHRGLA 771
Cdd:cd05102    120 trsqvrsmveavradrrsRQGSDRVASFTEStsstnqprqevddlwQSPltmedlicysfQVARGMEFLASRKCIHRDLA 199

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  772 ARRVLLSSGLICKISGFGRGpRDraeavyttmvrssllwphmllllsaIPTGPmvyilalppslpglfplvvpclsqpgS 851
Cdd:cd05102    200 ARNILLSENNVVKICDFGLA-RD-------------------------IYKDP--------------------------D 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  852 FLRcGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHR 930
Cdd:cd05102    228 YVR-KGSARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQiNEEFCQRLKDGTRMRAPEYATPEIYR 306

                          330       340
                   ....*....|....*....|....*....
gi 1958775623  931 LMLECWQKDPGERPRFSQIHSILSKMGQE 959
Cdd:cd05102    307 IMLSCWHGDPKERPTFSDLVEILGDLLQE 335
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
 624-956 4.25e-26

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 111.48  E-value: 4.25e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  624 SCGDPLQAVHLFAKELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQE--LPVAVHTLREGCSDSQKLSFLAEALTLGQF- 700
Cdd:cd05106     20 TFIDPTQLPYNEKWEFPRDNLQFGKTLGAGAFGKVVEATAFGLGKEDnvLRVAVKMLKASAHTDEREALMSELKILSHLg 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  701 DHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHhEAELVTAQLM--------------------------------- 747
Cdd:cd05106    100 QHKNIVNLLGACTHGGPVLVITEYCCYGDLLNFLRK-KAETFLNFVMalpeisetssdyknitlekkyirsdsgfssqgs 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  748 --------------------------GLLP-----------GLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGR 790
Cdd:cd05106    179 dtyvemrpvsssssqssdskdeedteDSWPldlddllrfssQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGL 258

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  791 GpRDraeavytTMVRSSllwphmllllsaiptgpmvYILAlppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPET 870
Cdd:cd05106    259 A-RD-------IMNDSN-------------------YVVK--------------------------GNARLPVKWMAPES 285

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  871 LQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05106    286 IFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILvNSKFYKMVKRGYQMSRPDFAPPEIYSIMKMCWNLEPTERPTFSQI 365


                   ....*..
gi 1958775623  950 HSILSKM 956
Cdd:cd05106    366 SQLIQRQ 372
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
 627-949 2.72e-25

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 109.22  E-value: 2.72e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  627 DPLQAVHLFAKELDAKSVTLEKSLGAGRFGDL----CCGCLQLPGRqeLPVAVHTLREGCSDSQKLSFLAEALTLGQF-D 701
Cdd:cd05104     20 DPTQLPYDHKWEFPRDRLRFGKTLGAGAFGKVveatAYGLAKADSA--MTVAVKMLKPSAHSTEREALMSELKVLSYLgN 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  702 HSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLR-------------HHEAELV-------------TAQLMGLLPG--- 752
Cdd:cd05104     98 HINIVNLLGACTVGGPTLVITEYCCYGDLLNFLRrkrdsficpkfedLAEAALYrnllhqremacdsLNEYMDMKPSvsy 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  753 ---------------------------------------------LASAMKYLSEMGYVHRGLAARRVLLSSGLICKISG 787
Cdd:cd05104    178 vvptkadkrrgvrsgsyvdqdvtseileedelaldtedllsfsyqVAKGMEFLASKNCIHRDLAARNILLTHGRITKICD 257

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  788 FGRGPRDRAEAVYttmvrssllwphmllllsaiptgpmvyilalppslpglfplVVPclsqpgsflrcgGSGRSPALWAA 867
Cdd:cd05104    258 FGLARDIRNDSNY-----------------------------------------VVK------------GNARLPVKWMA 284

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  868 PETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd05104    285 PESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPvDSKFYKMIKEGYRMDSPEFAPSEMYDIMRSCWDADPLKRPTF 364


                   ...
gi 1958775623  947 SQI 949
Cdd:cd05104    365 KQI 367
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
 650-949 4.08e-25

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 104.27  E-value: 4.08e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd00180      1 LGKGSFGKVYKARDKETGKK---VAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGS 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrssll 809
Cdd:cd00180     78 LKDLLKENKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFG-------------------- 137

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvyiLAlppslpglfplvvpCLSQPGSFLRCGGSGRSPALWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd00180    138 -------------------LA--------------KDLDSDDSLLKTTGGTTPPYYAPPELLGGRYYGPKVDIWSLGVIL 184

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  890 WEVmafgerpywdmsgqdvikavedgfrlppprncpSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd00180    185 YEL---------------------------------EELKDLIRRMLQYDPKKRPSAKEL 211
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
 987-1047 2.65e-24

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 96.92  E-value: 2.65e-24
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  987 SFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09488      1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
 646-949 6.08e-24

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 104.68  E-value: 6.08e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFG----------DLCCGCLQlpgrqelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHS-HIVRLEGVVT- 713
Cdd:cd05103     11 LGKPLGRGAFGqvieadafgiDKTATCRT--------VAVKMLKEGATHSEHRALMSELKILIHIGHHlNVVNLLGACTk 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  714 RGNPLMIVTEYMNLGALDDFLRHHEAELV-------------------TAQLMGLLPGLASA------------------ 756
Cdd:cd05103     83 PGGPLMVIVEFCKFGNLSAYLRSKRSEFVpyktkgarfrqgkdyvgdiSVDLKRRLDSITSSqssassgfveekslsdve 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  757 -----------------------------MKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGpRDraeavyttmvrss 807
Cdd:cd05103    163 eeeagqedlykdfltledlicysfqvakgMEFLASRKCIHRDLAARNILLSENNVVKICDFGLA-RD------------- 228

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  808 llwphmllllsaiptgpmVYilalppslpglfplvvpclsQPGSFLRcGGSGRSPALWAAPETLQFGHFSSASDVWSFGI 887
Cdd:cd05103    229 ------------------IY--------------------KDPDYVR-KGDARLPLKWMAPETIFDRVYTIQSDVWSFGV 269

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  888 VMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05103    270 LLWEIFSLGASPYPGVKiDEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSEL 332
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
 650-949 1.01e-23

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 101.03  E-value: 1.01e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLqlpgRQElPVAVHTLREgcsdsQKLSflaEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd14059      1 LGSGAQGAVFLGKF----RGE-EVAVKKVRD-----EKET---DIKHLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQ 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHhEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG--RGPRDRAeavyTTMvrss 807
Cdd:cd14059     68 LYEVLRA-GREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGtsKELSEKS----TKM---- 138

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  808 llwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgSFlrcGGSgrspALWAAPETLQFGHFSSASDVWSFGI 887
Cdd:cd14059    139 -------------------------------------------SF---AGT----VAWMAPEVIRNEPCSEKVDIWSFGV 168

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  888 VMWEVMAfGERPYWDMSGQDVIKAV-EDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14059    169 VLWELLT-GEIPYKDVDSSAIIWGVgSNSLQLPVPSTCPDGFKLLMKQCWNSKPRNRPSFRQI 230
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
 627-956 4.08e-23

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 103.17  E-value: 4.08e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  627 DPLQAVHLFAKELDAKSVTLEKSLGAGRFGDLCCGCLQ-LPGRQE-LPVAVHTLREGCSDSQKLSFLAEALTLGQFD-HS 703
Cdd:cd05107     22 DPMQLPYDSAWEMPRDNLVLGRTLGSGAFGRVVEATAHgLSHSQStMKVAVKMLKSTARSSEKQALMSELKIMSHLGpHL 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  704 HIVRLEGVVTRGNPLMIVTEYMNLGALDD--------FLRHH------EAELVTAQLMGLLP------------------ 751
Cdd:cd05107    102 NIVNLLGACTKGGPIYIITEYCRYGDLVDylhrnkhtFLQYYldknrdDGSLISGGSTPLSQrkshvslgsesdggymdm 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  752 -----------------------------------------------------------------GLASAMKYLSEMGYV 766
Cdd:cd05107    182 skdesadyvpmqdmkgtvkyadiessnyespydqylpsapertrrdtlinespalsymdlvgfsyQVANGMEFLASKNCV 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  767 HRGLAARRVLLSSGLICKISGFGRGpRDraeavyttMVRSSLlwphmllllsaiptgpmvYIlalppslpglfplvvpcl 846
Cdd:cd05107    262 HRDLAARNVLICEGKLVKICDFGLA-RD--------IMRDSN------------------YI------------------ 296

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  847 SQPGSFLrcggsgrsPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDMS-GQDVIKAVEDGFRLPPPRNCP 925
Cdd:cd05107    297 SKGSTFL--------PLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYPELPmNEQFYNAIKRGYRMAKPAHAS 368

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1958775623  926 SQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05107    369 DEIYEIMQKCWEEKFEIRPDFSQLVHLVGDL 399
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
 645-945 6.22e-23

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 99.58  E-value: 6.22e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRqelPVAVHTLREGCSDSQKLS--FLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:cd14014      3 RLVRLLGRGGMGEVYRARDTLLGR---PVAIKVLRPELAEDEEFRerFLREARALARLSHPNIVRVYDVGEDDGRPYIVM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHeAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavytt 802
Cdd:cd14014     80 EYVEGGSLADLLRER-GPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFG------------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllllsaiptgpmvyiLALPPSLPGlfplvvpcLSQPGSFLrcGgsgrSPAlWAAPETLQFGHFSSASDV 882
Cdd:cd14014    146 --------------------------IARALGDSG--------LTQTGSVL--G----TPA-YMAPEQARGGPVDPRSDI 184

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  883 WSFGIVMWEvMAFGERPYwDMSGQDVIKAVEDGFRLPPPR----NCPSQLHRLMLECWQKDPGERPR 945
Cdd:cd14014    185 YSLGVVLYE-LLTGRPPF-DGDSPAAVLAKHLQEAPPPPSplnpDVPPALDAIILRALAKDPEERPQ 249
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
 673-956 1.17e-22

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 98.62  E-value: 1.17e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLR-EGCSDSQKL--SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDdflRHHEAELVT-AQLMG 748
Cdd:cd14061     20 VAVKAARqDPDEDISVTleNVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALN---RVLAGRKIPpHVLVD 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  749 LLPGLASAMKYL---SEMGYVHRGLAARRVLLSSGL--------ICKISGFGRGprdrAEAVYTTMVrssllwphmllll 817
Cdd:cd14061     97 WAIQIARGMNYLhneAPVPIIHRDLKSSNILILEAIenedlenkTLKITDFGLA----REWHKTTRM------------- 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  818 saiptgpmvyilalppslpglfplvvpclSQPGSFLrcggsgrspalWAAPETLQFGHFSSASDVWSFGIVMWEVMAfGE 897
Cdd:cd14061    160 -----------------------------SAAGTYA-----------WMAPEVIKSSTFSKASDVWSYGVLLWELLT-GE 198

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  898 RPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14061    199 VPYKGIDGLAVAYGVAvNKLTLPIPSTCPEPFAQLMKDCWQPDPHDRPSFADILKQLENI 258
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
 627-956 4.14e-22

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 100.10  E-value: 4.14e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  627 DPLQAVHLFAKELDAKSVTLEKSLGAGRFGDLCCGCLQLPGRQE--LPVAVHTLREGCSDSQKLSFLAEALTLGQFD-HS 703
Cdd:cd05105     22 DPMQLPYDSRWEFPRDGLVLGRILGSGAFGKVVEGTAYGLSRSQpvMKVAVKMLKPTARSSEKQALMSELKIMTHLGpHL 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  704 HIVRLEGVVTRGNPLMIVTEYMNLGAL--------DDFL-RHHEAELVTAQLMGLLPG---------------------- 752
Cdd:cd05105    102 NIVNLLGACTKSGPIYIITEYCFYGDLvnylhknrDNFLsRHPEKPKKDLDIFGINPAdestrsyvilsfenkgdymdmk 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  753 ----------------------------------------------------------------LASAMKYLSEMGYVHR 768
Cdd:cd05105    182 qadttqyvpmleikeaskysdiqrsnydrpasykgsndsevknllsddgseglttldllsftyqVARGMEFLASKNCVHR 261

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSGLICKISGFGRGPRDRAEAVYttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQ 848
Cdd:cd05105    262 DLAARNVLLAQGKIVKICDFGLARDIMHDSNY---------------------------------------------VSK 296

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 PGSFLrcggsgrsPALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWDM-SGQDVIKAVEDGFRLPPPRNCPSQ 927
Cdd:cd05105    297 GSTFL--------PVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMiVDSTFYNKIKSGYRMAKPDHATQE 368

                          410       420
                   ....*....|....*....|....*....
gi 1958775623  928 LHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd05105    369 VYDIMVKCWNSEPEKRPSFLHLSDIVESL 397
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
 650-949 1.03e-21

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 96.26  E-value: 1.03e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQlpGRQelpVAVHTLREGCSDSQKL---SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMN 726
Cdd:cd14146      2 IGVGGFGKVYRATWK--GQE---VAVKAARQDPDEDIKAtaeSVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFAR 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFLRHHEAELVTAQLMGLLP--------GLASAMKYLSEMGYV---HRGLAARRVLLSSGL----IC----KISG 787
Cdd:cd14146     77 GGTLNRALAAANAAPGPRRARRIPPhilvnwavQIARGMLYLHEEAVVpilHRDLKSSNILLLEKIehddICnktlKITD 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  788 FGRGprdrAEAVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLrcggsgrspalWAA 867
Cdd:cd14146    157 FGLA----REWHRTTK------------------------------------------MSAAGTYA-----------WMA 179

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  868 PETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd14146    180 PEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAvNKLTLPIPSTCPEPFAKLMKECWEQDPHIRPSF 258


                   ...
gi 1958775623  947 SQI 949
Cdd:cd14146    259 ALI 261
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
 644-944 4.28e-21

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 93.81  E-value: 4.28e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGcLQLPGRQElpVAVHTLR-EGCSDSQKLsfLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:cd05122      2 FEILEKIGKGGFGVVYKA-RHKKTGQI--VAIKKINlESKEKKESI--LNEIAILKKCKHPNIVKYYGSYLKKDELWIVM 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSS-GLIcKISGFGrgprdraeavyt 801
Cdd:cd05122     77 EFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSdGEV-KLIDFG------------ 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 tmvrssllwphmllllsaiptgpmvyilalppslpglfpLVVPCLSQPGSFLRCGgsgrSPAlWAAPETLQFGHFSSASD 881
Cdd:cd05122    144 ---------------------------------------LSAQLSDGKTRNTFVG----TPY-WMAPEVIQGKPYGFKAD 179

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  882 VWSFGIVMWEvMAFGERPYWDMSGQDVIK--AVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd05122    180 IWSLGITAIE-MAEGKPPYSELPPMKALFliATNGPPGLRNPKKWSKEFKDFLKKCLQKDPEKRP 243
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
 648-954 3.33e-20

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 91.94  E-value: 3.33e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCG---CLQLPGRqelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEY 724
Cdd:cd14206      3 QEIGNGWFGKVILGeifSDYTPAQ----VVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  725 MNLGALDDFLRHHEA-----------ELVTAQLMGLlpGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPR 793
Cdd:cd14206     79 CQLGDLKRYLRAQRKadgmtpdlptrDLRTLQRMAY--EITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHN 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  794 DRAEAVYTTMVRssllwphmllllsaiptgpmvyilalppslpglfpLVVPclsqpgsfLRcggsgrspalWAAPETLQF 873
Cdd:cd14206    157 NYKEDYYLTPDR-----------------------------------LWIP--------LR----------WVAPELLDE 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  874 GHF-------SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAV--EDGFRLPPPR-NCP--SQLHRLMLECWqKDPG 941
Cdd:cd14206    184 LHGnlivvdqSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVvrEQQMKLAKPRlKLPyaDYWYEIMQSCW-LPPS 262

                          330
                   ....*....|...
gi 1958775623  942 ERPRFSQIHSILS 954
Cdd:cd14206    263 QRPSVEELHLQLS 275
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
 638-949 6.60e-20

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 90.87  E-value: 6.60e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLCcgcLQLPGRQElpVAVHTLREGCSD--SQKL-SFLAEALTLGQFDHSHIVRLEGVVTR 714
Cdd:cd14145      2 EIDFSELVLEEIIGIGGFGKVY---RAIWIGDE--VAVKAARHDPDEdiSQTIeNVRQEAKLFAMLKHPNIIALRGVCLK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  715 GNPLMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYLSEMGYV---HRGLAARRVLLS--------SGLIC 783
Cdd:cd14145     77 EPNLCLVMEFARGGPLNRVLSGKR--IPPDILVNWAVQIARGMNYLHCEAIVpviHRDLKSSNILILekvengdlSNKIL 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  784 KISGFGRGprdrAEAVYTTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLrcggsgrspa 863
Cdd:cd14145    155 KITDFGLA----REWHRTTK------------------------------------------MSAAGTYA---------- 178

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  864 lWAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGE 942
Cdd:cd14145    179 -WMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAmNKLSLPIPSTCPEPFARLMEDCWNPDPHS 256


                   ....*..
gi 1958775623  943 RPRFSQI 949
Cdd:cd14145    257 RPPFTNI 263
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
 650-953 6.70e-20

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 90.53  E-value: 6.70e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLccgclqLPGRQELPVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNpLMIVTEYMNLG 728
Cdd:cd14062      1 IGSGSFGTV------YKGRWHGDVAVKKLNvTDPTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQ-LAIVTQWCEGS 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  729 ALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeaVYTTMVRSSL 808
Cdd:cd14062     74 SLYKHLHVLETKFEMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFG---------LATVKTRWSG 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  809 LwphmllllsaiptgpmvyilalppslpglfplvvPCLSQP-GSFLrcggsgrspalWAAPETLQF---GHFSSASDVWS 884
Cdd:cd14062    145 S----------------------------------QQFEQPtGSIL-----------WMAPEVIRMqdeNPYSFQSDVYA 179

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  885 FGIVMWEVMAfGERPYWDMSGQD-VIKAVEDGFrLPPPR-----NCPSQLHRLMLECWQKDPGERPRFSQIHSIL 953
Cdd:cd14062    180 FGIVLYELLT-GQLPYSHINNRDqILFMVGRGY-LRPDLskvrsDTPKALRRLMEDCIKFQRDERPLFPQILASL 252
EphA2_TM pfam14575
Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer ...
 569-641 6.75e-20

Ephrin type-A receptor 2 transmembrane domain; Epha2_TM represents the left-handed dimer transmembrane domain of of EphA2 receptor. This domain oligomerises and is important for the active signalling process.


Pssm-ID: 464211  Cd Length: 72  Bit Score: 84.58  E-value: 6.75e-20
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  569 TVVTISALLVLGSVMSVLAIWRRPCDGKGSGnAHDEEELYFHFKVPTRRTFLDPQSCGDPLQAVHLFAKELDA 641
Cdd:pfam14575    1 VVASVAGGLVLLLVVGVVLIRRRRCCGRKKS-QDDDEEEFHQYKPPGRKTYIDPHTYEDPNQAVLEFAKEIDA 72
SAM_EPH-A4 cd09545
SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 986-1056 6.79e-20

SAM domain of EPH-A4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A4 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of EPH-A4 receptors can form homodimers. EPH-A4 receptors bind ligands such as erphirin A1, A4, A5. They are known to interact with a number of different proteins, including meltrin beta metalloprotease, Cdk5, and EFS2alpha, however SAM domain doesn't participate in these interactions. EPH-A4 receptors are involved in regulation of corticospinal tract formation, in pathway controlling voluntary movements, in formation of motor neurons, and in axon guidance (SAM domain is not required for axon guidance or for EPH-A4 kinase signaling). In Xenopus embryos EPH-A4 induces loss of cell adhesion, ventro-lateral protrusions, and severely expanded posterior structures. Mutations in SAM domain conserved tyrosine (Y928F) enhance the ability of EPH-A4 to induce these phenotypes, thus supporting the idea that the SAM domain may negatively regulate some aspects of EPH-A4 activity. EphA4 gene was found overexpressed in a number of different cancers including human gastric cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. It is likely to be a promising molecular target for the cancer therapy.


Pssm-ID: 188944  Cd Length: 71  Bit Score: 84.62  E-value: 6.79e-20
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  986 PSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRVLQLQG 1056
Cdd:cd09545      1 SAVASVDDWLQAIKMERYKDNFTAAGYTTLEAVVHMNQDDLARIGISAIAHQNKILSSVQGMRSQMQQMQG 71
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
 638-951 1.12e-19

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 90.48  E-value: 1.12e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLccgclqLPGRQELPVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGN 716
Cdd:cd14149      8 EIEASEVMLSTRIGSGSFGTV------YKGKWHGDVAVKILKvVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  717 pLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdra 796
Cdd:cd14149     82 -LAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFG------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 eaVYTTMVRSSLLWPHMLlllsaiPTGPMvyilalppslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQF--- 873
Cdd:cd14149    154 --LATVKSRWSGSQQVEQ------PTGSI--------------------------------------LWMAPEVIRMqdn 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  874 GHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQD-VIKAVEDGFRLPPP----RNCPSQLHRLMLECWQKDPGERPRFSQ 948
Cdd:cd14149    188 NPFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqIIFMVGRGYASPDLsklyKNCPKAMKRLVADCIKKVKEERPLFPQ 266


                   ...
gi 1958775623  949 IHS 951
Cdd:cd14149    267 ILS 269
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
 645-944 1.29e-19

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 89.59  E-value: 1.29e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRQelpVAVHTL-REGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd06627      3 QLGDLIGRGAFGSVYKGLNLNTGEF---VAIKQIsLEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRHHEA---ELVTAQLMGLLPGLAsamkYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeaVY 800
Cdd:cd06627     80 YVENGSLASIIKKFGKfpeSLVAVYIYQVLEGLA----YLHEQGVIHRDIKGANILTTKDGLVKLADFG---------VA 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  801 TTMVRSSLLwphmllllsaiptgpmvyilalPPSLPGlfplvvpclsqpgsflrcggsgrSPaLWAAPETLQFGHFSSAS 880
Cdd:cd06627    147 TKLNEVEKD----------------------ENSVVG-----------------------TP-YWMAPEVIEMSGVTTAS 180

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  881 DVWSFGIVMWEVMAfGERPYWDMSG-QDVIKAVEDgfRLPP-PRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd06627    181 DIWSVGCTVIELLT-GNPPYYDLQPmAALFRIVQD--DHPPlPENISPELRDFLLQCFQKDPTLRP 243
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
 865-949 1.06e-18

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 86.96  E-value: 1.06e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd14148    167 WMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAmNKLTLPIPSTCPEPFARLLEECWDPDPHGR 245


                   ....*.
gi 1958775623  944 PRFSQI 949
Cdd:cd14148    246 PDFGSI 251
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
 648-954 2.92e-18

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 86.10  E-value: 2.92e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLqLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd05042      1 QEIGNGWFGKVLLGEI-YSGTSVAQVVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRH---HE---AELVTAQLMGLlpGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAEAVYT 801
Cdd:cd05042     80 GDLKAYLRSereHErgdSDTRTLQRMAC--EVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKEDYIE 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 TMVRssllwphmllllsaiptgpmvyilalppslpglfpLVVPclsqpgsfLRcggsgrspalWAAPETLQFGHF----- 876
Cdd:cd05042    158 TDDK-----------------------------------LWFP--------LR----------WTAPELVTEFHDrllvv 184

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  877 --SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAV--EDGFRLPPPR---NCPSQLHRLMLECWQKdPGERPRFSQI 949
Cdd:cd05042    185 dqTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQlelPYSDRWYEVLQFCWLS-PEQRPAAEDV 263


                   ....*
gi 1958775623  950 HSILS 954
Cdd:cd05042    264 HLLLT 268
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
 650-956 3.39e-18

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 85.79  E-value: 3.39e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLqlpgRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd14066      1 IGSGGFGTVYKGVL----ENGTVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGS 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAE--LVTAQLMGLLPGLASAMKYLSEMGY---VHRGLAARRVLLSSGLICKISGFG--RGPRDRAEAVYTT 802
Cdd:cd14066     77 LEDRLHCHKGSppLPWPQRLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLTDFGlaRLIPPSESVSKTS 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSSllwphmllllsaiptgpMVYIlalppslpglfplvvpclsqpgsflrcggsgrspalwaAPETLQFGHFSSASDV 882
Cdd:cd14066    157 AVKGT-----------------IGYL--------------------------------------APEYIRTGRVSTKSDV 181

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  883 WSFGIVMWEVMAfGERPY----WDMSGQDVIKAVEDGF----------RLPPPRNCPS----QLHRLMLECWQKDPGERP 944
Cdd:cd14066    182 YSFGVVLLELLT-GKPAVdenrENASRKDLVEWVESKGkeeledildkRLVDDDGVEEeeveALLRLALLCTRSDPSLRP 260

                          330
                   ....*....|..
gi 1958775623  945 RFSQIHSILSKM 956
Cdd:cd14066    261 SMKEVVQMLEKL 272
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
 644-949 6.51e-18

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 85.07  E-value: 6.51e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLccgclqLPGRQELPVAVHTLREGCSDSQKL-SFLAEALTLGQFDHSHIVRLEGVVTRGNpLMIVT 722
Cdd:cd14150      2 VSMLKRIGTGSFGTV------FRGKWHGDVAVKILKVTEPTPEQLqAFKNEMQVLRKTRHVNILLFMGFMTRPN-FAIIT 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeaVYTT 802
Cdd:cd14150     75 QWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFG---------LATV 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSSLLWPhmllllsaiptgpmvyilalppslpglfplvvpcLSQPGsflrcgGSgrspALWAAPETLQF---GHFSSA 879
Cdd:cd14150    146 KTRWSGSQQ----------------------------------VEQPS------GS----ILWMAPEVIRMqdtNPYSFQ 181

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  880 SDVWSFGIVMWEVMAfGERPYWDMSGQD-VIKAVEDGFRLPP----PRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14150    182 SDVYAYGVVLYELMS-GTLPYSNINNRDqIIFMVGRGYLSPDlsklSSNCPKAMKRLLIDCLKFKREERPLFPQI 255
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
 865-956 1.09e-17

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 84.31  E-value: 1.09e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVE-DGFRLPPPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd14147    176 WMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAvNKLTLPIPSTCPEPFAQLMADCWAQDPHRR 254

                           90
                   ....*....|...
gi 1958775623  944 PRFSQIHSILSKM 956
Cdd:cd14147    255 PDFASILQQLEAL 267
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
 650-949 1.65e-17

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 83.31  E-value: 1.65e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLccgcLQLPGRQELPVAVhtLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd14065      1 LGKGFFGEV----YKVTHRETGKVMV--MKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGT 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLssglicKISGFGRgprdraEAVYTTmvrssll 809
Cdd:cd14065     75 LEELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLV------REANRGR------NAVVAD------- 135

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvYILA-LPPSLPGLFPLVVPCLSQPGSflrcggsgrspALWAAPETLQFGHFSSASDVWSFGIV 888
Cdd:cd14065    136 -----------------FGLArEMPDEKTKKPDRKKRLTVVGS-----------PYWMAPEMLRGESYDEKVDVFSFGIV 187

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  889 MWEVMAF-----GERPYWDMSGQDVikaveDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14065    188 LCEIIGRvpadpDYLPRTMDFGLDV-----RAFRTLYVPDCPPSFLPLAIRCCQLDPEKRPSFVEL 248
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
 673-946 1.67e-17

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 83.66  E-value: 1.67e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLREGCSDS-QKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrHHEAELVTAQLMG-LL 750
Cdd:cd13978     21 VAIKCLHSSPNCIeERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLKSLL-EREIQDVPWSLRFrII 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  751 PGLASAMKYLSEM--GYVHRGLAARRVLLSSGLICKISGFGRgprdraeAVYTTMVRSSLLWPHMllllsaiptgpmvyi 828
Cdd:cd13978    100 HEIALGMNFLHNMdpPLLHHDLKPENILLDNHFHVKISDFGL-------SKLGMKSISANRRRGT--------------- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  829 lalppslpglfplvvpclsqpgsflrcGGSGRSPAlWAAPETLQFGH--FSSASDVWSFGIVMWEVMAfGERPYWDMSGQ 906
Cdd:cd13978    158 ---------------------------ENLGGTPI-YMAPEAFDDFNkkPTSKSDVYSFAIVIWAVLT-RKEPFENAINP 208

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1958775623  907 DVIKA---------VEDGFRLPPPRNCPsQLHRLMLECWQKDPGERPRF 946
Cdd:cd13978    209 LLIMQivskgdrpsLDDIGRLKQIENVQ-ELISLMIRCWDGNPDARPTF 256
Pkinase pfam00069
Protein kinase domain;
645-949 2.02e-17

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 82.29  E-value: 2.02e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGdLCCGCLQLPGRQElpVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:pfam00069    2 EVLRKLGSGSFG-TVYKAKHRDTGKI--VAIKKIKkEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRHHeaelvtaqlmgllpglasamKYLSEMgyvHRGLAARRVLlssglickisgfgrgprdraEAVYTTM 803
Cdd:pfam00069   79 YVEGGSLFDLLSEK--------------------GAFSER---EAKFIMKQIL--------------------EGLESGS 115

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  804 VRSSllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflRCGGSGrspalWAAPETLQFGHFSSASDVW 883
Cdd:pfam00069  116 SLTT----------------------------------------------FVGTPW-----YMAPEVLGGNPYGPKVDVW 144

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  884 SFGIVMWEvMAFGERPYWDMSGQDVIKAV--EDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:pfam00069  145 SLGCILYE-LLTGKPPFPGINGNEIYELIidQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRLTATQA 211
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
 638-959 2.98e-17

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 83.19  E-value: 2.98e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  638 ELDAKSVTLEKSLGAGRFGDLccgclqLPGRQELPVAVHTLREGCSDSQKL-SFLAEALTLGQFDHSHIVRLEGVVTRGN 716
Cdd:cd14151      4 EIPDGQITVGQRIGSGSFGTV------YKGKWHGDVAVKMLNVTAPTPQQLqAFKNEVGVLRKTRHVNILLFMGYSTKPQ 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  717 pLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdra 796
Cdd:cd14151     78 -LAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFG------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  797 eavyTTMVRSSllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLRCGGSgrspALWAAPETLQF--- 873
Cdd:cd14151    150 ----LATVKSR--------------------------------------WSGSHQFEQLSGS----ILWMAPEVIRMqdk 183

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  874 GHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQD-VIKAVEDGFRLPP----PRNCPSQLHRLMLECWQKDPGERPRFSQ 948
Cdd:cd14151    184 NPYSFQSDVYAFGIVLYELMT-GQLPYSNINNRDqIIFMVGRGYLSPDlskvRSNCPKAMKRLMAECLKKKRDERPLFPQ 262

                          330
                   ....*....|.
gi 1958775623  949 IHSILSKMGQE 959
Cdd:cd14151    263 ILASIELLARS 273
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
 669-949 3.16e-17

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 83.06  E-value: 3.16e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  669 QELPVAVHTLREGCSDSQkLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMG 748
Cdd:cd05077     35 KEIKVILKVLDPSHRDIS-LAFFETASMMRQVSHKHIVLLYGVCVRDVENIMVEEFVEFGPLDLFMHRKSDVLTTPWKFK 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  749 LLPGLASAMKYLSEMGYVHRGLAARRVLLSsglickisgfgrgpRDRAEAVYttmvrssllwphmllllsaiptGPMVYI 828
Cdd:cd05077    114 VAKQLASALSYLEDKDLVHGNVCTKNILLA--------------REGIDGEC----------------------GPFIKL 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  829 lalppSLPGLfPLVVpcLSqpgsflRCGGSGRSPalWAAPETLQ-FGHFSSASDVWSFGIVMWEVMAFGERPYWDMSGQD 907
Cdd:cd05077    158 -----SDPGI-PITV--LS------RQECVERIP--WIAPECVEdSKNLSIAADKWSFGTTLWEICYNGEIPLKDKTLAE 221

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1958775623  908 VIKAVEDGFRLPPPrNCpSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05077    222 KERFYEGQCMLVTP-SC-KELADLMTHCMNYDPNQRPFFRAI 261
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
645-944 3.93e-17

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 85.83  E-value: 3.93e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRqelPVAVHTLREGCSDSQKL--SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:COG0515     10 RILRLLGRGGMGVVYLARDLRLGR---PVALKVLRPELAADPEAreRFRREARALARLNHPNIVRVYDVGEEDGRPYLVM 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAeLVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavytt 802
Cdd:COG0515     87 EYVEGESLADLLRRRGP-LPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFG------------- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 mvrssllwphmllllsaiptgpmvyiLALPPSLPGlfplvvpcLSQPGSFLrcgGSgrspALWAAPETLQFGHFSSASDV 882
Cdd:COG0515    153 --------------------------IARALGGAT--------LTQTGTVV---GT----PGYMAPEQARGEPVDPRSDV 191

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  883 WSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGFRLPPPR---NCPSQLHRLMLECWQKDPGERP 944
Cdd:COG0515    192 YSLGVTLYE-LLTGRPPFDGDSPAELLRAHLREPPPPPSElrpDLPPALDAIVLRALAKDPEERY 255
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
 650-944 5.31e-17

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 82.18  E-value: 5.31e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFL-AEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLG 728
Cdd:cd06606      8 LGKGSFGSVYLALNLDTGEL---MAVKEVELSGDSEEELEALeREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  729 ALDDFLRH----HEAE--LVTAQLmglLPGLAsamkYLSEMGYVHRGLAARRVLLSSGLICKISGFGrGPRDRAEAVYTT 802
Cdd:cd06606     85 SLASLLKKfgklPEPVvrKYTRQI---LEGLE----YLHSNGIVHRDIKGANILVDSDGVVKLADFG-CAKRLAEIATGE 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflRCGgsgrSPaLWAAPETLQFGHFSSASDV 882
Cdd:cd06606    157 GTKS-----------------------------------------------LRG----TP-YWMAPEVIRGEGYGRAADI 184

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  883 WSFGIVMWEvMAFGERPYWDMSGQ-DVIKAVEDGFRLPP-PRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd06606    185 WSLGCTVIE-MATGKPPWSELGNPvAALFKIGSSGEPPPiPEHLSEEAKDFLRKCLQRDPKKRP 247
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
 648-954 5.95e-17

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 82.34  E-value: 5.95e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQlPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd05087      3 KEIGHGWFGKVFLGEVN-SGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCPL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRH-HEAELVTAQ---LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAEAVYTTM 803
Cdd:cd05087     82 GDLKGYLRScRAAESMAPDpltLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVTA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  804 VRssllwphmllllsaiptgpmvyilalppslpglfpLVVPclsqpgsfLRcggsgrspalWAAPETLQFGHF------- 876
Cdd:cd05087    162 DQ-----------------------------------LWVP--------LR----------WIAPELVDEVHGnllvvdq 188

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  877 SSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAV--EDGFRLPPPR---NCPSQLHRLMLECWQKdPGERPRFSQIHS 951
Cdd:cd05087    189 TKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTvrEQQLKLPKPQlklSLAERWYEVMQFCWLQ-PEQRPTAEEVHL 267


                   ...
gi 1958775623  952 ILS 954
Cdd:cd05087    268 LLS 270
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
 697-943 1.78e-16

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 80.34  E-value: 1.78e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHE--AELVTAQLMGllpGLASAMKYLSEMGYVHRGLAARR 774
Cdd:cd14009     46 LKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQYIRKRGrlPEAVARHFMQ---QLASGLKFLRSKNIIHRDLKPQN 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  775 VLLSS---GLICKISGFGrgprdraeavyttMVRSsllwphmllllsaIPTGPMVYILalppslpglfplvvpclsqpgs 851
Cdd:cd14009    123 LLLSTsgdDPVLKIADFG-------------FARS-------------LQPASMAETL---------------------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  852 flrCGgsgrSPaLWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYwdmSGQDV------IKAVEDGFRLPPPRN-- 923
Cdd:cd14009    155 ---CG----SP-LYMAPEILQFQKYDAKADLWSVGAILFE-MLVGKPPF---RGSNHvqllrnIERSDAVIPFPIAAQls 222

                          250       260
                   ....*....|....*....|..
gi 1958775623  924 --CPSQLHRLMlecwQKDPGER 943
Cdd:cd14009    223 pdCKDLLRRLL----RRDPAER 240
SAM_EPH-A7 cd09548
SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 985-1051 2.25e-16

SAM domain of EPH-A7 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A7 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A7 receptors and appears to mediate cell-cell initiated signal transduction. EphA7 was found expressed in human embryonic stem (ES) cells, neural tissues, kidney vasculature. EphA7 knockout mice show decrease in cortical progenitor cell death at mid-neurogenesis and significant increase in cortical size. EphA7 may be involved in the pathogenesis and development of different cancers; in particular, EphA7 was found upregulated in glioblastoma and downregulated in colorectal cancer and gastric cancer. Thus, it is a potential molecular marker and/or therapy target for these types of cancers.


Pssm-ID: 188947  Cd Length: 70  Bit Score: 74.68  E-value: 2.25e-16
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09548      4 FTSFCSVGEWLEAIKMERYKDNFTAAGYNSLESVARMTIEDVMSLGITLVGHQKKIMSSIQTMRAQM 70
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
 644-949 4.84e-16

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 79.18  E-value: 4.84e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGCLQLPGRQE---LPVAVHTLREGCSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMi 720
Cdd:cd14208      1 LTFMESLGKGSFTKIYRGLRTDEEDDErceTEVLLKVMDPTHGNCQE-SFLEAASIMSQISHKHLVLLHGVCVGKDSIM- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  721 VTEYMNLGALDDFLR--HHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLS------SGLICKISGFGRGP 792
Cdd:cd14208     79 VQEFVCHGALDLYLKkqQQKGPVAISWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLSregdkgSPPFIKLSDPGVSI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  793 RDRAEAVYTTMVrssllwphmllllsaiptgpmvyilalppslpglfPLVVP-CLSQPGSflrcggsgrspalwaapetl 871
Cdd:cd14208    159 KVLDEELLAERI-----------------------------------PWVAPeCLSDPQN-------------------- 183

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  872 qfghFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRncPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14208    184 ----LALEADKWGFGATLWEIFSGGHMPLSALDPSKKLQFYNDRKQLPAPH--WIELASLIQQCMSYNPLLRPSFRAI 255
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
 650-950 6.24e-16

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 79.09  E-value: 6.24e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLccgcLQLPGRQELPVAVhtLRE--GCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd14154      1 LGKGFFGQA----IKVTHRETGEVMV--MKEliRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRG-----PRDRAEAVYTT 802
Cdd:cd14154     75 GTLKDVLKDMARPLPWAQRVRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLArliveERLPSGNMSPS 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSSllwphmllllsaiptgpmvyilALPPSLPGLFPLVvpclSQPgsflrcggsgrspaLWAAPETLQFGHFSSASDV 882
Cdd:cd14154    155 ETLRH----------------------LKSPDRKKRYTVV----GNP--------------YWMAPEMLNGRSYDEKVDI 194

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  883 WSFGIVMWEVMAfgeRPYWD---MSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIH 950
Cdd:cd14154    195 FSFGIVLCEIIG---RVEADpdyLPRTKDFGLNVDSFREKFCAGCPPPFFKLAFLCCDLDPEKRPPFETLE 262
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
 668-954 1.32e-15

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 78.41  E-value: 1.32e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  668 RQELPVAVHTLREGCSDSqKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLM 747
Cdd:cd05076     41 GQELRVVLKVLDPSHHDI-ALAFFETASLMSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRKEKGHVPMAWKF 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  748 GLLPGLASAMKYLSEMGYVHRGLAARRVLLSSglickiSGFGRGprdraeavyttmvrssllwphmllllsaipTGPMVY 827
Cdd:cd05076    120 VVARQLASALSYLENKNLVHGNVCAKNILLAR------LGLEEG------------------------------TSPFIK 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  828 ilalppslpglfplvvpcLSQPGSFL----RCGGSGRSPalWAAPETLQFGH-FSSASDVWSFGIVMWEVMAFGERPYWD 902
Cdd:cd05076    164 ------------------LSDPGVGLgvlsREERVERIP--WIAPECVPGGNsLSTAADKWGFGATLLEICFNGEAPLQS 223

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  903 MSGQDVIKAVEDGFRLPPPrNCPsQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd05076    224 RTPSEKERFYQRQHRLPEP-SCP-ELATLISQCLTYEPTQRPSFRTILRDLT 273
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
985-1048 5.83e-15

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 70.38  E-value: 5.83e-15
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQ 1048
Cdd:pfam07647    3 SWSLESVADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGITSVGHRRKILKKIQELK 66
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
 689-949 6.72e-15

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 76.14  E-value: 6.72e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  689 SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHR 768
Cdd:cd05078     49 SFFEAASMMSQLSHKHLVLNYGVCVCGDENILVQEYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTLVHG 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSglickisgfgrgPRDRAeavyttmvrssllwphmllllsaipTGPMVYIlalPPSLPGLFPLVvpclsQ 848
Cdd:cd05078    129 NVCAKNILLIR------------EEDRK-------------------------TGNPPFI---KLSDPGISITV-----L 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 PGSFLRcggsGRSPalWAAPETLQFG-HFSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPPRncPSQ 927
Cdd:cd05078    164 PKDILL----ERIP--WVPPECIENPkNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPK--WTE 235

                          250       260
                   ....*....|....*....|..
gi 1958775623  928 LHRLMLECWQKDPGERPRFSQI 949
Cdd:cd05078    236 LANLINNCMDYEPDHRPSFRAI 257
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
 645-949 1.07e-14

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 75.25  E-value: 1.07e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRQelpVAVHTL-REGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd14003      3 ELGKTLGEGSFGKVKLARHKLTGEK---VAIKIIdKSKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVME 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRHH------EAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdrae 797
Cdd:cd14003     80 YASGGELFDYIVNNgrlsedEARRFFQQLI-------SAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFG-------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 avyttmvrssllwphmllllsaiptgpmvyiLAlppslpglfplvvpCLSQPGSFLR--CGgsgrSPAlWAAPETLQ-FG 874
Cdd:cd14003    145 -------------------------------LS--------------NEFRGGSLLKtfCG----TPA-YAAPEVLLgRK 174

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  875 HFSSASDVWSFGIVMWeVMAFGERPyWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14003    175 YDGPKADVWSLGVILY-AMLTGYLP-FDDDNDSKLFRKILKGKYPIPSHLSPDARDLIRRMLVVDPSKRITIEEI 247
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
 851-956 1.16e-14

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 74.83  E-value: 1.16e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  851 SFlRCGGSGRSPAlWAAPETLQFGHFS---SASDVWSFGIVMWEvMAFGERPYWDMSGQDV-IKAVEDGFRLPPPRNCPS 926
Cdd:cd14057    145 SF-QEPGKMYNPA-WMAPEALQKKPEDinrRSADMWSFAILLWE-LVTREVPFADLSNMEIgMKIALEGLRVTIPPGISP 221

                           90       100       110
                   ....*....|....*....|....*....|
gi 1958775623  927 QLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14057    222 HMCKLMKICMNEDPGKRPKFDMIVPILEKM 251
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
 644-956 1.82e-14

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 74.69  E-value: 1.82e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLccgclqLPGRQELPVAVHTLREGCSDSQKL-SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:cd14063      2 LEIKEVIGKGRFGRV------HRGRWHGDVAIKLLNIDYLNEEQLeAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVT 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICkISGFGrgprdraeavytT 802
Cdd:cd14063     76 SLCKGRTLYSLIHERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFG------------L 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSSLLWPHMLLLLSAIPTGPMVYilalppslpgLFPLVVPCLSQPgsflrcggsgrspalWAAPETLQFghfSSASDV 882
Cdd:cd14063    143 FSLSGLLQPGRREDTLVIPNGWLCY----------LAPEIIRALSPD---------------LDFEESLPF---TKASDV 194

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  883 WSFGIVMWEVMAfGERPYWDMSGQDVIKAVEDGFRLPPPR-NCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14063    195 YAFGTVWYELLA-GRWPFKEQPAESIIWQVGCGKKQSLSQlDIGREVKDILMQCWAYDPEKRPTFSDLLRMLERL 268
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
 697-956 3.41e-14

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 73.96  E-value: 3.41e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYL-SEMGYVHRGLAARRV 775
Cdd:cd13992     50 LKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKMDWMFKSSFIKDIVKGMNYLhSSSIGYHGRLKSSNC 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  776 LLSSGLICKISGFG-RGPRDRAEAVYttmvrssllwphmlllLSAIPTGPMVyilalppslpglfplvvpclsqpgsflr 854
Cdd:cd13992    130 LVDSRWVVKLTDFGlRNLLEEQTNHQ----------------LDEDAQHKKL---------------------------- 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  855 cggsgrspaLWAAPETL------QFGhfSSASDVWSFGIVMWEvMAFGERPyWDMSGQD--VIKAVEDGFRLPPPR---- 922
Cdd:cd13992    166 ---------LWTAPELLrgslleVRG--TQKGDVYSFAIILYE-ILFRSDP-FALEREVaiVEKVISGGNKPFRPElavl 232

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1958775623  923 --NCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd13992    233 ldEFPPRLVLLVKQCWAENPEKRPSFKQIKKTLTEN 268
SAM_EPH-B4 cd09554
SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 987-1050 4.96e-14

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.


Pssm-ID: 188953  Cd Length: 67  Bit Score: 67.58  E-value: 4.96e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  987 SFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTR 1050
Cdd:cd09554      2 SCGSVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLRMGVTLAGHQKKILSSIQAMGIQ 65
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
 682-956 1.16e-13

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 72.67  E-value: 1.16e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  682 CSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAeLVTAQLMGLLPGLASAMKYLS 761
Cdd:cd14222     29 CDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLRADDP-FPWQQKVSFAKGIASGMAYLH 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  762 EMGYVHRGLAARRVLLSSGLICKISGFG----------RGPRDRAEAVYTTMVRSSLLWPhmllllsaiptgpmvYILAL 831
Cdd:cd14222    108 SMSIIHRDLNSHNCLIKLDKTVVVADFGlsrliveekkKPPPDKPTTKKRTLRKNDRKKR---------------YTVVG 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  832 PPslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSFGIVMWEVMA--------------FG- 896
Cdd:cd14222    173 NP------------------------------YWMAPEMLNGKSYDEKVDIFSFGIVLCEIIGqvyadpdclprtldFGl 222

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  897 -ERPYWDmsgqdviKAVedgfrlppPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14222    223 nVRLFWE-------KFV--------PKDCPPAFFPLAAICCRLEPDSRPAFSKLEDSFEAL 268
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
 984-1050 1.43e-13

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 66.55  E-value: 1.43e-13
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623   984 AFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTR 1050
Cdd:smart00454    2 SQWSPESVADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGITKLGHRKKILKAIQKLKEQ 68
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
 864-956 1.53e-13

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 72.24  E-value: 1.53e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  864 LWAAPETLQFGHFSSA----SDVWSFGIVMWEvMAFGERPYW----DMSGQDVIKAVEDGFRLPPPR------NCPSQLH 929
Cdd:cd14042    171 LWTAPELLRDPNPPPPgtqkGDVYSFGIILQE-IATRQGPFYeegpDLSPKEIIKKKVRNGEKPPFRpsldelECPDEVL 249

                           90       100
                   ....*....|....*....|....*..
gi 1958775623  930 RLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14042    250 SLMQRCWAEDPEERPDFSTLRNKLKKL 276
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
 987-1047 3.33e-13

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 65.37  E-value: 3.33e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  987 SFGSVGAWLEALDLCRYKDNFSAaGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:pfam00536    4 SVEDVGEWLESIGLGQYIDSFRA-GYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
 692-944 5.41e-13

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 70.49  E-value: 5.41e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  692 AEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHH---EAELVTAQLMGLLPGLAsamkYLSEMGYVHR 768
Cdd:cd06629     57 SEIDTLKDLDHPNIVQYLGFEETEDYFSIFLEYVPGGSIGSCLRKYgkfEEDLVRFFTRQILDGLA----YLHSKGILHR 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSGLICKISGFGRGPrdRAEAVYTTmvrssllwphmllllsaiptgpmvyilalppslpglfplvVPCLSQ 848
Cdd:cd06629    133 DLKADNILVDLEGICKISDFGISK--KSDDIYGN----------------------------------------NGATSM 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 PGSFlrcggsgrspaLWAAPETLQFGH--FSSASDVWSFGIVMWEVMAfGERPYWDMsgqDVIKAVedgFRL-------- 918
Cdd:cd06629    171 QGSV-----------FWMAPEVIHSQGqgYSAKVDIWSLGCVVLEMLA-GRRPWSDD---EAIAAM---FKLgnkrsapp 232

                          250       260
                   ....*....|....*....|....*..
gi 1958775623  919 -PPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd06629    233 vPEDVNLSPEALDFLNACFAIDPRDRP 259
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 646-949 6.24e-13

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 70.14  E-value: 6.24e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGDL-CCGCLQLPGRQELPV----AVHTLREgcsdSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMI 720
Cdd:cd08222      4 VVRKLGSGNFGTVyLVSDLKATADEELKVlkeiSVGELQP----DETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  721 VTEYMNLGALDDFL---RHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLIcKISGFG-----RGP 792
Cdd:cd08222     80 VTEYCEGGDLDDKIseyKKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNVI-KVGDFGisrilMGT 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  793 RDRAeavyTTMvrssllwphmllllsaipTGPMVYIlalppslpglfplvvpclsqpgsflrcggsgrspalwaAPETLQ 872
Cdd:cd08222    159 SDLA----TTF------------------TGTPYYM--------------------------------------SPEVLK 178

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  873 FGHFSSASDVWSFGIVMWEVM----AFgerpywdmSGQD----VIKAVEDgfRLPP-PRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd08222    179 HEGYNSKSDIWSLGCILYEMCclkhAF--------DGQNllsvMYKIVEG--ETPSlPDKYSKELNAIYSRMLNKDPALR 248


                   ....*.
gi 1958775623  944 PRFSQI 949
Cdd:cd08222    249 PSAAEI 254
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
 682-949 1.23e-12

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 69.45  E-value: 1.23e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  682 CSDSQKlSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAEL-VTAQ-LMGLLPGlasaMKY 759
Cdd:cd14027     31 CIEHNE-ALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVSVPLsVKGRiILEIIEG----MAY 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  760 LSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRaeavYTTMVRSSLLWPHMLLLLSAIPTGPMVYIlalppslpglf 839
Cdd:cd14027    106 LHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKM----WSKLTKEEHNEQREVDGTAKKNAGTLYYM----------- 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  840 plvvpclsqpgsflrcggsgrspalwaAPETLQFGHFSSA--SDVWSFGIVMWEVMAfGERPYWDMSGQD-VIKAVEDGF 916
Cdd:cd14027    171 ---------------------------APEHLNDVNAKPTekSDVYSFAIVLWAIFA-NKEPYENAINEDqIIMCIKSGN 222

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1958775623  917 RlPP----PRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14027    223 R-PDvddiTEYCPREIIDLMKLCWEANPEARPTFPGI 258
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
 718-958 1.33e-12

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 69.36  E-value: 1.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAE 797
Cdd:cd14043     71 LAIVSEHCSRGSLEDLLRNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQ 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVyttmvrssllwphmllllsaiptgpmvyilALPPSLPGlfplvvpclsqpgsflrcggsgrsPALWAAPETLQ----F 873
Cdd:cd14043    151 NL------------------------------PLPEPAPE------------------------ELLWTAPELLRdprlE 176

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  874 GHFSSASDVWSFGIVMWEVMAFGErPY--WDMSGQDVIKAVedgfRLPPP--------RNCPSQLHRLMLECWQKDPGER 943
Cdd:cd14043    177 RRGTFPGDVFSFAIIMQEVIVRGA-PYcmLGLSPEEIIEKV----RSPPPlcrpsvsmDQAPLECIQLMKQCWSEAPERR 251

                          250
                   ....*....|....*
gi 1958775623  944 PRFSQIHSILSKMGQ 958
Cdd:cd14043    252 PTFDQIFDQFKSINK 266
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
 668-948 1.34e-12

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 69.27  E-value: 1.34e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  668 RQELPVAVHTL-REGCSDSQKLsFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrHHEAELVTAQL 746
Cdd:cd14202     26 KHDLEVAVKCInKKNLAKSQTL-LGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLADYL-HTMRTLSEDTI 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  747 MGLLPGLASAMKYLSEMGYVHRGLAARRVLLS---------SGLICKISGFGRGPRDRAEAVYTTMvrssllwphmllll 817
Cdd:cd14202    104 RLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksnpNNIRIKIADFGFARYLQNNMMAATL-------------- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  818 saiptgpmvyilalppslpglfplvvpclsqpgsflrCGgsgrSPaLWAAPETLQFGHFSSASDVWSFGIVMWEVMAfGE 897
Cdd:cd14202    170 -------------------------------------CG----SP-MYMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GK 206

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  898 RPYWDMSGQDVIKAVEDGFRLPP--PRNCPSQLHRLMLECWQKDPGERPRFSQ 948
Cdd:cd14202    207 APFQASSPQDLRLFYEKNKSLSPniPRETSSHLRQLLLGLLQRNQKDRMDFDE 259
SAM_EPH-B1 cd09551
SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 985-1050 1.50e-12

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.


Pssm-ID: 188950  Cd Length: 68  Bit Score: 63.52  E-value: 1.50e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTR 1050
Cdd:cd09551      3 FTAFTSVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQMTSEDLLRIGVTLAGHQKKILNSIQSMRVQ 68
SAM_EPH-B6 cd09555
SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 985-1048 3.08e-12

SAM domain of EPH-B6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B6 receptors and appears to mediate cell-cell initiated signal transduction. Receptors of this type are highly expressed in embryo and adult nervous system, in thymus and also in T-cells. They are involved in regulation of cell adhesion and migration. (EPH-B6 receptor is unusual; it fails to show catalytic activity due to alteration in kinase domain). EPH-B6 may be considered as a biomarker in some types of tumors; EPH-B6 activates MAP kinase signaling in lung adenocarcinoma, suppresses metastasis formation in non-small cell lung cancer, and slows invasiveness in some breast cancer cell lines.


Pssm-ID: 188954  Cd Length: 69  Bit Score: 62.64  E-value: 3.08e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQ 1048
Cdd:cd09555      3 FPCLDSPQAWLSAIGLECYQDNFSKFGLCTFSDVAQLSLEDLPALGITLAGHQKKLLHHIQLLQ 66
SAM_EPH-B3 cd09553
SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 985-1051 3.16e-12

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.


Pssm-ID: 188952  Cd Length: 69  Bit Score: 62.74  E-value: 3.16e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  985 FPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09553      3 YTTFTTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRIGVTLAGHQKKILSSIQDMRLQM 69
SAM_EPH-A8 cd09550
SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 990-1051 3.80e-12

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.


Pssm-ID: 188949  Cd Length: 65  Bit Score: 62.19  E-value: 3.80e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09550      4 SVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRMNIEDIRRLGITLMGHQKKILTSIQVMRAQL 65
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
 696-949 4.61e-12

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 67.59  E-value: 4.61e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  696 TLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHH------EAELVTAQLmgllpglASAMKYLSEMGYVHRG 769
Cdd:cd14080     55 ILRKLRHPNIIQVYSIFERGSKVFIFMEYAEHGDLLEYIQKRgalsesQARIWFRQL-------ALAVQYLHSLDIAHRD 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  770 LAARRVLLSSGLICKIS--GFGR--GPRDRAEavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpc 845
Cdd:cd14080    128 LKCENILLDSNNNVKLSdfGFARlcPDDDGDV------------------------------------------------ 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  846 LSQpgSFlrCGgsgrSPAlWAAPETLQfG--HFSSASDVWSFGIVMWeVMAFGERPYWDMSGQDVIKA-VEDGFRLPPPR 922
Cdd:cd14080    160 LSK--TF--CG----SAA-YAAPEILQ-GipYDPKKYDIWSLGVILY-IMLCGSMPFDDSNIKKMLKDqQNRKVRFPSSV 228

                          250       260
                   ....*....|....*....|....*...
gi 1958775623  923 NCPS-QLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14080    229 KKLSpECKDLIDQLLEPDPTKRATIEEI 256
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
 675-956 1.05e-11

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 66.35  E-value: 1.05e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  675 VHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAeLVTAQLMGLLPGLA 754
Cdd:cd14155     20 VMALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQLLDSNEP-LSWTVRVKLALDIA 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  755 SAMKYLSEMGYVHRGLAARRVLLSsglickisgfgrgprdRAEAVYTTMVrssllwphmllllsaiptgpmvyilalpps 834
Cdd:cd14155     99 RGLSYLHSKGIFHRDLTSKNCLIK----------------RDENGYTAVV------------------------------ 132

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  835 lpGLFPLV--VPCLSQPGSFLRCGGSgrspALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGER-----PYWDMSGQD 907
Cdd:cd14155    133 --GDFGLAekIPDYSDGKEKLAVVGS----PYWMAPEVLRGEPYNEKADVFSYGIILCEIIARIQAdpdylPRTEDFGLD 206

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1958775623  908 VikaveDGFRLPPPrNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14155    207 Y-----DAFQHMVG-DCPPDFLQLAFNCCNMDPKSRPSFHDIVKTLEEI 249
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
 673-951 1.11e-11

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 66.57  E-value: 1.11e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTL-REGCSDSQKLsFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHhEAELVTAQLMGLLP 751
Cdd:cd14201     35 VAIKSInKKNLSKSQIL-LGKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGGDLADYLQA-KGTLSEDTIRVFLQ 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  752 GLASAMKYLSEMGYVHRGLAARRVLLS---------SGLICKISGFGrgprdRAEAVYTTMVRSSLlwphmllllsaipt 822
Cdd:cd14201    113 QIAAAMRILHSKGIIHRDLKPQNILLSyasrkkssvSGIRIKIADFG-----FARYLQSNMMAATL-------------- 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  823 gpmvyilalppslpglfplvvpclsqpgsflrCGgsgrSPaLWAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWD 902
Cdd:cd14201    174 --------------------------------CG----SP-MYMAPEVIMSQHYDAKADLWSIGTVIYQCLV-GKPPFQA 215

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  903 MSGQDVIKAVEDGFRLPP--PRNCPSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd14201    216 NSPQDLRMFYEKNKNLQPsiPRETSPYLADLLLGLLQRNQKDRMDFEAFFS 266
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
 682-951 1.38e-11

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 66.36  E-value: 1.38e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  682 CSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTrgNPLMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYLS 761
Cdd:cd14025     34 VDDSERMELLEEAKKMEMAKFRHILPVYGICS--EPVGLVMEYMETGSLEKLLASEP--LPWELRFRIIHETAVGMNFLH 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  762 EMG--YVHRGLAARRVLLSSGLICKISGFGRGprdRAEAVYTTMVRSSLLWPhmllllsaiptGPMVYIlalPPSlpglf 839
Cdd:cd14025    110 CMKppLLHLDLKPANILLDAHYHVKISDFGLA---KWNGLSHSHDLSRDGLR-----------GTIAYL---PPE----- 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  840 plvvpclsqpgsflRCGGSGRSPalwaapetlqfghfSSASDVWSFGIVMWEVMAfGERPYWDMSG-QDVIKAVEDGFR- 917
Cdd:cd14025    168 --------------RFKEKNRCP--------------DTKHDVYSFAIVIWGILT-QKKPFAGENNiLHIMVKVVKGHRp 218

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1958775623  918 -LPP-----PRNCpSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd14025    219 sLSPiprqrPSEC-QQMICLMKRCWDQDPRKRPTFQDITS 257
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
 646-944 1.95e-11

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 65.36  E-value: 1.95e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKsLGAGRFGDLCcGCLQLPGRQELPVAVHTLREGCSDSQKlsflaEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd06612      8 LEK-LGEGSYGSVY-KAIHKETGQVVAIKVVPVEEDLQEIIK-----EISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRHHEAELVTAQ----LMGLLPGLAsamkYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyt 801
Cdd:cd06612     81 GAGSVSDIMKITNKTLTEEEiaaiLYQTLKGLE----YLHSNKKIHRDIKAGNILLNEEGQAKLADFG------------ 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 tmvrssllwphmlllLSAIptgpMVYILALPPSLPGlfplvvpclsqpgsflrcggsgrSPaLWAAPETLQFGHFSSASD 881
Cdd:cd06612    145 ---------------VSGQ----LTDTMAKRNTVIG-----------------------TP-FWMAPEVIQEIGYNNKAD 181

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  882 VWSFGIVMWEvMAFGERPYWDMSGQDVIKAVedGFRLPP----PRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd06612    182 IWSLGITAIE-MAEGKPPYSDIHPMRAIFMI--PNKPPPtlsdPEKWSPEFNDFVKKCLVKDPEERP 245
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
 648-944 2.39e-11

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 65.31  E-value: 2.39e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd06623      7 KVLGQGSSGVVYKVRHKPTGKI---YALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHEA------ELVTAQLmglLPGLAsamkYL-SEMGYVHRGLAARRVLLSS-GLIcKISGFGrgprdraeaV 799
Cdd:cd06623     84 GSLADLLKKVGKipepvlAYIARQI---LKGLD----YLhTKRHIIHRDIKPSNLLINSkGEV-KIADFG---------I 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  800 YTTMVRSsllwphmllllsaiptgpmvyilalppslpglfplVVPCLSQPGSflrcggsgrspALWAAPETLQFGHFSSA 879
Cdd:cd06623    147 SKVLENT-----------------------------------LDQCNTFVGT-----------VTYMSPERIQGESYSYA 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  880 SDVWSFGIVMWEvMAFGERPY--------WDMsgqdvIKAVEDGFRLPPPRNCPSQLHRLMLE-CWQKDPGERP 944
Cdd:cd06623    181 ADIWSLGLTLLE-CALGKFPFlppgqpsfFEL-----MQAICDGPPPSLPAEEFSPEFRDFISaCLQKDPKKRP 248
SAM_EPH-B2 cd09552
SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 984-1053 3.03e-11

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.


Pssm-ID: 188951  Cd Length: 71  Bit Score: 60.02  E-value: 3.03e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  984 AFPSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRVLQ 1053
Cdd:cd09552      2 DYTSFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRVGVTLAGHQKKILNSIQVMRAQMNQ 71
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
 683-949 5.29e-11

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 64.33  E-value: 5.29e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  683 SDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA-------ELVTAQLMGLLPGLas 755
Cdd:cd08530     39 SQKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPFGDLSKLISKRKKkrrlfpeDDIWRIFIQMLRGL-- 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  756 amKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrssllwphmlllLSAIPTGPMVYilalppsl 835
Cdd:cd08530    117 --KALHDQKILHRDLKSANILLSAGDLVKIGDLG---------------------------ISKVLKKNLAK-------- 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  836 pglfplvvpclSQPGSflrcggsgrspALWAAPETLQFGHFSSASDVWSFGIVMWEVMAFgERPYWDMSGQDVIKAVEDG 915
Cdd:cd08530    160 -----------TQIGT-----------PLYAAPEVWKGRPYDYKSDIWSLGCLLYEMATF-RPPFEARTMQELRYKVCRG 216

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1958775623  916 fRLPPPRNCPSQ-LHRLMLECWQKDPGERPRFSQI 949
Cdd:cd08530    217 -KFPPIPPVYSQdLQQIIRSLLQVNPKKRPSCDKL 250
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 451-551 5.48e-11

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 59.82  E-value: 5.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  451 PGAPweeDEIRRDRVEPQSVSLSWREPVPAGASGTNrteYEIRYYEKGQSE-QTYSTVKTGAPAVTVTNLKPATRYVFQI 529
Cdd:cd00063      1 PSPP---TNLRVTDVTSTSVTLSWTPPEDDGGPITG---YVVEYREKGSGDwKEVEVTPGSETSYTLTGLKPGTEYEFRV 74

                           90       100
                   ....*....|....*....|...
gi 1958775623  530 RAASP-GPSweaqSFSPSIEVQT 551
Cdd:cd00063     75 RAVNGgGES----PPSESVTVTT 93
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 451-531 6.98e-11

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 59.55  E-value: 6.98e-11
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   451 PGAPWEedeIRRDRVEPQSVSLSWREPVPAGASGtNRTEYEIRYYEKGQSEQTYsTVKTGAPAVTVTNLKPATRYVFQIR 530
Cdd:smart00060    1 PSPPSN---LRVTDVTSTSVTLSWEPPPDDGITG-YIVGYRVEYREEGSEWKEV-NVTPSSTSYTLTGLKPGTEYEFRVR 75


                    .
gi 1958775623   531 A 531
Cdd:smart00060   76 A 76
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
 650-893 1.01e-10

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 64.06  E-value: 1.01e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGClqlpgRQELPVAVHTLREGCSDS---QKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMN 726
Cdd:cd14158     23 LGEGGFGVVFKGY-----INDKNVAVKKLAAMVDIStedLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMP 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  727 LGALDDFL--RHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGprdRAEAVYTTMV 804
Cdd:cd14158     98 NGSLLDRLacLNDTPPLSWHMRCKIAQGTANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLA---RASEKFSQTI 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  805 RSSLLwphmllllsaipTGPMVYIlalppslpglfplvvpclsqpgsflrcggsgrspalwaAPETLQfGHFSSASDVWS 884
Cdd:cd14158    175 MTERI------------VGTTAYM--------------------------------------APEALR-GEITPKSDIFS 203


                   ....*....
gi 1958775623  885 FGIVMWEVM 893
Cdd:cd14158    204 FGVVLLEII 212
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
 689-956 1.52e-10

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 63.05  E-value: 1.52e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  689 SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHR 768
Cdd:cd14221     36 TFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMNIIHR 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSGLICKISGFgrgprdraeavyttmvrssllwphmllllsaiptgpmvyilalppslpGLFPLVVPCLSQ 848
Cdd:cd14221    116 DLNSHNCLVRENKSVVVADF------------------------------------------------GLARLMVDEKTQ 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 PGSFLRCGGSGRSP-------ALWAAPETLQFGHFSSASDVWSFGIVMWEVMA-FGERPYWDMSGQDVIKAVEdGF--RL 918
Cdd:cd14221    148 PEGLRSLKKPDRKKrytvvgnPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGrVNADPDYLPRTMDFGLNVR-GFldRY 226

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1958775623  919 PPPrNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14221    227 CPP-NCPPSFFPIAVLCCDLDPEKRPSFSKLEHWLETL 263
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
 650-944 2.43e-10

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 62.76  E-value: 2.43e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGclqLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd06640     12 IGKGSFGEVFKG---IDNRTQQVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGS 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRhhEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGprdrAEAVYTTMVRSSll 809
Cdd:cd06640     89 ALDLLR--AGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVA----GQLTDTQIKRNT-- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvyILALPpslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd06640    161 ------------------FVGTP-------------------------------FWMAPEVIQQSAYDSKADIWSLGITA 191

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  890 WEvMAFGERPYWDMSGQDVIkavedgFRLP--PPRNCPSQLHRLMLE----CWQKDPGERP 944
Cdd:cd06640    192 IE-LAKGEPPNSDMHPMRVL------FLIPknNPPTLVGDFSKPFKEfidaCLNKDPSFRP 245
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
 668-946 2.55e-10

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 62.39  E-value: 2.55e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  668 RQELPVAVHTL-REGCSDSQKLsfLA-EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrHHEAELVTAQ 745
Cdd:cd14120     17 KPDLPVAIKCItKKNLSKSQNL--LGkEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLADYL-QAKGTLSEDT 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  746 LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLS---------SGLICKISGFGRgprdraeAVYttmvrssllwphmlll 816
Cdd:cd14120     94 IRVFLQQIAAAMKALHSKGIVHRDLKPQNILLShnsgrkpspNDIRLKIADFGF-------ARF---------------- 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  817 lsaIPTGPMVYILalppslpglfplvvpclsqpgsflrCGgsgrSPaLWAAPETLQFGHFSSASDVWSFGIVMWEVMAfG 896
Cdd:cd14120    151 ---LQDGMMAATL-------------------------CG----SP-MYMAPEVIMSLQYDAKADLWSIGTIVYQCLT-G 196

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  897 ERPYWDMSGQDVIKAVEDGFRLPP--PRNCPSQLHRLMLECWQKDPGERPRF 946
Cdd:cd14120    197 KAPFQAQTPQELKAFYEKNANLRPniPSGTSPALKDLLLGLLKRNPKDRIDF 248
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
 702-944 3.17e-10

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 61.84  E-value: 3.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  702 HSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGL 781
Cdd:cd06614     55 HPNIVDYYDSYLVGDELWVVMEYMDGGSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDG 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  782 ICKISGFG--------RGPRdraeavyTTMVrssllwphmllllsaiptGpmvyilalppslpglfplvvpclsqpgsfl 853
Cdd:cd06614    135 SVKLADFGfaaqltkeKSKR-------NSVV------------------G------------------------------ 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  854 rcggsgrSPAlWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGF--RLPPPRNCPSQLHRL 931
Cdd:cd06614    160 -------TPY-WMAPEVIKRKDYGPKVDIWSLGIMCIE-MAEGEPPYLEEPPLRALFLITTKGipPLKNPEKWSPEFKDF 230

                          250
                   ....*....|...
gi 1958775623  932 MLECWQKDPGERP 944
Cdd:cd06614    231 LNKCLVKDPEKRP 243
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
 645-944 4.00e-10

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 61.72  E-value: 4.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGdLCCGCLQLPGRQElpVAVHTL-REGCSDSQKLSFLAEALTLGQFDHSHIVRLEGV-VTRGNpLMIVT 722
Cdd:cd05117      3 ELGKVLGRGSFG-VVRLAVHKKTGEE--YAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKN-LYLVM 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDD------FLRHHEAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRVLLSS---GLICKISGFGrgpr 793
Cdd:cd05117     79 ELCTGGELFDrivkkgSFSEREAAKIMKQIL-------SAVAYLHSQGIVHRDLKPENILLASkdpDSPIKIIDFG---- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  794 draeavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpcLS---QPGSFLR--CGgsgrSPaLWAAP 868
Cdd:cd05117    148 ----------------------------------------------------LAkifEEGEKLKtvCG----TP-YYVAP 170

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  869 ETLQFGHFSSASDVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDG-FRLPPPR-NCPSQ----LHRLMLecwQKDPGE 942
Cdd:cd05117    171 EVLKGKGYGKKCDIWSLGVILY-ILLCGYPPFYGETEQELFEKILKGkYSFDSPEwKNVSEeakdLIKRLL---VVDPKK 246


                   ..
gi 1958775623  943 RP 944
Cdd:cd05117    247 RL 248
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
 683-952 4.34e-10

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 61.32  E-value: 4.34e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  683 SDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA--ELVT-AQLMGLLPGLASAMKY 759
Cdd:cd08215     39 SEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDLAQKIKKQKKkgQPFPeEQILDWFVQICLALKY 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  760 LSEMGYVHRGLAARRVLLSSGLICKISGFG-----RGPRDRAeavyTTMVrssllwphmllllsaiptG-PMvYilaLPP 833
Cdd:cd08215    119 LHSRKILHRDLKTQNIFLTKDGVVKLGDFGiskvlESTTDLA----KTVV------------------GtPY-Y---LSP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  834 SLpglfplvvpCLSQPgsflrcggsgrspalwaapetlqfghFSSASDVWSFGIVMWEVMAFgERPY--WDMSGQdVIKA 911
Cdd:cd08215    173 EL---------CENKP--------------------------YNYKSDIWALGCVLYELCTL-KHPFeaNNLPAL-VYKI 215

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1958775623  912 VEDGFRlPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSI 952
Cdd:cd08215    216 VKGQYP-PIPSQYSSELRDLVNSMLQKDPEKRPSANEILSS 255
SAM_EPH-A6 cd09547
SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 986-1048 4.55e-10

SAM domain of EPH-A6 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A6 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers.


Pssm-ID: 188946  Cd Length: 64  Bit Score: 56.43  E-value: 4.55e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  986 PSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQ 1048
Cdd:cd09547      1 PLFVTVSDWLDSIKMGQYKNNFMAAGFTTLDMVSRMTIDDIRRIGVTLIGHQRRIVSSIQTLR 63
SAM_EPH-A5 cd09546
SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 990-1051 7.37e-10

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.


Pssm-ID: 188945  Cd Length: 66  Bit Score: 56.09  E-value: 7.37e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09546      5 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVTLVGHQKKIMNSIQEMRVQL 66
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
 684-951 1.03e-09

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 61.16  E-value: 1.03e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  684 DSQKLSFL-AEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA----ELVTAQLmglLPGLASAMK 758
Cdd:cd08216     39 SKEDLKFLqQEILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMAYGSCRDLLKTHFPeglpELAIAFI---LRDVLNALE 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  759 YLSEMGYVHRGLAARRVLLSSGLICKISGF-------GRGPRDRAeavyttmvrssllwphmllllsaiptgpmvyILAL 831
Cdd:cd08216    116 YIHSKGYIHRSVKASHILISGDGKVVLSGLryaysmvKHGKRQRV-------------------------------VHDF 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  832 PPSLPGLFPlvvpclsqpgsflrcggsgrspalWAAPETLQ--FGHFSSASDVWSFGIVMWEvMAFGERPYWDM------ 903
Cdd:cd08216    165 PKSSEKNLP------------------------WLSPEVLQqnLLGYNEKSDIYSVGITACE-LANGVVPFSDMpatqml 219

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  904 ----SG--------------QDVIKAVEDGFRLPP----PRNCPSQ------LHRLMLECWQKDPGERPRFSQI--HS 951
Cdd:cd08216    220 lekvRGttpqlldcstypleEDSMSQSEDSSTEHPnnrdTRDIPYQrtfseaFHQFVELCLQRDPELRPSASQLlaHS 297
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
 697-949 1.44e-09

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 60.11  E-value: 1.44e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA---ELVTAQLMGLLPGLAsamkYLSEMGYVHRGLAAR 773
Cdd:cd06632     56 LSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSIHKLLQRYGAfeePVIRLYTRQILSGLA----YLHSRNTVHRDIKGA 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  774 RVLLSSGLICKISGFGrgprdraeavyttMVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFL 853
Cdd:cd06632    132 NILVDTNGVVKLADFG-------------MAKH---------------------------------------VEAFSFAK 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  854 RCGGSgrspALWAAPETL--QFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGFRLPP-PRNCPSQLHR 930
Cdd:cd06632    160 SFKGS----PYWMAPEVImqKNSGYGLAVDIWSLGCTVLE-MATGKPPWSQYEGVAAIFKIGNSGELPPiPDHLSPDAKD 234

                          250
                   ....*....|....*....
gi 1958775623  931 LMLECWQKDPGERPRFSQI 949
Cdd:cd06632    235 FIRLCLQRDPEDRPTASQL 253
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
 691-948 1.98e-09

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 59.61  E-value: 1.98e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  691 LAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAeLVTAQLMGLLPGLASAMKYLSEMGYVHRGL 770
Cdd:cd14121     43 LTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRRT-LPESTVRRFLQQLASALQFLREHNISHMDL 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  771 AARRVLLSSGL--ICKISGFG----RGPRDRAeavytTMVRSSllwphmllllsaiPtgpmvyilalppslpglfplvvp 844
Cdd:cd14121    122 KPQNLLLSSRYnpVLKLADFGfaqhLKPNDEA-----HSLRGS-------------P----------------------- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  845 clsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSFGIVMWEVMaFGERPYWDMSgqdvIKAVEDGFRLPPP--- 921
Cdd:cd14121    161 -------------------LYMAPEMILKKKYDARVDLWSVGVILYECL-FGRAPFASRS----FEELEEKIRSSKPiei 216

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1958775623  922 -------RNCPSQLHRLMlecwQKDPGERPRFSQ 948
Cdd:cd14121    217 ptrpelsADCRDLLLRLL----QRDPDRRISFEE 246
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
 684-949 2.19e-09

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 59.45  E-value: 2.19e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  684 DSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEM 763
Cdd:cd14156     29 DVDQHKIVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLAREELPLSWREKVELACDISRGMVYLHSK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  764 GYVHRGLAARRVLLSsglickisgfgRGPRDRaEAVYTTMvrssllwphmllllsaiptGPMVYILALPPSLPGlfplvv 843
Cdd:cd14156    109 NIYHRDLNSKNCLIR-----------VTPRGR-EAVVTDF-------------------GLAREVGEMPANDPE------ 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  844 PCLSQPGSflrcggsgrspALWAAPETLQFGHFSSASDVWSFGIVMWEVMAF-----GERPYWDMSGQDVikaveDGFRL 918
Cdd:cd14156    152 RKLSLVGS-----------AFWMAPEMLRGEPYDRKVDVFSFGIVLCEILARipadpEVLPRTGDFGLDV-----QAFKE 215

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1958775623  919 PPPrNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14156    216 MVP-GCPEPFLDLAASCCRMDAFKRPSFAEL 245
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
 697-949 2.42e-09

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 59.32  E-value: 2.42e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQfdHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAE--LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARR 774
Cdd:cd13997     56 LGQ--HPNIVRYYSSWEEGGHLYIQMELCENGSLQDALEELSPIskLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDN 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  775 VLLSSGLICKISGFGrgprdraeavyttmvrssllwphmllLLSAIPTGPMVYilalppslpglfplvvpclsqpgsflr 854
Cdd:cd13997    134 IFISNKGTCKIGDFG--------------------------LATRLETSGDVE--------------------------- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  855 cGGSGRspalWAAPETLQ-FGHFSSASDVWSFGIVMWEVMAFGERPYwdmSGQDVIKAVEDGFRLPPPRNCPSQLHRLML 933
Cdd:cd13997    161 -EGDSR----YLAPELLNeNYTHLPKADIFSLGVTVYEAATGEPLPR---NGQQWQQLRQGKLPLPPGLVLSQELTRLLK 232

                          250
                   ....*....|....*.
gi 1958775623  934 ECWQKDPGERPRFSQI 949
Cdd:cd13997    233 VMLDPDPTRRPTADQL 248
SAM_EPH-A2 cd09543
SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of ...
 988-1051 2.84e-09

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.


Pssm-ID: 188942  Cd Length: 70  Bit Score: 54.46  E-value: 2.84e-09
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  988 FGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQTRV 1051
Cdd:cd09543      5 FRTVAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGVRLPGHQKRIAYSILGLKEQV 68
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
 672-946 2.95e-09

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 59.55  E-value: 2.95e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  672 PVAVHTLR--EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrhHEAELVTAQLMGL 749
Cdd:cd14026     24 TVAIKCLKldSPVGDSERNCLLKEAEILHKARFSYILPILGICNEPEFLGIVTEYMTNGSLNELL--HEKDIYPDVAWPL 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  750 ----LPGLASAMKYLSEMG--YVHRGLAARRVLLSSGLICKISGFGrgpRDRAEAVYTTMVRSSllwphmlllLSAIPTG 823
Cdd:cd14026    102 rlriLYEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFG---LSKWRQLSISQSRSS---------KSAPEGG 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  824 PMVYilaLPPSlpglfplvvpcLSQPGSFLRCggsgrspalwaapetlqfghfSSASDVWSFGIVMWEVMAfGERPYWDM 903
Cdd:cd14026    170 TIIY---MPPE-----------EYEPSQKRRA---------------------SVKHDIYSYAIIMWEVLS-RKIPFEEV 213

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  904 SGQ-DVIKAVEDGFRL-----PPPRNCPSQ--LHRLMLECWQKDPGERPRF 946
Cdd:cd14026    214 TNPlQIMYSVSQGHRPdtgedSLPVDIPHRatLINLIESGWAQNPDERPSF 264
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
 684-949 4.62e-09

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 58.60  E-value: 4.62e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  684 DSQKLS-FLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSE 762
Cdd:cd06611     42 SEEELEdFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGALDSIMLELERGLTEPQIRYVCRQMLEALNFLHS 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  763 MGYVHRGLAARRVLLSSGLICKISGFGRGPRDRaeavyTTMVRSSllwphmllllSAIPTgPmvYILAlppslpglfPLV 842
Cdd:cd06611    122 HKVIHRDLKAGNILLTLDGDVKLADFGVSAKNK-----STLQKRD----------TFIGT-P--YWMA---------PEV 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  843 VPClsqpgsflrcggsgrspalwaapETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGfrLPP-- 920
Cdd:cd06611    175 VAC-----------------------ETFKDNPYDYKADIWSLGITLIE-LAQMEPPHHELNPMRVLLKILKS--EPPtl 228

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1958775623  921 --PRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd06611    229 dqPSKWSSSFNDFLKSCLVKDPDDRPTAAEL 259
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
 693-944 5.78e-09

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 58.14  E-value: 5.78e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRH-------HEAELVTAqLMGLLPGLAsamkYLSEMGY 765
Cdd:cd06610     49 EIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLLDIMKSsyprgglDEAIIATV-LKEVLKGLE----YLHSNGQ 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  766 VHRGLAARRVLLSSGLICKISGFGRG-----PRDRAEAVYTTMVRSsllwphmllllsaiptgpmvyilalppslpglfp 840
Cdd:cd06610    124 IHRDVKAGNILLGEDGSVKIADFGVSaslatGGDRTRKVRKTFVGT---------------------------------- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  841 lvvPClsqpgsflrcggsgrspalWAAPETLQFGH-FSSASDVWSFGIVMWEvMAFGERPYWDmsgqdvikavedgfrLP 919
Cdd:cd06610    170 ---PC-------------------WMAPEVMEQVRgYDFKADIWSFGITAIE-LATGAAPYSK---------------YP 211

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1958775623  920 PPR-------NCPSQLH------------RLMLE-CWQKDPGERP 944
Cdd:cd06610    212 PMKvlmltlqNDPPSLEtgadykkysksfRKMISlCLQKDPSKRP 256
fn3 pfam00041
Fibronectin type III domain;
469-533 1.00e-08

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 53.19  E-value: 1.00e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  469 SVSLSWREPVPAGASGTNrteYEIRYYEKG-QSEQTYSTVKTGAPAVTVTNLKPATRYVFQIRAAS 533
Cdd:pfam00041   15 SLTVSWTPPPDGNGPITG---YEVEYRPKNsGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVN 77
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
 703-949 1.39e-08

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 56.97  E-value: 1.39e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  703 SHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRhhEAELVTAQLMGLLP-GLASAMKYLSE-MGYVHRGLAARRVLLSSG 780
Cdd:cd06605     59 PYIVGFYGAFYSEGDISICMEYMDGGSLDKILK--EVGRIPERILGKIAvAVVKGLIYLHEkHKIIHRDVKPSNILVNSR 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  781 LICKISGFGrgprdraeaVYTTMVRSsllwphmllllsaiptgpmvyiLAlppslpglfplvvpclsqpGSFLRCggsgr 860
Cdd:cd06605    137 GQVKLCDFG---------VSGQLVDS----------------------LA-------------------KTFVGT----- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  861 spALWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPY--WDMSGQ----DVIKAVEDGfrlPPPR----NCPSQLHR 930
Cdd:cd06605    162 --RSYMAPERISGGKYTVKSDIWSLGLSLVE-LATGRFPYppPNAKPSmmifELLSYIVDE---PPPLlpsgKFSPDFQD 235

                          250
                   ....*....|....*....
gi 1958775623  931 LMLECWQKDPGERPRFSQI 949
Cdd:cd06605    236 FVSQCLQKDPTERPSYKEL 254
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
 648-954 1.73e-08

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 56.80  E-value: 1.73e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLqLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd05086      3 QEIGNGWFGKVLLGEI-YTGTSVARVVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIPYLLVFEFCDL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRHHE------AELVTAQLMGLlpGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAEavyt 801
Cdd:cd05086     82 GDLKTYLANQQeklrgdSQIMLLQRMAC--EIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKE---- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 tmvrssllwphmllllSAIPTGPMVYIlalppslpglfplvvpclsqpgsflrcggsgrsPALWAAPETLQFGH------ 875
Cdd:cd05086    156 ----------------DYIETDDKKYA---------------------------------PLRWTAPELVTSFQdgllaa 186

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  876 -FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAV--EDGFRLPPPR-NCP--SQLHRLMLECWQKdPGERPRFSQI 949
Cdd:cd05086    187 eQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNHVikERQVKLFKPHlEQPysDRWYEVLQFCWLS-PEKRPTAEEV 265


                   ....*
gi 1958775623  950 HSILS 954
Cdd:cd05086    266 HRLLT 270
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
 700-949 2.03e-08

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 56.92  E-value: 2.03e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  700 FDHSHIVRLE--GVVTRGNP---LMIVTEYMNLGALDDFLRHHEAE---LVTAQLMGLLPGLASAMKYLSEM---GYVHR 768
Cdd:cd13986     54 FNHPNILRLLdsQIVKEAGGkkeVYLLLPYYKRGSLQDEIERRLVKgtfFPEDRILHIFLGICRGLKAMHEPelvPYAHR 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  769 GLAARRVLLSSGLICKISGFGRGPRDRAEAVYTTMVRssllwphmllllsaiptgpMVYILAlppslpglfplvvpclSQ 848
Cdd:cd13986    134 DIKPGNVLLSEDDEPILMDLGSMNPARIEIEGRREAL-------------------ALQDWA----------------AE 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 pgsflRCGGSGRSPALWAAP--ETLqfghfSSASDVWSFGIVMWEVMaFGERPYwDM---SGQDVIKAVEDG-FRLPPPR 922
Cdd:cd13986    179 -----HCTMPYRAPELFDVKshCTI-----DEKTDIWSLGCTLYALM-YGESPF-ERifqKGDSLALAVLSGnYSFPDNS 246

                          250       260
                   ....*....|....*....|....*..
gi 1958775623  923 NCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd13986    247 RYSEELHQLVKSMLVVNPAERPSIDDL 273
SAM_EPH-A1 cd09542
SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 988-1047 2.06e-08

SAM domain of EPH-A1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A1 subfamily of the receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A1 receptors and appears to mediate cell-cell initiated signal transduction. Activation of these receptors leads to inhibition of cell spreading and migration in a RhoA-ROCK-dependent manner. EPH-A1 receptors are known to bind ILK (integrin-linked kinase) which is the mediator of interactions between integrin and the actin cytoskeleton. However SAM is not sufficient for this interaction; it rather plays an ancillary role. SAM domains of Eph-A1 receptors do not form homo/hetero dimers/oligomers. EphA1 gene was found expressed widely in differentiated epithelial cells. In a number of different malignant tumors EphA1 genes are downregulated. In breast carcinoma the downregulation is associated with invasive behavior of the cell.


Pssm-ID: 188941  Cd Length: 63  Bit Score: 51.55  E-value: 2.06e-08
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  988 FGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09542      4 YRSVSEWLESIRMKRYILHFRSAGLDTMECVLELTAEDLTQMGITLPGHQKRILCSIQGF 63
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
 697-949 2.10e-08

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 56.71  E-value: 2.10e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA--ELVTAQlmgLLPGLASAMKYLSEMGYVHRGLAARR 774
Cdd:cd14098     55 LKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGGDLMDFIMAWGAipEQHARE---LTKQILEAMAYTHSMGITHRDLKPEN 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  775 VLLSSG--LICKISGFGRGPRDRAEAVYTTMVrssllwphmllllsaiptGPMVYIlalppslpglfplvvpclsqpgsf 852
Cdd:cd14098    132 ILITQDdpVIVKISDFGLAKVIHTGTFLVTFC------------------GTMAYL------------------------ 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  853 lrcggsgrSPALWAAPETLQFGHFSSASDVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDGFRLPPP---RNCPSQLH 929
Cdd:cd14098    170 --------APEILMSKEQNLQGGYSNLVDMWSVGCLVY-VMLTGALPFDGSSQLPVEKRIRKGRYTQPPlvdFNISEEAI 240

                          250       260
                   ....*....|....*....|
gi 1958775623  930 RLMLECWQKDPGERPRFSQI 949
Cdd:cd14098    241 DFILRLLDVDPEKRMTAAQA 260
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
 645-949 2.26e-08

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 56.19  E-value: 2.26e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFLA-EALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd14075      5 RIRGELGSGNFSQVKLGIHQLTKEK---VAIKILDKTKLDQKTQRLLSrEISSMEKLHHPNIIRLYEVVETLSKLHLVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGAL------DDFLRHHEAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdrae 797
Cdd:cd14075     82 YASGGELytkistEGKLSESEAKPLFAQIV-------SAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFG-------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 avyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvVPCLSQPGSFLR--CGgsgrSPAlWAAPETLQFGH 875
Cdd:cd14075    147 ---------------------------------------------FSTHAKRGETLNtfCG----SPP-YAAPELFKDEH 176

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  876 FSSAS-DVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDG-FRLPP--PRNCpSQLHRLMLecwQKDPGERPRFSQI 949
Cdd:cd14075    177 YIGIYvDIWALGVLLY-FMVTGVMPFRAETVAKLKKCILEGtYTIPSyvSEPC-QELIRGIL---QPVPSDRYSIDEI 249
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
 674-954 2.78e-08

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 56.47  E-value: 2.78e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  674 AVHTLREGCSDSQKLSFLaeaLTLgqfDHSHIVRLEGVVTRgnPLMIVTEYMNLGALDDFLRHHE---AELVTAQLMGLL 750
Cdd:cd14000     47 ATDAMKNFRLLRQELTVL---SHL---HHPSIVYLLGIGIH--PLMLVLELAPLGSLDHLLQQDSrsfASLGRTLQQRIA 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  751 PGLASAMKYLSEMGYVHRGLAARRVLL-----SSGLICKISGFGrgprdraeavyttmvrssllwphmllllsaiptgpm 825
Cdd:cd14000    119 LQVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIIIKIADYG------------------------------------ 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  826 vyilalppslpglfplvvpcLSQPGSFLRCGGSGRSPAlWAAPETLQFGH-FSSASDVWSFGIVMWEVMAFGERPYWDMS 904
Cdd:cd14000    163 --------------------ISRQCCRMGAKGSEGTPG-FRAPEIARGNViYNEKVDVFSFGMLLYEILSGGAPMVGHLK 221

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  905 GQDVIKAVEdgfRLPPP---RNC--PSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd14000    222 FPNEFDIHG---GLRPPlkqYECapWPEVEVLMKKCWKENPQQRPTAVTVVSILN 273
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
 640-944 2.94e-08

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 56.24  E-value: 2.94e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  640 DAKSVTLEKSLGAGRFGDLCCGCLQlpGRQelpVAVHTLR----EGCSDSqklSFLAEaLTLGQFDHSHIVRL---EGVV 712
Cdd:cd13979      1 DWEPLRLQEPLGSGGFGSVYKATYK--GET---VAVKIVRrrrkNRASRQ---SFWAE-LNAARLRHENIVRVlaaETGT 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  713 TRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgp 792
Cdd:cd13979     72 DFASLGLIIMEYCGNGTLQQLIYEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFG--- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  793 rdraeavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpCLSQPGSFlRCGGSGRSPA----LWAAP 868
Cdd:cd13979    149 ----------------------------------------------------CSVKLGEG-NEVGTPRSHIggtyTYRAP 175

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  869 ETLQFGHFSSASDVWSFGIVMWEvMAFGERPYwdmSG--QDVIKAV-EDGFRLPPPRNCPSQ----LHRLMLECWQKDPG 941
Cdd:cd13979    176 ELLKGERVTPKADIYSFGITLWQ-MLTRELPY---AGlrQHVLYAVvAKDLRPDLSGLEDSEfgqrLRSLISRCWSAQPA 251


                   ...
gi 1958775623  942 ERP 944
Cdd:cd13979    252 ERP 254
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
 693-949 3.62e-08

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 55.86  E-value: 3.62e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHH------EAELVTAQLMgllpglaSAMKYLSEMGYV 766
Cdd:cd14071     49 EVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEIFDYLAQHgrmsekEARKKFWQIL-------SAVEYCHKRHIV 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  767 HRGLAARRVLLSSGLICKISGFGRGprdraeavyttmvrssllwphmllllsaiptgpmvyilalppslpGLFplvvpcl 846
Cdd:cd14071    122 HRDLKAENLLLDANMNIKIADFGFS---------------------------------------------NFF------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  847 sQPGSFLR--CGgsgrSPAlWAAPETLQFGHFSSAS-DVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDG-FRLP--P 920
Cdd:cd14071    150 -KPGELLKtwCG----SPP-YAAPEVFEGKEYEGPQlDIWSLGVVLY-VLVCGALPFDGSTLQTLRDRVLSGrFRIPffM 222

                          250       260
                   ....*....|....*....|....*....
gi 1958775623  921 PRNCpSQLHRLMLecwQKDPGERPRFSQI 949
Cdd:cd14071    223 STDC-EHLIRRML---VLDPSKRLTIEQI 247
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
 864-956 4.42e-08

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 55.66  E-value: 4.42e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  864 LWAAPETLQFGHFSSASDVWSFGIVMWEVMAFGErPYWDMSGQDvikAVEDGFRLPPPRNC----PS-----------QL 928
Cdd:cd14044    166 LWTAPEHLRQAGTSQKGDVYSYGIIAQEIILRKE-TFYTAACSD---RKEKIYRVQNPKGMkpfrPDlnlesagererEV 241

                           90       100
                   ....*....|....*....|....*...
gi 1958775623  929 HRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14044    242 YGLVKNCWEEDPEKRPDFKKIENTLAKI 269
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
415-589 5.18e-08

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 56.93  E-value: 5.18e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  415 LRPGARYTVRVAALNG---VSGPAAAagatyaqVTVSTGPGAPWEEDEIRRDRVEPQSVSLSWrepvpAGASGTNRTEYE 491
Cdd:COG3401    292 LTNGTTYYYRVTAVDAagnESAPSNV-------VSVTTDLTPPAAPSGLTATAVGSSSITLSW-----TASSDADVTGYN 359

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  492 IryYEKGQSEQTYSTVKTGAPAV--TVTNLKPATRYVFQIRAASPGPSWEAQSFSPSIEVQTPGEVAPGSRDQSPAVVVT 569
Cdd:COG3401    360 V--YRSTSGGGTYTKIAETVTTTsyTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVDAVPLTD 437

                          170       180
                   ....*....|....*....|
gi 1958775623  570 VVTISALLVLGSVMSVLAIW 589
Cdd:COG3401    438 VAGATAAASAASNPGVSAAV 457
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
 673-954 5.41e-08

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 55.58  E-value: 5.41e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELV-----TAQLM 747
Cdd:cd14664     20 VAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGELLHSRPESQPpldweTRQRI 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  748 GLlpGLASAMKYLSE---MGYVHRGLAARRVLLSSGLICKISGFgrgprdraeavyttmvrssllwphmllllsaiptgp 824
Cdd:cd14664    100 AL--GSARGLAYLHHdcsPLIIHRDVKSNNILLDEEFEAHVADF------------------------------------ 141

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  825 mvyilalppslpGLFPLVVPCLSQPGSFLRcGGSGrspalWAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMS 904
Cdd:cd14664    142 ------------GLAKLMDDKDSHVMSSVA-GSYG-----YIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFDEAF 202

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  905 GQD----------------VIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd14664    203 LDDgvdivdwvrglleekkVEALVDPDLQGVYKLEEVEQVFQVALLCTQSSPMERPTMREVVRMLE 268
SAM_caskin1,2_repeat1 cd09497
SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 ...
 993-1048 5.68e-08

SAM domain of caskin protein repeat 1; SAM (sterile alpha motif) domain repeat 1 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and apparently may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188896  Cd Length: 66  Bit Score: 50.33  E-value: 5.68e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  993 AWLEALDLCRYKDNFSAAGYgSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQ 1048
Cdd:cd09497      9 DWLREFGLEEYTPNFIKAGY-DLPTISRMTPEDLTAIGITKPGHRKKLKSEIAQLQ 63
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
 617-973 6.35e-08

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 55.38  E-value: 6.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  617 RTFLDPqscGDPLQAVHLFAKeldaksvtleksLGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFlAEALT 696
Cdd:cd06659     11 RMVVDQ---GDPRQLLENYVK------------IGEGSTGVVCIAREKHSGRQ---VAVKMMDLRKQQRRELLF-NEVVI 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  697 LGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRhhEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVL 776
Cdd:cd06659     72 MRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTDIVS--QTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSIL 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  777 LSSGLICKISGFGrgprdraeavyttmvrssllwphmllllsaiptgpmvYILALPPSLPGLFPLVvpclsqpgsflrcg 856
Cdd:cd06659    150 LTLDGRVKLSDFG-------------------------------------FCAQISKDVPKRKSLV-------------- 178

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  857 gsgrSPALWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGfrlPPP--RNC--PSQLHRLM 932
Cdd:cd06659    179 ----GTPYWMAPEVISRCPYGTEVDIWSLGIMVIE-MVDGEPPYFSDSPVQAMKRLRDS---PPPklKNShkASPVLRDF 250

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1958775623  933 LE-CWQKDPGERprfsqihSILSKMGQEPEPSKCASTTCLRP 973
Cdd:cd06659    251 LErMLVRDPQER-------ATAQELLDHPFLLQTGLPECLVP 285
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
 642-944 6.86e-08

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 54.94  E-value: 6.86e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  642 KSVTLEKSLGAGRFGDLCCGCLQLPGRqelPVAVHT--LREGCSD----SQKLSFLAealtlgQFDHSHIVRLEGVVTRG 715
Cdd:cd06609      1 ELFTLLERIGKGSFGEVYKGIDKRTNQ---VVAIKVidLEEAEDEiediQQEIQFLS------QCDSPYITKYYGSFLKG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  716 NPLMIVTEYMNLGALDDFLRHHE-AELVTAQLM-GLLPGLasamKYLSEMGYVHRGLAARRVLLSS-GLIcKISGFGrgp 792
Cdd:cd06609     72 SKLWIIMEYCGGGSVLDLLKPGPlDETYIAFILrEVLLGL----EYLHSEGKIHRDIKAANILLSEeGDV-KLADFG--- 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  793 rdraeaVYTTMVRSSllwphmllllsaiptgpmvyilalppslpglfplvvpclSQPGSFLrcggsGrSPaLWAAPETLQ 872
Cdd:cd06609    144 ------VSGQLTSTM---------------------------------------SKRNTFV-----G-TP-FWMAPEVIK 171

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  873 FGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIkavedgFRLP---PP---RNCPSQLHRLMLE-CWQKDPGERP 944
Cdd:cd06609    172 QSGYDEKADIWSLGITAIE-LAKGEPPLSDLHPMRVL------FLIPknnPPsleGNKFSKPFKDFVElCLNKDPKERP 243
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
 650-944 7.34e-08

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 55.06  E-value: 7.34e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGclqLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd06642     12 IGKGSFGEVYKG---IDNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGS 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRhhEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdRAEAVYTTMVRSSLl 809
Cdd:cd06642     89 ALDLLK--PGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFG-----VAGQLTDTQIKRNT- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvyILALPpslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd06642    161 ------------------FVGTP-------------------------------FWMAPEVIKQSAYDFKADIWSLGITA 191

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  890 WEvMAFGERPYWDMSGQDVIKAVedgfrlppPRNCPSQLH--------RLMLECWQKDPGERP 944
Cdd:cd06642    192 IE-LAKGEPPNSDLHPMRVLFLI--------PKNSPPTLEgqhskpfkEFVEACLNKDPRFRP 245
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
 648-943 9.76e-08

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 54.37  E-value: 9.76e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFlAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNL 727
Cdd:cd06648     13 VKIGEGSTGIVCIATDKSTGRQ---VAVKKMDLRKQQRRELLF-NEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEG 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  728 GALDDFLRH---HEAELVTAQLMGLlpglaSAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmv 804
Cdd:cd06648     89 GALTDIVTHtrmNEEQIATVCRAVL-----KALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFG--------------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  805 rssllwphmllllsaiptgpmvYILALPPSLPGLFPLVvpclsqpgsflrcggsgrSPALWAAPETLQFGHFSSASDVWS 884
Cdd:cd06648    149 ----------------------FCAQVSKEVPRRKSLV------------------GTPYWMAPEVISRLPYGTEVDIWS 188

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  885 FGIVMWEvMAFGERPYWDMSGQDVIKAVEDgfrLPPPR-----NCPSQLHRLMLECWQKDPGER 943
Cdd:cd06648    189 LGIMVIE-MVDGEPPYFNEPPLQAMKRIRD---NEPPKlknlhKVSPRLRSFLDRMLVRDPAQR 248
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
 696-949 9.82e-08

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 54.29  E-value: 9.82e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  696 TLGQFDHSHIVRLEG--VVTRGNP----LMIVTEYMNLGALDDFLRHHEAeLVTAQLMGLLPGLASAMKYLSEMGYVHRG 769
Cdd:cd14012     51 SLKKLRHPNLVSYLAfsIERRGRSdgwkVYLLTEYAPGGSLSELLDSVGS-VPLDTARRWTLQLLEALEYLHRNGVVHKS 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  770 LAARRVLLSSGL---ICKISGFGRGPRDRaeavyttmvrssllwphmllllSAIPTGPMVYIlalppslpglfplvvpcl 846
Cdd:cd14012    130 LHAGNVLLDRDAgtgIVKLTDYSLGKTLL----------------------DMCSRGSLDEF------------------ 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  847 sqpgsflrcggsgrSPALWAAPETLQFGH-FSSASDVWSFGIVMWEVmafgerpywdMSGQDVIKAVEDGFRLPPPRNCP 925
Cdd:cd14012    170 --------------KQTYWLPPELAQGSKsPTRKTDVWDLGLLFLQM----------LFGLDVLEKYTSPNPVLVSLDLS 225

                          250       260
                   ....*....|....*....|....
gi 1958775623  926 SQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14012    226 ASLQDFLSKCLSLDPKKRPTALEL 249
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
 680-903 9.92e-08

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. The STRAD alpha subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 55.33  E-value: 9.92e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  680 EGCSDsQKLSFLAEALTLGQ-FDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHH----EAELVTAQLmglLPGLA 754
Cdd:cd08227     36 EACTN-EMVTFLQGELHVSKlFNHPNIVPYRATFIADNELWVVTSFMAYGSAKDLICTHfmdgMSELAIAYI---LQGVL 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  755 SAMKYLSEMGYVHRGLAARRVLLSsglickISGfgrgprdraeAVYTTMVRSSLLWPHMLLLLSAIPTGPMVYILALPps 834
Cdd:cd08227    112 KALDYIHHMGYVHRSVKASHILIS------VDG----------KVYLSGLRSNLSMINHGQRLRVVHDFPKYSVKVLP-- 173

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  835 lpglfplvvpclsqpgsflrcggsgrspalWAAPETLQ--FGHFSSASDVWSFGIVMWEvMAFGERPYWDM 903
Cdd:cd08227    174 ------------------------------WLSPEVLQqnLQGYDAKSDIYSVGITACE-LANGHVPFKDM 213
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 693-955 1.41e-07

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 53.81  E-value: 1.41e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFL-RHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLA 771
Cdd:cd08225     49 EVILLAKMKHPNIVTFFASFQENGRLFIVMEYCDGGDLMKRInRQRGVLFSEDQILSWFVQISLGLKHIHDRKILHRDIK 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  772 ARRVLLSS-GLICKISGFG--RGPRDRAEAVYTtmvrssllwphmllllsaiptgpmvyilalppslpglfplvvpCLSQ 848
Cdd:cd08225    129 SQNIFLSKnGMVAKLGDFGiaRQLNDSMELAYT-------------------------------------------CVGT 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  849 PgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSFGIVMWEVMAFgERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQL 928
Cdd:cd08225    166 P--------------YYLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDL 230

                          250       260
                   ....*....|....*....|....*..
gi 1958775623  929 HRLMLECWQKDPGERPrfsQIHSILSK 955
Cdd:cd08225    231 RSLISQLFKVSPRDRP---SITSILKR 254
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
 680-974 1.68e-07

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. The STRAD-beta subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 54.49  E-value: 1.68e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  680 EGCSDsQKLSFLAEALTLGQ-FDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMG-LLPGLASAM 757
Cdd:cd08226     36 DNCSE-EHLKALQNEVVLSHfFRHPNIMTHWTVFTEGSWLWVISPFMAYGSARGLLKTYFPEGMNEALIGnILYGAIKAL 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  758 KYLSEMGYVHRGLAARRVLLSSGLICKISGFGRgprdraeavYTTMVRSSLLWPhmllllsaiptgpMVYilalppSLPG 837
Cdd:cd08226    115 NYLHQNGCIHRSVKASHILISGDGLVSLSGLSH---------LYSMVTNGQRSK-------------VVY------DFPQ 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  838 LFPLVVPclsqpgsflrcggsgrspalWAAPETLQ--FGHFSSASDVWSFGIVMWEvMAFGERPYWDM------------ 903
Cdd:cd08226    167 FSTSVLP--------------------WLSPELLRqdLHGYNVKSDIYSVGITACE-LARGQVPFQDMrrtqmllqklkg 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  904 ----------------------SGQD------VIKA------VEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd08226    226 ppyspldifpfpelesrmknsqSGMDsgigesVATSsmtrtmTSERLQTPSSKTFSPAFHNLVELCLQQDPEKRPSASSL 305

                          330       340
                   ....*....|....*....|....*..
gi 1958775623  950 --HSILSKMGQEPEpskcASTTCLRPP 974
Cdd:cd08226    306 lsHSFFKQVKEQTQ----ASLLSLLPP 328
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
 650-949 2.50e-07

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 53.31  E-value: 2.50e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALT-----LGQFDHSHIVRLEGVVTRGNPLMIVTEY 724
Cdd:cd06628      8 IGSGSFGSVYLGMNASSGELMAVKQVELPSVSAENKDRKKSMLDALQreialLRELQHENIVQYLGSSSDANHLNIFLEY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  725 MNLGALDDFLRHH---EAELVTAQLMGLLPGLasamKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRDRAEAVYT 801
Cdd:cd06628     88 VPGGSVATLLNNYgafEESLVRNFVRQILKGL----NYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLST 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  802 TMVRSSllwphmllllsaiptgpmvyilalpPSLPGlfplvvpclsqpgsflrcggsgrsPALWAAPETLQFGHFSSASD 881
Cdd:cd06628    164 KNNGAR-------------------------PSLQG------------------------SVFWMAPEVVKQTSYTRKAD 194

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  882 VWSFGIVMWEVMAfGERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd06628    195 IWSLGCLVVEMLT-GTHPFPDCTQMQAIFKIGENASPTIPSNISSEARDFLEKTFEIDHNKRPTADEL 261
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
 646-949 2.70e-07

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 53.54  E-value: 2.70e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKsLGAGRFGDLCCGclqLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd06641      9 LEK-IGKGSFGEVFKG---IDNRTQKVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEYL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRhhEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRgprdrAEAVYTTMVR 805
Cdd:cd06641     85 GGGSALDLLE--PGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGV-----AGQLTDTQIK 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  806 SSLlwphmllllsaiptgpmvyILALPpslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDVWSF 885
Cdd:cd06641    158 RN*-------------------FVGTP-------------------------------FWMAPEVIKQSAYDSKADIWSL 187

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  886 GIVMWEvMAFGERPYWDMSGQDVIkavedgFRLP---PPR---NCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd06641    188 GITAIE-LARGEPPHSELHPMKVL------FLIPknnPPTlegNYSKPLKEFVEACLNKEPSFRPTAKEL 250
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 651-948 2.93e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 53.08  E-value: 2.93e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  651 GAGRFG------DLCCGCLqlpgrqelpVAVHTLREGCSDSQKLSFLAEALT-LGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd06626      9 GEGTFGkvytavNLDTGEL---------MAMKEIRFQDNDPKTIKEIADEMKvLEGLDHPNLVRYYGVEVHREEVYIFME 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRH--HEAELV----TAQlmgLLPGLAsamkYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdrae 797
Cdd:cd06626     80 YCQEGTLEELLRHgrILDEAVirvyTLQ---LLEGLA----YLHENGIVHRDIKPANIFLDSNGLIKLGDFG-------- 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 avyttmvrssllwphmllllSAIptgpmvyILALPpslpglfplvvpclSQPGSFLRCGGSGRSPAlWAAPE----TLQF 873
Cdd:cd06626    145 --------------------SAV-------KLKNN--------------TTTMAPGEVNSLVGTPA-YMAPEvitgNKGE 182

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  874 GHFsSASDVWSFGIVMWEvMAFGERPYWDMSGQ-DVIKAVEDGFRLP-PPRNCPSQLHRLMLE-CWQKDPGERPRFSQ 948
Cdd:cd06626    183 GHG-RAADIWSLGCVVLE-MATGKRPWSELDNEwAIMYHVGMGHKPPiPDSLQLSPEGKDFLSrCLESDPKKRPTASE 258
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
 699-956 3.07e-07

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 52.94  E-value: 3.07e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  699 QFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLS 778
Cdd:cd14045     58 ELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNEDIPLNWGFRFSFATDIARGMAYLHQHKIYHGRLKSSNCVID 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  779 SGLICKISGFGrgprdraeavyTTMVRSsllwphmllllsaiptgpmvyilalppslpglfplvvpclsQPGSFLRCGGS 858
Cdd:cd14045    138 DRWVCKIADYG-----------LTTYRK-----------------------------------------EDGSENASGYQ 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  859 GRSPALWAAPE--TLQFGHFSSASDVWSFGIVMWEVMAFGErPYwdmsgQDVIKAVEDGFRLPPPR----------NCPS 926
Cdd:cd14045    166 QRLMQVYLPPEnhSNTDTEPTQATDVYSYAIILLEIATRND-PV-----PEDDYSLDEAWCPPLPElisgktenscPCPA 239

                          250       260       270
                   ....*....|....*....|....*....|
gi 1958775623  927 QLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14045    240 DYVELIRRCRKNNPAQRPTFEQIKKTLHKI 269
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
 673-943 4.77e-07

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 52.30  E-value: 4.77e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHtlregCSD-SQKLSFLAEALTLGQFDHSHIVRL-EGVVTRgNPLMIVTEYMNLGALDDFLRHHEAeLVTAQLMGLL 750
Cdd:cd14010     28 VAIK-----CVDkSKRPEVLNEVRLTHELKHPNVLKFyEWYETS-NHLWLVVEYCTGGDLETLLRQDGN-LPESSVRKFG 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  751 PGLASAMKYLSEMGYVHRGLAARRVLL-SSGLIcKISGFGrgprdraeavyttmvrssllwphmllllsaiptgpmvyiL 829
Cdd:cd14010    101 RDLVRGLHYIHSKGIIYCDLKPSNILLdGNGTL-KLSDFG---------------------------------------L 140

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  830 A--LPPSLPGLFPLVVPCLSQPGSFLRCGGSGrSPaLWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQD 907
Cdd:cd14010    141 ArrEGEILKELFGQFSDEGNVNKVSKKQAKRG-TP-YYMAPELFQGGVHSFASDLWALGCVLYE-MFTGKPPFVAESFTE 217

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1958775623  908 VI-KAVEDGFRLPPPR---NCPSQLHRLMLECWQKDPGER 943
Cdd:cd14010    218 LVeKILNEDPPPPPPKvssKPSPDFKSLLKGLLEKDPAKR 257
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
 718-944 6.73e-07

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 52.27  E-value: 6.73e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYL-SE-MGY------VHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd14056     68 LWLITEYHEHGSLYDYLQRNT--LDTEEALRLAYSAASGLAHLhTEiVGTqgkpaiAHRDLKSKNILVKRDGTCCIADLG 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  790 ---RGPRDRAeavyttmvrssllwphmllllsaiptgpmvyILALPPSLpglfplvvpclsqpgsflRCGgSGRspalWA 866
Cdd:cd14056    146 lavRYDSDTN-------------------------------TIDIPPNP------------------RVG-TKR----YM 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APE----TLQFGHFSS--ASDVWSFGIVMWEVMAFGER---------PYWDMSGQD--------VIkaVEDGFRLPPP-- 921
Cdd:cd14056    172 APEvlddSINPKSFESfkMADIYSFGLVLWEIARRCEIggiaeeyqlPYFGMVPSDpsfeemrkVV--CVEKLRPPIPnr 249

                          250       260
                   ....*....|....*....|....*.
gi 1958775623  922 -RNCP--SQLHRLMLECWQKDPGERP 944
Cdd:cd14056    250 wKSDPvlRSMVKLMQECWSENPHARL 275
SAM_AIDA1AB-like_repeat1 cd09499
SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
 990-1047 6.90e-07

SAM domain of AIDA1AB-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM1 domain has a potential phosphorylation site for CMGC group of serine/threonine kinases. SAM domains of the AIDA1-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188898  Cd Length: 67  Bit Score: 47.29  E-value: 6.90e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTE--MTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09499      4 SVGQWLESIGLPQYESKLLLNGFDDVDFLGSgvMEDQDLKEIGITDEQHRQIILQAARSL 63
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
 867-950 7.59e-07

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 52.06  E-value: 7.59e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWD-----------MSGQDVIKAV--EDGFRLPPPRNCPSQLHRLML 933
Cdd:cd06620    171 SPERIQGGKYSVKSDVWSLGLSIIE-LALGEFPFAGsnddddgyngpMGILDLLQRIvnEPPPRLPKDRIFPKDLRDFVD 249

                           90
                   ....*....|....*..
gi 1958775623  934 ECWQKDPGERPRFSQIH 950
Cdd:cd06620    250 RCLLKDPRERPSPQLLL 266
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
 990-1044 7.60e-07

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886 [Multi-domain]  Cd Length: 56  Bit Score: 46.85  E-value: 7.60e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  990 SVGAWLEALDLCRYKDNFsAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGI 1044
Cdd:cd09487      1 DVAEWLESLGLEQYADLF-RKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAI 54
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 648-951 8.94e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 51.51  E-value: 8.94e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  648 KSLGAGRFGDLCCGCLQLPGRQ------ELPVAVHTLRegcsDSQKlsflaEALTLGQFDHSHIVRLEGVVTRGNPLMIV 721
Cdd:cd08219      6 RVVGEGSFGRALLVQHVNSDQKyamkeiRLPKSSSAVE----DSRK-----EAVLLAKMKHPNIVAFKESFEADGHLYIV 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  722 TEYMNLGALDDFLRHHEAELVTAQ-LMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavy 800
Cdd:cd08219     77 MEYCDGGDLMQKIKLQRGKLFPEDtILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFG----------- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  801 ttmvrssllwphmlllLSAIPTGPMVYILALPPSlpglfPLVVPclsqpgsflrcggsgrsPALWaapETLQFghfSSAS 880
Cdd:cd08219    146 ----------------SARLLTSPGAYACTYVGT-----PYYVP-----------------PEIW---ENMPY---NNKS 181

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  881 DVWSFGIVMWEVMAFgERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd08219    182 DIWSLGCILYELCTL-KHPFQANSWKNLILKVCQGSYKPLPSHYSYELRSLIKQMFKRNPRSRPSATTILS 251
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
 693-954 1.16e-06

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 51.11  E-value: 1.16e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRgnPLMIVTEYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAA 772
Cdd:cd14068     37 ELVVLSHLHHPSLVALLAAGTA--PRMLVMELAPKGSLDALLQQDNASLTRTLQHRIALHVADGLRYLHSAMIIYRDLKP 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  773 RRVLL-----SSGLICKISGFGRgprdrAEAVYTTMVRSSllwphmllllsaiptgpmvyilalppslpglfplvvpcls 847
Cdd:cd14068    115 HNVLLftlypNCAIIAKIADYGI-----AQYCCRMGIKTS---------------------------------------- 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  848 qpgsflrCGGSGrspalWAAPETLQfGH--FSSASDVWSFGIVMWEVMAFGERPYWDMSGQDVIKAVEDGFRLPPP---R 922
Cdd:cd14068    150 -------EGTPG-----FRAPEVAR-GNviYNQQADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPvkeY 216

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1958775623  923 NCP--SQLHRLMLECWQKDPGERPRFSQIHSILS 954
Cdd:cd14068    217 GCApwPGVEALIKDCLKENPQCRPTSAQVFDILN 250
fn3 pfam00041
Fibronectin type III domain;
339-431 1.51e-06

Fibronectin type III domain;


Pssm-ID: 394996 [Multi-domain]  Cd Length: 85  Bit Score: 47.02  E-value: 1.51e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  339 SAPRDLQYSlSRSPLALRLRWLPPEDSGGrSDVTYSLLCLRCGRDGPagacqpcgPRVAFVPRQaglrERAATLLHLRPG 418
Cdd:pfam00041    1 SAPSNLTVT-DVTSTSLTVSWTPPPDGNG-PITGYEVEYRPKNSGEP--------WNEITVPGT----TTSVTLTGLKPG 66

                           90
                   ....*....|...
gi 1958775623  419 ARYTVRVAALNGV 431
Cdd:pfam00041   67 TEYEVRVQAVNGG 79
FN3 COG3401
Fibronectin type 3 domain [General function prediction only];
417-531 1.65e-06

Fibronectin type 3 domain [General function prediction only];


Pssm-ID: 442628 [Multi-domain]  Cd Length: 603  Bit Score: 51.93  E-value: 1.65e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  417 PGARYTVRVAALNgvSGPAAAAGATYAQVTVSTGPGAPweeDEIRRDRVEPQSVSLSWREPVPAGASGtnrteYEIryYE 496
Cdd:COG3401    201 PGTTYYYRVAATD--TGGESAPSNEVSVTTPTTPPSAP---TGLTATADTPGSVTLSWDPVTESDATG-----YRV--YR 268

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1958775623  497 KGQSEQTYSTVKTGAPAV-TVTNLKPATRYVFQIRA 531
Cdd:COG3401    269 SNSGDGPFTKVATVTTTSyTDTGLTNGTTYYYRVTA 304
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
 644-956 1.86e-06

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 50.74  E-value: 1.86e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCcgclqlPGRQELPVAVHTLREGCSDSQKLS-FLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:cd14152      2 IELGELIGQGRWGKVH------RGRWHGEVAIRLLEIDGNNQDHLKlFKKEVMNYRQTRHENVVLFMGACMHPPHLAIIT 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICkISGFGrgprdraeavytT 802
Cdd:cd14152     76 SFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFG------------L 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSSLLWPHMLLLLSAIPTGPMVYilalppslpgLFPLVVPCLSqPGSflrcgGSGRSPalwaapetlqfghFSSASDV 882
Cdd:cd14152    143 FGISGVVQEGRRENELKLPHDWLCY----------LAPEIVREMT-PGK-----DEDCLP-------------FSKAADV 193

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  883 WSFGIVMWEVMAfGERPYWDMSGQDVIKAVEDG---FRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14152    194 YAFGTIWYELQA-RDWPLKNQPAEALIWQIGSGegmKQVLTTISLGKEVTEILSACWAFDLEERPSFTLLMDMLEKL 269
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
 646-789 1.93e-06

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 50.60  E-value: 1.93e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGDLCCGCLQLPGRQelpVAVHTL-REGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEY 724
Cdd:cd14072      4 LLKTIGKGNFAKVKLARHVLTGRE---VAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEY 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  725 MNLGALDDFLRHH------EAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd14072     81 ASGGEVFDYLVAHgrmkekEARAKFRQIV-------SAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFG 144
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
 701-804 3.29e-06

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 50.02  E-value: 3.29e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  701 DHSHIVRLEGVVTRGNPLMIVTEYMnLGALDDFLRHHEAELVTAQ----LMGLLPGLAsamkYLSEMGYVHRGLAARRVL 776
Cdd:cd07832     58 GHPYVVKLRDVFPHGTGFVLVFEYM-LSSLSEVLRDEERPLTEAQvkryMRMLLKGVA----YMHANRIMHRDLKPANLL 132

                           90       100       110
                   ....*....|....*....|....*....|
gi 1958775623  777 LSSGLICKISGFG--RGPRDRAEAVYTTMV 804
Cdd:cd07832    133 ISSTGVLKIADFGlaRLFSEEDPRLYSHQV 162
FN3 cd00063
Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein ...
 338-434 3.96e-06

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.


Pssm-ID: 238020 [Multi-domain]  Cd Length: 93  Bit Score: 46.34  E-value: 3.96e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  338 PSAPRDLQYSlSRSPLALRLRWLPPEDSGGRSDvTYSLLClrcgRDGPAGACQPCGPRVAfvprqaglRERAATLLHLRP 417
Cdd:cd00063      1 PSPPTNLRVT-DVTSTSVTLSWTPPEDDGGPIT-GYVVEY----REKGSGDWKEVEVTPG--------SETSYTLTGLKP 66

                           90
                   ....*....|....*....
gi 1958775623  418 GARYTVRVAALN--GVSGP 434
Cdd:cd00063     67 GTEYEFRVRAVNggGESPP 85
FN3 smart00060
Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, ...
 338-431 5.04e-06

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.


Pssm-ID: 214495 [Multi-domain]  Cd Length: 83  Bit Score: 45.68  E-value: 5.04e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623   338 PSAPRDLQYSlSRSPLALRLRWLPPEDSGGRSDVTYsllCLRCGRDGpagacqpcGPRVAFVPRQAglRERAATLLHLRP 417
Cdd:smart00060    1 PSPPSNLRVT-DVTSTSVTLSWEPPPDDGITGYIVG---YRVEYREE--------GSEWKEVNVTP--SSTSYTLTGLKP 66

                            90
                    ....*....|....
gi 1958775623   418 GARYTVRVAALNGV 431
Cdd:smart00060   67 GTEYEFRVRAVNGA 80
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 650-943 5.66e-06

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 49.26  E-value: 5.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCcgcLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd14167     11 LGTGAFSEVV---LAEEKRTQKLVAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGGE 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDD------FLRHHEAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRVL---LSSGLICKISGFGRGPRDRAEAVY 800
Cdd:cd14167     88 LFDrivekgFYTERDASKLIFQIL-------DAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKIEGSGSVM 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  801 TTMvrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrCGGSGrspalWAAPETLQFGHFSSAS 880
Cdd:cd14167    161 STA---------------------------------------------------CGTPG-----YVAPEVLAQKPYSKAV 184

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  881 DVWSFGIVMWeVMAFGERPYWDMSG----QDVIKAvEDGFRLPPPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd14167    185 DCWSIGVIAY-ILLCGYPPFYDENDaklfEQILKA-EYEFDSPYWDDISDSAKDFIQHLMEKDPEKR 249
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
 650-956 6.03e-06

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 49.24  E-value: 6.03e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLccgclqLPGRQELPVAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLG 728
Cdd:cd14153      8 IGKGRFGQV------YHGRWHGEVAIRLIDiERDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  729 ALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICkISGFGrgprdraeaVYTTmvrSSL 808
Cdd:cd14153     82 TLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFG---------LFTI---SGV 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  809 LWPHMLLLLSAIPTGPMVYilalppslpgLFPLVVPCLSqpgsflrcggsgrspalwaaPETLQFG-HFSSASDVWSFGI 887
Cdd:cd14153    149 LQAGRREDKLRIQSGWLCH----------LAPEIIRQLS--------------------PETEEDKlPFSKHSDVFAFGT 198

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  888 VMWEVMAfGERPYWDMSGQDVIKAVEDGFRLPPPR-NCPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14153    199 IWYELHA-REWPFKTQPAEAIIWQVGSGMKPNLSQiGMGKEISDILLFCWAYEQEERPTFSKLMEMLEKL 267
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
 989-1055 7.31e-06

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 44.59  E-value: 7.31e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  989 GSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGIsalqTRVLQLQ 1055
Cdd:cd09498      8 NDLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWEDLQDIGITKLGHQKKLMLAI----KKLKDLQ 70
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 678-953 7.54e-06

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 48.83  E-value: 7.54e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  678 LREGCSDSQKLsfLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFL--RHHEAELVTAQLMGLLPGLAS 755
Cdd:cd13996     41 LTEKSSASEKV--LREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLRDWIdrRNSSSKNDRKLALELFKQILK 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  756 AMKYLSEMGYVHRGLAARRVLLSSG-LICKISGFGrgprdRAEAVYTTMVRSSLLWPHMLLLLSAIPTGpmvyilalpps 834
Cdd:cd13996    119 GVSYIHSKGIVHRDLKPSNIFLDNDdLQVKIGDFG-----LATSIGNQKRELNNLNNNNNGNTSNNSVG----------- 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  835 lpglfplvvpclsqpgsflrcGGSgrspALWAAPETLQFGHFSSASDVWSFGIVMWEVM-AFGERpywdMSGQDVIKAVE 913
Cdd:cd13996    183 ---------------------IGT----PLYASPEQLDGENYNEKADIYSLGIILFEMLhPFKTA----MERSTILTDLR 233

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1958775623  914 DGfRLPP----PRNCPSQLHRLMLecwQKDPGERPRFSQIHSIL 953
Cdd:cd13996    234 NG-ILPEsfkaKHPKEADLIQSLL---SKNPEERPSAEQLLRSL 273
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
 641-956 9.24e-06

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 48.98  E-value: 9.24e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  641 AKSVTLEKSLGAGRFGDLCCGCLQlpgrqELPVAVHTLREgcSDSQKLSFLAEALTLGQFDHSHIVRLEGV-VTRGNP-- 717
Cdd:cd14142      4 ARQITLVECIGKGRYGEVWRGQWQ-----GESVAVKIFSS--RDEKSWFRETEIYNTVLLRHENILGFIASdMTSRNSct 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 -LMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYL--------SEMGYVHRGLAARRVLLSSGLICKISGF 788
Cdd:cd14142     77 qLWLITHYHENGSLYDYLQRTT--LDHQEMLRLALSAASGLVHLhteifgtqGKPAIAHRDLKSKNILVKSNGQCCIADL 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  789 GRgprdraeAVYTTMVRSSLLwphmllllsaIPTGPMVyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAP 868
Cdd:cd14142    155 GL-------AVTHSQETNQLD----------VGNNPRV------------------------------GTKRYMAPEVLD 187

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  869 ETLQFGHFSS--ASDVWSFGIVMWEV---MAFG------ERPYWDM-----SGQDVIKAV-EDGFRLPPPRNCPSQ---- 927
Cdd:cd14142    188 ETINTDCFESykRVDIYAFGLVLWEVarrCVSGgiveeyKPPFYDVvpsdpSFEDMRKVVcVDQQRPNIPNRWSSDptlt 267

                          330       340       350
                   ....*....|....*....|....*....|
gi 1958775623  928 -LHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14142    268 aMAKLMKECWYQNPSARLTALRIKKTLLKI 297
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
 650-949 1.05e-05

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 48.20  E-value: 1.05e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGclqLPGRQEL----PVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd06631      9 LGKGAYGTVYCG---LTSTGQLiavkQVELDTSDKEKAEKEYEKLQEEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEFV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRHHEA--ELV----TAQLmglLPGLAsamkYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGPRdraeav 799
Cdd:cd06631     86 PGGSIASILARFGAleEPVfcryTKQI---LEGVA----YLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKR------ 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  800 yttmvrssllwphmllllsaiptgpmvyilalppslpglfplvVPCLSQPGSFLRCGGSGRSPALWAAPETLQFGHFSSA 879
Cdd:cd06631    153 -------------------------------------------LCINLSSGSQSQLLKSMRGTPYWMAPEVINETGHGRK 189

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  880 SDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGFRLPP--PRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd06631    190 SDIWSIGCTVFE-MATGKPPWADMNPMAAIFAIGSGRKPVPrlPDKFSPEARDFVHACLTRDQDERPSAEQL 260
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
 650-789 1.11e-05

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 48.48  E-value: 1.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLccgcLQLPGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd06643     13 LGDGAFGKV----YKAQNKETGILAAAKVIDTKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGA 88

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd06643     89 VDAVMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFG 148
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
 868-949 1.12e-05

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 48.57  E-value: 1.12e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  868 PETLQfGHFSSASDVWSFGIVMWEvMAFGERPY--WDMSGQDVIKAVEDgfrlPPPRnCPS-----QLHRLMLECWQKDP 940
Cdd:cd06617    177 PELNQ-KGYDVKSDVWSLGITMIE-LATGRFPYdsWKTPFQQLKQVVEE----PSPQ-LPAekfspEFQDFVNKCLKKNY 249


                   ....*....
gi 1958775623  941 GERPRFSQI 949
Cdd:cd06617    250 KERPNYPEL 258
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 865-949 1.34e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 48.86  E-value: 1.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAFgERPYWDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERP 944
Cdd:PTZ00267   237 YLAPELWERKRYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFPCPVSSGMKALLDPLLSKNPALRP 315


                   ....*
gi 1958775623  945 RFSQI 949
Cdd:PTZ00267   316 TTQQL 320
PTKc_Wee1a cd14138
Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the ...
 646-778 1.35e-05

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271040 [Multi-domain]  Cd Length: 276  Bit Score: 48.10  E-value: 1.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKsLGAGRFGDL--CC----GCLQLPGRQELPVAvhtlreGCSDSQK-LSFLAEALTLGQfdHSHIVRLEGVVTRGNPL 718
Cdd:cd14138     10 LEK-IGSGEFGSVfkCVkrldGCIYAIKRSKKPLA------GSVDEQNaLREVYAHAVLGQ--HSHVVRYYSAWAEDDHM 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  719 MIVTEYMNLGALDDFLRHHEAE---LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLS 778
Cdd:cd14138     81 LIQNEYCNGGSLADAISENYRImsyFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFIS 143
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
 650-957 1.52e-05

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 48.10  E-value: 1.52e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFlAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGA 729
Cdd:cd06657     28 IGEGSTGIVCIATVKSSGKL---VAVKKMDLRKQQRRELLF-NEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGA 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  730 LDDFLRHheAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrssll 809
Cdd:cd06657    104 LTDIVTH--TRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFG-------------------- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  810 wphmllllsaiptgpmvYILALPPSLPGLFPLVvpclsqpgsflrcggsgrSPALWAAPETLQFGHFSSASDVWSFGIVM 889
Cdd:cd06657    162 -----------------FCAQVSKEVPRRKSLV------------------GTPYWMAPELISRLPYGPEVDIWSLGIMV 206

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  890 WEvMAFGERPYWDMSGQDVIKAVEDGfrLPPP-----RNCPSQ---LHRLMLecwqKDPGERPRFSQI--HSILSKMG 957
Cdd:cd06657    207 IE-MVDGEPPYFNEPPLKAMKMIRDN--LPPKlknlhKVSPSLkgfLDRLLV----RDPAQRATAAELlkHPFLAKAG 277
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
 646-951 1.59e-05

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 47.63  E-value: 1.59e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRfgdlcCGCLQLpgrqelpvAVHTL-----------REGCS-DSQKLSFLAEALTLGQFDHSHIVRLEGVVT 713
Cdd:cd14081      5 LGKTLGKGQ-----TGLVKL--------AKHCVtgqkvaikivnKEKLSkESVLMKVEREIAIMKLIEHPNVLKLYDVYE 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  714 RGNPLMIVTEYMNLGALDDFLRHHeAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGrgpr 793
Cdd:cd14081     72 NKKYLYLVLEYVSGGELFDYLVKK-GRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFG---- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  794 draeavyttMVRssllwphmllllsaiptgpmvyilalppslpglfplvvpcLSQPGSFLR--CGgsgrSPAlWAAPETL 871
Cdd:cd14081    147 ---------MAS----------------------------------------LQPEGSLLEtsCG----SPH-YACPEVI 172

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  872 QFGHF-SSASDVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDG-FRLPP--PRNCPSQLHRlMLEcwqKDPGERPRFS 947
Cdd:cd14081    173 KGEKYdGRKADIWSCGVILY-ALLVGALPFDDDNLRQLLEKVKRGvFHIPHfiSPDAQDLLRR-MLE---VNPEKRITIE 247


                   ....
gi 1958775623  948 QIHS 951
Cdd:cd14081    248 EIKK 251
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
 653-789 1.68e-05

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 48.09  E-value: 1.68e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  653 GRFGdlccgCLQLPGRQELPVAVHTLREgcsdSQKLSFLAEA--LTLGQFDHSHIVRLEGVVTRGNPLM----IVTEYMN 726
Cdd:cd14053      6 GRFG-----AVWKAQYLNRLVAVKIFPL----QEKQSWLTEReiYSLPGMKHENILQFIGAEKHGESLEaeywLITEFHE 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  727 LGALDDFLRHHEAELvtAQLMGLLPGLASAMKYL-SEMGY---------VHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd14053     77 RGSLCDYLKGNVISW--NELCKIAESMARGLAYLhEDIPAtngghkpsiAHRDFKSKNVLLKSDLTACIADFG 147
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
 649-949 2.33e-05

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 47.43  E-value: 2.33e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  649 SLGAGRFGDLCCGCLQlpgrqELPVAVHTLregcSDSQKLSFLAEA--LTLGQFDHSHIVRL----EGVVTRGNPLMIVT 722
Cdd:cd13998      2 VIGKGRFGEVWKASLK-----NEPVAVKIF----SSRDKQSWFREKeiYRTPMLKHENILQFiaadERDTALRTELWLVT 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTaqLMGLLPGLASAMKYL-SEM--------GYVHRGLAARRVLLSSGLICKISGFGrgpr 793
Cdd:cd13998     73 AFHPNGSL*DYLSLHTIDWVS--LCRLALSVARGLAHLhSEIpgctqgkpAIAHRDLKSKNILVKNDGTCCIADFG---- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  794 draeavyttmvrssllwphmllllsaiptgpmvyiLALPPSlPGLFPLVVPCLSQPGSflrcggsgrspALWAAPETL-- 871
Cdd:cd13998    147 -----------------------------------LAVRLS-PSTGEEDNANNGQVGT-----------KRYMAPEVLeg 179

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  872 --QFGHFSS--ASDVWSFGIVMWEVM-----AFGERPYWDMSGQDVIK-----------AVEDGFRlP--PPR--NCPS- 926
Cdd:cd13998    180 aiNLRDFESfkRVDIYAMGLVLWEMAsrctdLFGIVEEYKPPFYSEVPnhpsfedmqevVVRDKQR-PniPNRwlSHPGl 258

                          330       340       350
                   ....*....|....*....|....*....|.
gi 1958775623  927 -QLHRLMLECWQKDPGER-------PRFSQI 949
Cdd:cd13998    259 qSLAETIEECWDHDAEARltaqcieERLSEF 289
PHA02988 PHA02988
hypothetical protein; Provisional
 873-958 2.34e-05

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 47.43  E-value: 2.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  873 FGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKA-VEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPrfsQIHS 951
Cdd:PHA02988   196 FSEYTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLiINKNNSLKLPLDCPLEIKCIVEACTSHDSIKRP---NIKE 271


                   ....*..
gi 1958775623  952 ILSKMGQ 958
Cdd:PHA02988   272 ILYNLSL 278
SAM_Samd5 cd09527
SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a ...
 989-1047 2.60e-05

SAM domain of Samd5 subfamily; SAM (sterile alpha motif) domain of Samd5 subfamily is a putative protein-protein interaction domain. Proteins of this subfamily have a SAM domain at the N-terminus. SAM is a widespread domain in signaling and regulatory proteins. In many cases SAM mediates dimerization/oligomerization. The exact function of proteins belonging to this subfamily is unknown.


Pssm-ID: 188926  Cd Length: 63  Bit Score: 42.82  E-value: 2.60e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  989 GSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09527      3 NIVYDWLRTLQLEQYAEKFVDNGYDDLEVCKQIGDPDLDAIGVMNPAHRKRILEAVRRL 61
COG3979 COG3979
Chitodextrinase [Carbohydrate transport and metabolism];
465-575 2.85e-05

Chitodextrinase [Carbohydrate transport and metabolism];


Pssm-ID: 443178 [Multi-domain]  Cd Length: 369  Bit Score: 47.84  E-value: 2.85e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  465 VEPQSVSLSWRepvpAGASGTNRTEYEIryYEKGQSEQTYstvkTGAPAVTVTNLKPATRYVFQIRAASPGPSWEAqsfs 544
Cdd:COG3979     14 VTSSSVSLSWD----ASTDNVGVTGYDV--YRGGDQVATV----TGLTAWTVTGLTPGTEYTFTVGACDAAGNVSA---- 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1958775623  545 PSIEVQTPGEVAPGSRDQSPAVVVTVVTISA 575
Cdd:COG3979     80 ASGTSTAMFGGSSTTLGSAEGVADTSGNLAA 110
STKc_phototropin_like cd05574
Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 691-943 2.87e-05

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270726 [Multi-domain]  Cd Length: 316  Bit Score: 47.23  E-value: 2.87e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  691 LAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFL-------------RHHEAELVTAqlmgllpglasaM 757
Cdd:cd05574     49 LTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPGGELFRLLqkqpgkrlpeevaRFYAAEVLLA------------L 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  758 KYLSEMGYVHRGLAARRVLL-SSGLICkISGFgrgprDRAeavyttmvrssllwphmllLLSAIPTGPMVYILALPPSLP 836
Cdd:cd05574    117 EYLHLLGFVYRDLKPENILLhESGHIM-LTDF-----DLS-------------------KQSSVTPPPVRKSLRKGSRRS 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  837 GLFPLVVPCLSQPGSFlrcggsgRSPAL-----WAAPETLQ-FGHfSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIK 910
Cdd:cd05574    172 SVKSIEKETFVAEPSA-------RSNSFvgteeYIAPEVIKgDGH-GSAVDWWTLGILLYE-MLYGTTPFKGSNRDETFS 242

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1958775623  911 AVEDG-FRLPPPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd05574    243 NILKKeLTFPESPPVSSEAKDLIRKLLVKDPSKR 276
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
 674-899 3.09e-05

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 47.13  E-value: 3.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  674 AVHTLREGCS---DSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA--ELVTAQLMG 748
Cdd:cd14159     20 AVKRLKEDSEldwSVVKNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGSLEDRLHCQVScpCLSWSQRLH 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  749 LLPGLASAMKYLSEM--GYVHRGLAARRVLLSSGLICKISGFG--RGPRDRAEAVYTTMVrssllwphmllLLSAIPTGP 824
Cdd:cd14159    100 VLLGTARAIQYLHSDspSLIHGDVKSSNILLDAALNPKLGDFGlaRFSRRPKQPGMSSTL-----------ARTQTVRGT 168

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  825 MVYilaLPpslpglfplvvpclsqpgsflrcggsgrspalwaaPETLQFGHFSSASDVWSFGIVMWEVMAfGERP 899
Cdd:cd14159    169 LAY---LP-----------------------------------EEYVKTGTLSVEIDVYSFGVVLLELLT-GRRA 204
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
 869-958 6.08e-05

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 46.20  E-value: 6.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  869 ETLQFGHFSS--ASDVWSFGIVMWEV---------MAFGERPYWDMSGQD----------VIKAVEDGFrlpPPR----N 923
Cdd:cd14219    188 ESLNRNHFQSyiMADMYSFGLILWEVarrcvsggiVEEYQLPYHDLVPSDpsyedmreivCIKRLRPSF---PNRwssdE 264

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1958775623  924 CPSQLHRLMLECWQKDPGERPRFSQIHSILSKMGQ 958
Cdd:cd14219    265 CLRQMGKLMTECWAHNPASRLTALRVKKTLAKMSE 299
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
 693-949 6.42e-05

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 45.85  E-value: 6.42e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDD------FLRHHEAELVTAQLMgllpglaSAMKYLSEMGYV 766
Cdd:cd14084     61 EIEILKKLSHPCIIKIEDFFDAEDDYYIVLELMEGGELFDrvvsnkRLKEAICKLYFYQML-------LAVKYLHSNGII 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  767 HRGLAARRVLLSSG---LICKISGFGrgprdraeavyttmvrssllwphmlllLSAIptgpmvyilalppslpglfplvv 843
Cdd:cd14084    134 HRDLKPENVLLSSQeeeCLIKITDFG---------------------------LSKI----------------------- 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  844 pclSQPGSFLR--CGgsgrSPaLWAAPETLQFGH---FSSASDVWSFGIVMWeVMAFGERP----YWDMSGQDVIKAVED 914
Cdd:cd14084    164 ---LGETSLMKtlCG----TP-TYLAPEVLRSFGtegYTRAVDCWSLGVILF-ICLSGYPPfseeYTQMSLKEQILSGKY 234

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1958775623  915 GFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd14084    235 TFIPKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEA 269
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
 690-907 8.17e-05

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 45.76  E-value: 8.17e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  690 FLAEALTLGQFDHSHIVR-LEGVVTRGNPLMIVTEYMNLGAL------DDFLRHHEAELVTAQLMgllpglaSAMKYLSE 762
Cdd:cd13994     44 LTSEYIISSKLHHPNIVKvLDLCQDLHGKWCLVMEYCPGGDLftliekADSLSLEEKDCFFKQIL-------RGVAYLHS 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  763 MGYVHRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrssllwphmllllsaiptgpmvyilalppslpglfplV 842
Cdd:cd13994    117 HGIAHRDLKPENILLDEDGVLKLTDFG----------------------------------------------------T 144

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  843 VPCLSQPG---SFLRCGGSGRSPALwaAPETLQFGHFS-SASDVWSFGIVMWeVMAFGERPyWDMSGQD 907
Cdd:cd13994    145 AEVFGMPAekeSPMSAGLCGSEPYM--APEVFTSGSYDgRAVDVWSCGIVLF-ALFTGRFP-WRSAKKS 209
SAM_DGK-delta cd09575
SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta ...
 991-1047 9.16e-05

SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK-delta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. In particular DGK-delta is involved in the regulation of clathrin-dependent endocytosis. The SAM domain of DGK-delta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-eta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it inhibits the translocation of the protein to the plasma membrane from the cytoplasm. The SAM domain also can bind Zn at multiple (not conserved) sites driving the formation of highly ordered large sheets of polymers, thus suggesting that Zn may play important role in the function of DCK-delta.


Pssm-ID: 188974  Cd Length: 65  Bit Score: 41.47  E-value: 9.16e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958775623  991 VGAWLEALDLCRYKDNFSAAGYGSLEaVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09575     10 VAAWLEHLSLCEYKDIFTRHDVRGSE-LLHLERRDLKDLGVTKVGHMKRILCGIKEL 65
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 646-956 9.37e-05

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 45.79  E-value: 9.37e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGDLCCGCLQLPGrqeLPVAVHTLR--EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd08229     28 IEKKIGRGQFSEVYRATCLLDG---VPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLE 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  724 YMNLGALDDFLRHHEAE---LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGprdRAEAVY 800
Cdd:cd08229    105 LADAGDLSRMIKHFKKQkrlIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLG---RFFSSK 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  801 TTMVRSsllwphmllllsaiptgpmvyILALPpslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSAS 880
Cdd:cd08229    182 TTAAHS---------------------LVGTP-------------------------------YYMSPERIHENGYNFKS 209

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  881 DVWSFGIVMWEVMAFGERPYWD-MSGQDVIKAVEDGFRLPPPRNCPSQ-LHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd08229    210 DIWSLGCLLYEMAALQSPFYGDkMNLYSLCKKIEQCDYPPLPSDHYSEeLRQLVNMCINPDPEKRPDITYVYDVAKRM 287
SAM_KIF24-like cd09541
SAM domain of KIF24-like subfamily; SAM (sterile alpha motif) domain of KIF24 subfamily is a ...
 994-1040 1.08e-04

SAM domain of KIF24-like subfamily; SAM (sterile alpha motif) domain of KIF24 subfamily is a putative protein-protein interaction domain. This subfamily includes proteins related to human kinesin-like protein KIF24. SAM domain is located at the N-terminus followed by kinesin motor domain. Kinesins are proteins involved in a number of different cell processes including microtubule dynamics and axonal transport. Kinesins of this group belong to N-type; they drive microtubule plus end-directed transport. SAM apparently plays the role of adaptor or scaffold domain. In many cases SAM is known as a mediator of dimerization/oligomerization.


Pssm-ID: 188940  Cd Length: 60  Bit Score: 41.13  E-value: 1.08e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1958775623  994 WLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREAL 1040
Cdd:cd09541      6 WLEEAGLQHYYPAFAAGGVTSIEALAQLTMQDYASLGVQDMEDKQKL 52
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
 696-789 1.08e-04

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 45.17  E-value: 1.08e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  696 TLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGaLDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRV 775
Cdd:cd07829     51 LLKELKHPNIVKLLDVIHTENKLYLVFEYCDQD-LKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNL 129

                           90
                   ....*....|....
gi 1958775623  776 LLSSGLICKISGFG 789
Cdd:cd07829    130 LINRDGVLKLADFG 143
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 863-949 1.11e-04

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 45.44  E-value: 1.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  863 ALWAAPETL---QFGHFSSASDVWSFGIVMWEvMAFGERPY--WDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLE-CW 936
Cdd:cd06618    178 AAYMAPERIdppDNPKYDIRADVWSLGISLVE-LATGQFPYrnCKTEFEVLTKILNEEPPSLPPNEGFSPDFCSFVDlCL 256

                           90
                   ....*....|...
gi 1958775623  937 QKDPGERPRFSQI 949
Cdd:cd06618    257 TKDHRYRPKYREL 269
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
 702-949 1.12e-04

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 45.01  E-value: 1.12e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  702 HSHIVRLEGVVTRGNPLMIVTEYMNLGAL------DDFLRHHEAELVTAQLMgllpglaSAMKYLSEMGYVHRGLAARRV 775
Cdd:cd14069     59 HKNVVRFYGHRREGEFQYLFLEYASGGELfdkiepDVGMPEDVAQFYFQQLM-------AGLKYLHSCGITHRDIKPENL 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  776 LLSSGLICKISGFGrgprdraeavYTTMVRSSLLWPHmllllsaiptgpmvyilalppslpglfpLVVPCLSQPgsflrc 855
Cdd:cd14069    132 LLDENDNLKISDFG----------LATVFRYKGKERL----------------------------LNKMCGTLP------ 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  856 ggsgrspalWAAPETLQ-FGHFSSASDVWSFGIVMWeVMAFGERPyWDM---SGQDVIKAVEDGFrlppPRNCP------ 925
Cdd:cd14069    168 ---------YVAPELLAkKKYRAEPVDVWSCGIVLF-AMLAGELP-WDQpsdSCQEYSDWKENKK----TYLTPwkkidt 232

                          250       260
                   ....*....|....*....|....*..
gi 1958775623  926 ---SQLHRLMLEcwqkDPGERPRFSQI 949
Cdd:cd14069    233 aalSLLRKILTE----NPNKRITIEDI 255
SAM_Ship2 cd09491
SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 ...
 990-1044 1.15e-04

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.


Pssm-ID: 188890  Cd Length: 63  Bit Score: 40.97  E-value: 1.15e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGI 1044
Cdd:cd09491      7 TVSEWLMNLGLQQYEEGLMHNGWDSLEFLSDITEEDLEEAGVTNPAHKRRLLDSL 61
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
 691-944 1.35e-04

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 44.75  E-value: 1.35e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  691 LAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMnLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGL 770
Cdd:cd06607     49 IKEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEYC-LGSASDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDV 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  771 AARRVLLSSGLICKISGFGrgprdraeavyttmvrssllwphmllllSAiptgpmvyilalppslpglfPLVVPCLSQPG 850
Cdd:cd06607    128 KAGNILLTEPGTVKLADFG----------------------------SA--------------------SLVCPANSFVG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  851 SflrcggsgrspALWAAPE---TLQFGHFSSASDVWSFGIVMWEVmafGER--PYWDMSGQDVIK--AVEDGFRLPPprN 923
Cdd:cd06607    160 T-----------PYWMAPEvilAMDEGQYDGKVDVWSLGITCIEL---AERkpPLFNMNAMSALYhiAQNDSPTLSS--G 223

                          250       260
                   ....*....|....*....|..
gi 1958775623  924 CPSQLHRLMLE-CWQKDPGERP 944
Cdd:cd06607    224 EWSDDFRNFVDsCLQKIPQDRP 245
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 675-944 1.38e-04

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 44.73  E-value: 1.38e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  675 VHTLREGCSDSQKL--SFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEA---ELVTAQLMGL 749
Cdd:cd06630     33 VSFCRNSSSEQEEVveAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLLSKYGAfseNVIINYTLQI 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  750 LPGLAsamkYLSEMGYVHRGLAARRVLL-SSGLICKISGFGRGPRdraeavyttmvrssllwphmllllsaiptgpmvyi 828
Cdd:cd06630    113 LRGLA----YLHDNQIIHRDLKGANLLVdSTGQRLRIADFGAAAR----------------------------------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  829 LALPPSLPGLFplvvpclsqPGSFLrcggsgrSPALWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPyWDMSGQD- 907
Cdd:cd06630    154 LASKGTGAGEF---------QGQLL-------GTIAFMAPEVLRGEQYGRSCDVWSVGCVIIE-MATAKPP-WNAEKISn 215

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1958775623  908 ---VIKAVEDGFRLPP-PRNCPSQLHRLMLECWQKDPGERP 944
Cdd:cd06630    216 hlaLIFKIASATTPPPiPEHLSPGLRDVTLRCLELQPEDRP 256
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
 857-956 1.44e-04

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 45.03  E-value: 1.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  857 GSGRSPALWAAPETLQFGHFSS--ASDVWSFGIVMWE---------VMAFGERPYWDM-----SGQDVIKAVEDGFRLPP 920
Cdd:cd14220    166 GTKRYMAPEVLDESLNKNHFQAyiMADIYSFGLIIWEmarrcvtggIVEEYQLPYYDMvpsdpSYEDMREVVCVKRLRPT 245

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958775623  921 PRN------CPSQLHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14220    246 VSNrwnsdeCLRAVLKLMSECWAHNPASRLTALRIKKTLAKM 287
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
 693-949 1.61e-04

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 44.75  E-value: 1.61e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDF------LRHHEAELVTAQlmgllpgLASAMKYLSEMGYV 766
Cdd:cd14077     63 EAALSSLLNHPHICRLRDFLRTPNHYYMLFEYVDGGQLLDYiishgkLKEKQARKFARQ-------IASALDYLHRNSIV 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  767 HRGLAARRVLLSSGLICKISGFGrgprdraeavyttmvrssllwphmllllsaiptgpmvyilalppsLPGLFplvvpcl 846
Cdd:cd14077    136 HRDLKIENILISKSGNIKIIDFG---------------------------------------------LSNLY------- 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  847 sQPGSFLR--CGGsgrspALWAAPETLQFGHFSSAS-DVWSFGIVMWeVMAFGERPYWDMSGQDVIKAVEDG-FRLPP-- 920
Cdd:cd14077    164 -DPRRLLRtfCGS-----LYFAAPELLQAQPYTGPEvDVWSFGVVLY-VLVCGKVPFDDENMPALHAKIKKGkVEYPSyl 236

                          250       260
                   ....*....|....*....|....*....
gi 1958775623  921 PRNCPSQLHRLMLecwqKDPGERPRFSQI 949
Cdd:cd14077    237 SSECKSLISRMLV----VDPKKRATLEQV 261
SAM_tumor-p63,p73 cd09503
SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 ...
 989-1044 1.70e-04

SAM domain of tumor-p63,p73 proteins; SAM (sterile alpha motif) domain of p63, p73 transcriptional factors is a putative protein-protein interaction domain and lipid-binding domain. p63 and p73 are homologs to the tumor suppressor p53. They have a C-terminal SAM domain in their longest spliced alpha forms, while p53 doesn't have it. p63 or p73 knockout mice show significant developmental abnormalities but no increased cancer susceptibility, suggesting that p63 and p73 play a role in regulation of normal development. It was shown that SAM domain of p73 is able to bind some membrane lipids. The structural rearrangements in SAM are necessary to accomplish the binding. No evidence for homooligomerization through SAM domains was found for p63/p73 subfamily. It was suggested that the partner proteins should be either more distantly related SAM-containing domain proteins or proteins without the SAM domain.


Pssm-ID: 188902  Cd Length: 65  Bit Score: 40.76  E-value: 1.70e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  989 GSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSaEHREALLSGI 1044
Cdd:cd09503      5 NSVASWLTKLGCSNYIDNFHQQGLLSIFQLDEFTLEDLAAMKIPE-QHRNKIWKGL 59
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 867-943 1.79e-04

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 44.43  E-value: 1.79e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDmSGQDVI--KAVEDGFRLPPprNCPSQLHRLMLECWQKDPGER 943
Cdd:cd05123    161 APEVLLGKGYGKAVDWWSLGVLLYE-MLTGKPPFYA-ENRKEIyeKILKSPLKFPE--YVSPEAKSLISGLLQKDPTKR 235
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
 718-943 1.80e-04

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 44.74  E-value: 1.80e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYL--------SEMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd14143     68 LWLVSDYHEHGSLFDYLNRYT--VTVEGMIKLALSIASGLAHLhmeivgtqGKPAIAHRDLKSKNILVKKNGTCCIADLG 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  790 RGPRDraEAVYTTMvrssllwphmllllsAIPTGPMVyilalppslpglfplvvpclsqpgsflrcgGSGRspalWAAPE 869
Cdd:cd14143    146 LAVRH--DSATDTI---------------DIAPNHRV------------------------------GTKR----YMAPE 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  870 ----TLQFGHFSS--ASDVWSFGIVMWEVmafGER------------PYWDM-----SGQDVIKAV-EDGFRlPpprNCP 925
Cdd:cd14143    175 vlddTINMKHFESfkRADIYALGLVFWEI---ARRcsiggihedyqlPYYDLvpsdpSIEEMRKVVcEQKLR-P---NIP 247

                          250       260
                   ....*....|....*....|....*..
gi 1958775623  926 SQLH---------RLMLECWQKDPGER 943
Cdd:cd14143    248 NRWQscealrvmaKIMRECWYANGAAR 274
SAM_EPH-A3 cd09544
SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain ...
 987-1049 1.89e-04

SAM domain of EPH-A3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A3 subfamily of receptor tyrosine kinases is a C-terminal putative protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A3 receptors bind SH2/SH3 containing adaptor protein Nck1 and this adaptor is a key factor in EPH-A3 mediated signaling. However SAM domain is not implemented in this interaction. Activation of EPH-A3 receptors inhibits outgrowth and cell migration. Mutations in SAM domain may play a role in development of hepatocellular carcinoma. Expression of EPH-A3 is associated with lymphocytic leukemia and defines the subset of rhabdomyosarcoma tumors. EPH-A3 receptors are attractive targets for drug design.


Pssm-ID: 188943  Cd Length: 63  Bit Score: 40.42  E-value: 1.89e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  987 SFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISALQT 1049
Cdd:cd09544      1 TFHTTGDWLNGARTAHCKEIFTGVEYSSCDTIAKISTDDMKKVGVTVVGPQKKIVSSIKTLET 63
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
 683-789 1.95e-04

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 44.34  E-value: 1.95e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  683 SDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLS 761
Cdd:cd08221     39 SEKERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGNLHDKIAQQKNQLFPeEVVLWYLYQIVSAVSHIH 118

                           90       100
                   ....*....|....*....|....*...
gi 1958775623  762 EMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd08221    119 KAGILHRDIKTLNIFLTKADLVKLGDFG 146
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
 693-949 2.07e-04

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 44.32  E-value: 2.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLRHHEAELVTAQ---------LMGLLpglasamkYLSEM 763
Cdd:cd08529     49 EARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAENGDLHSLIKSQRGRPLPEDqiwkffiqtLLGLS--------HLHSK 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  764 GYVHRGLAARRVLLSSGLICKISGFGRgprdrAEAVYTTMVRSSLlwphmllllsaiptgpmvyILALPPSLpglfplvv 843
Cdd:cd08529    121 KILHRDIKSMNIFLDKGDNVKIGDLGV-----AKILSDTTNFAQT-------------------IVGTPYYL-------- 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  844 pclsqpgsflrcggsgrspalwaAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDGFRLPPPRN 923
Cdd:cd08529    169 -----------------------SPELCEDKPYNEKSDVWALGCVLYE-LCTGKHPFEAQNQGALILKIVRGKYPPISAS 224

                          250       260
                   ....*....|....*....|....*.
gi 1958775623  924 CPSQLHRLMLECWQKDPGERPRFSQI 949
Cdd:cd08529    225 YSQDLSQLIDSCLTKDYRQRPDTTEL 250
Pur_ac_phosph_N pfam16656
Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple ...
 467-543 2.46e-04

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.


Pssm-ID: 465220 [Multi-domain]  Cd Length: 93  Bit Score: 41.24  E-value: 2.46e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  467 PQSVSLSWREPVPAGASgtnRTEYEIRYYEKGQSEQTYSTVKTGAPA-------VTVTNLKPATRYVFQIRAASPGPSwE 539
Cdd:pfam16656   12 STSMTVSWVTPSAVTSP---VVQYGTSSSALTSTATATSSTYTTGDGgtgyihrATLTGLEPGTTYYYRVGDDNGGWS-E 87


                   ....
gi 1958775623  540 AQSF 543
Cdd:pfam16656   88 VYSF 91
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
 645-949 2.89e-04

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 44.06  E-value: 2.89e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQLPGrqELpVAVHTLRegcsdsQKLSFLAEALTLGQF-------DHSHIVRLEGVVTRGNP 717
Cdd:cd07830      2 KVIKQLGDGTFGSVYLARNKETG--EL-VAIKKMK------KKFYSWEECMNLREVkslrklnEHPNIVKLKEVFRENDE 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNlGALDDFLRHHEAELVT-AQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG--RGPRD 794
Cdd:cd07830     73 LYFVFEYME-GNLYQLMKDRKGKPFSeSVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGlaREIRS 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  795 RaeAVYTTMVrssllwphmllllsaiptgpmvyilalppslpglfplvvpclsqpgsflrcggSGRspalW-AAPET-LQ 872
Cdd:cd07830    152 R--PPYTDYV-----------------------------------------------------STR----WyRAPEIlLR 172

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  873 FGHFSSASDVWSFGIVMWEVMAFgeRP------------------------YWDmSGQDVIKAVedGFRLPP-------- 920
Cdd:cd07830    173 STSYSSPVDIWALGCIMAELYTL--RPlfpgsseidqlykicsvlgtptkqDWP-EGYKLASKL--GFRFPQfaptslhq 247

                          330       340       350
                   ....*....|....*....|....*....|.
gi 1958775623  921 --PRNCPSQLHrLMLECWQKDPGERPRFSQI 949
Cdd:cd07830    248 liPNASPEAID-LIKDMLRWDPKKRPTASQA 277
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
 667-789 3.01e-04

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 43.80  E-value: 3.01e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  667 GRQELPVAvhTLREgcsdsqkLSFLAEaltLGQFDHSHIVRLEGV-----VTRGNPLMIVTEYMNLGaLDDFLRHH-EAE 740
Cdd:cd07838     37 SEEGIPLS--TIRE-------IALLKQ---LESFEHPNVVRLLDVchgprTDRELKLTLVFEHVDQD-LATYLDKCpKPG 103

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1958775623  741 LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd07838    104 LPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFG 152
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
 645-951 3.11e-04

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 43.69  E-value: 3.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  645 TLEKSLGAGRFGDLCCGCLQlpgRQELPVAVHTL--REGCSDSQKLSFLAEALTLGQFDHSHIVRL-EGVVTRGNPLMIV 721
Cdd:cd14164      3 TLGTTIGEGSFSKVKLATSQ---KYCCKVAIKIVdrRRASPDFVQKFLPRELSILRRVNHPNIVQMfECIEVANGRLYIV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  722 TEYMNLGALDDFLRHHEAELVTAQLMglLPGLASAMKYLSEMGYVHRGLAARRVLLSS-GLICKIS--GFGRGPRDraea 798
Cdd:cd14164     80 MEAAATDLLQKIQEVHHIPKDLARDM--FAQMVGAVNYLHDMNIVHRDLKCENILLSAdDRKIKIAdfGFARFVED---- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  799 vyttmvrssllwphmllllsaiptgpmvyilalPPSLPGLFplvvpclsqpgsflrCGGsgrspALWAAPET-LQFGHFS 877
Cdd:cd14164    154 ---------------------------------YPELSTTF---------------CGS-----RAYTPPEViLGTPYDP 180

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  878 SASDVWSFGIVMWeVMAFGERPYwDMSGQDVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHS 951
Cdd:cd14164    181 KKYDVWSLGVVLY-VMVTGTMPF-DETNVRRLRLQQRGVLYPSGVALEEPCRALIRTLLQFNPSTRPSIQQVAG 252
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
 718-956 3.35e-04

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 44.00  E-value: 3.35e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  718 LMIVTEYMNLGALDDFLRHHEaeLVTAQLMGLLPGLASAMKYL-SEM-------GYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd14144     68 LYLITDYHENGSLYDFLRGNT--LDTQSMLKLAYSAACGLAHLhTEIfgtqgkpAIAHRDIKSKNILVKKNGTCCIADLG 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  790 RGPRDRAEavyTTMVRssllwphmllllsaIPTGPMVyilalppslpglfplvvpclsqpgsflrcgGSGRSPALWAAPE 869
Cdd:cd14144    146 LAVKFISE---TNEVD--------------LPPNTRV------------------------------GTKRYMAPEVLDE 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  870 TLQFGHFSS--ASDVWSFGIVMWEV----MAFG-----ERPYWDM-----SGQDVIKAV-EDGFRLPPPR-----NCPSQ 927
Cdd:cd14144    179 SLNRNHFDAykMADMYSFGLVLWEIarrcISGGiveeyQLPYYDAvpsdpSYEDMRRVVcVERRRPSIPNrwssdEVLRT 258

                          250       260
                   ....*....|....*....|....*....
gi 1958775623  928 LHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd14144    259 MSKLMSECWAHNPAARLTALRVKKTLGKL 287
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
 650-900 3.92e-04

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 43.80  E-value: 3.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  650 LGAGRFGDLCCGCLQLPGRQelpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVR-------LEGVVTRGNPLMIVt 722
Cdd:cd14038      2 LGTGGFGNVLRWINQETGEQ---VAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVVAardvpegLQKLAPNDLPLLAM- 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  723 EYMNLGALDDFLRHHE--AELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSG---LICKISGFGRGPRDRAE 797
Cdd:cd14038     78 EYCQGGDLRKYLNQFEncCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQGeqrLIHKIIDLGYAKELDQG 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  798 AVYTTMVrssllwphmllllsaiptGPMVYIlalppslpglfplvvpclsqpgsflrcggsgrspalwaAPETLQFGHFS 877
Cdd:cd14038    158 SLCTSFV------------------GTLQYL--------------------------------------APELLEQQKYT 181

                          250       260
                   ....*....|....*....|...
gi 1958775623  878 SASDVWSFGIVMWEVMAfGERPY 900
Cdd:cd14038    182 VTVDYWSFGTLAFECIT-GFRPF 203
SAM_DGK-delta-eta cd09507
SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain ...
 991-1047 4.60e-04

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.


Pssm-ID: 188906  Cd Length: 65  Bit Score: 39.32  E-value: 4.60e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958775623  991 VGAWLEALDLCRYKDNFS-----AAGYGSLEavtemtAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09507     10 VGAWLESLQLGEYRDIFArndirGSELLHLE------RRDLKDLGITKVGHVKRILQAIKDL 65
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
 868-952 6.02e-04

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 43.03  E-value: 6.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  868 PETLQFGHFSSASDVWSFGIVMWEVMAFGERPYWD-MSGQDVIKAVEDGFRLPPPRNC-PSQLHRLMLECWQKDPGERPR 945
Cdd:cd08224    173 PERIREQGYDFKSDIWSLGCLLYEMAALQSPFYGEkMNLYSLCKKIEKCEYPPLPADLySQELRDLVAACIQPDPEKRPD 252


                   ....*..
gi 1958775623  946 FSQIHSI 952
Cdd:cd08224    253 ISYVLDV 259
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
 646-956 7.24e-04

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 42.71  E-value: 7.24e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  646 LEKSLGAGRFGDLCCGCLQLpGRQELPVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd08228      6 IEKKIGRGQFSEVYRATCLL-DRKPVALKKVQIFEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLELA 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  726 NLGALDDFLRHHEAE---LVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFGRGprdRAEAVYTT 802
Cdd:cd08228     85 DAGDLSQMIKYFKKQkrlIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLG---RFFSSKTT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  803 MVRSsllwphmllllsaiptgpmvyILALPpslpglfplvvpclsqpgsflrcggsgrspaLWAAPETLQFGHFSSASDV 882
Cdd:cd08228    162 AAHS---------------------LVGTP-------------------------------YYMSPERIHENGYNFKSDI 189

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  883 WSFGIVMWEVMAFGERPYWD-MSGQDVIKAVEDGFRLPPPRNCPSQ-LHRLMLECWQKDPGERPRFSQIHSILSKM 956
Cdd:cd08228    190 WSLGCLLYEMAALQSPFYGDkMNLFSLCQKIEQCDYPPLPTEHYSEkLRELVSMCIYPDPDQRPDIGYVHQIAKQM 265
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
 647-779 7.71e-04

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 42.40  E-value: 7.71e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  647 EKSLGAGRFGDLCCGCLQLPGRQelpVAVHTL-REGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYM 725
Cdd:cd14082      8 DEVLGSGQFGIVYGGKHRKTGRD---VAIKVIdKLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKL 84

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1958775623  726 NLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLLSS 779
Cdd:cd14082     85 HGDMLEMILSSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLAS 138
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
 673-804 7.84e-04

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 42.69  E-value: 7.84e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLREGCSDSQ-KLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDF------LRHHEAELVTAQ 745
Cdd:cd07833     29 VAIKKFKESEDDEDvKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYVERTLLELLeaspggLPPDAVRSYIWQ 108

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  746 LMgllpglaSAMKYLSEMGYVHRGLAARRVLLSSGLICKIS--GFGRGPRDRAEAVYTTMV 804
Cdd:cd07833    109 LL-------QAIAYCHSHNIIHRDIKPENILVSESGVLKLCdfGFARALTARPASPLTDYV 162
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
 867-953 8.22e-04

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 42.48  E-value: 8.22e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQfGHFSSASDVWSFGIVMWEVMAFGER-PYWD---MSGQDVIKAVEDGFRlppPRNCPS---QLHRLMLECWQKD 939
Cdd:cd13975    167 APELFS-GKYDNSVDVYAFGILFWYLCAGHVKlPEAFeqcASKDHLWNNVRKGVR---PERLPVfdeECWNLMEACWSGD 242

                           90
                   ....*....|....
gi 1958775623  940 PGERPRFSQIHSIL 953
Cdd:cd13975    243 PSQRPLLGIVQPKL 256
SAM_SASH1_repeat2 cd09492
SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins ...
 990-1047 8.72e-04

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.


Pssm-ID: 188891  Cd Length: 70  Bit Score: 39.03  E-value: 8.72e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGISAL 1047
Cdd:cd09492      9 SVSDWLVSIGLPMYSPPLLEAGFSTLSRVSSLSETCLREAGITEERHIRKLLSAARLV 66
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
 643-793 9.32e-04

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 42.21  E-value: 9.32e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  643 SVTLEKSLGAGRFGDLCCgCLQlpGRQELPVAVHTLREGCSDSQKLSFLaEALTLGQFDHSHIVRLEGVVTRGNPLMIVT 722
Cdd:cd14190      5 SIHSKEVLGGGKFGKVHT-CTE--KRTGLKLAAKVINKQNSKDKEMVLL-EIQVMNQLNHRNLIQLYEAIETPNEIVLFM 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958775623  723 EYMNLGALDDFLRHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAARRVLL--SSGLICKISGFGRGPR 793
Cdd:cd14190     81 EYVEGGELFERIVDEDYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARR 153
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
 865-943 1.31e-03

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 42.30  E-value: 1.31e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAV-EDGFRLppPRNCPSQLHRLMLECWQKDPGER 943
Cdd:cd05595    161 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHERLFELIlMEEIRF--PRTLSPEAKSLLAGLLKKDPKQR 237
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
 856-900 1.48e-03

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 41.47  E-value: 1.48e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1958775623  856 GGSGRSPalWAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPY 900
Cdd:cd05578    158 STSGTKP--YMAPEVFMRAGYSFAVDWWSLGVTAYE-MLRGKRPY 199
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
 867-949 1.81e-03

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 41.31  E-value: 1.81e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDVIKAVEDG-FRLPPPrncPSQLHR-LMLECWQKDPGERP 944
Cdd:cd14007    166 PPEMVEGKEYDYKVDIWSLGVLCYE-LLVGKPPFESKSHQETYKRIQNVdIKFPSS---VSPEAKdLISKLLQKDPSKRL 241


                   ....*
gi 1958775623  945 RFSQI 949
Cdd:cd14007    242 SLEQV 246
COG4733 COG4733
Phage-related protein, tail protein J [Mobilome: prophages, transposons];
420-532 1.83e-03

Phage-related protein, tail protein J [Mobilome: prophages, transposons];


Pssm-ID: 443767 [Multi-domain]  Cd Length: 978  Bit Score: 42.24  E-value: 1.83e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  420 RYTVRVAALN--GVSGPaaAAGATYAQVTVSTG-PGAPweeDEIrrdRVEPQ--SVSLSWREPVpagasGTNRTEYEIRY 494
Cdd:COG4733    598 DYEVRVRAINalGVSSA--WAASSETTVTGKTApPPAP---TGL---TATGGlgGITLSWSFPV-----DADTLRTEIRY 664

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1958775623  495 YEKGQ-SEQTYSTVKTGAPAVTVTNLKPATRYVFQIRAA 532
Cdd:COG4733    665 STTGDwASATVAQALYPGNTYTLAGLKAGQTYYYRARAV 703
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 880-949 2.16e-03

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 41.20  E-value: 2.16e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958775623  880 SDVWSFGIVMWEVmAFGERPY--WdMSGQDVIKAVEDGfrlPPPRNCPSQLHRLMLE-------CWQKDPGERPRFSQI 949
Cdd:cd06616    194 SDVWSLGITLYEV-ATGKFPYpkW-NSVFDQLTQVVKG---DPPILSNSEEREFSPSfvnfvnlCLIKDESKRPKYKEL 267
SAM_AIDA1AB-like_repeat2 cd09500
SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of ...
 986-1045 2.32e-03

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188899  Cd Length: 65  Bit Score: 37.28  E-value: 2.32e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958775623  986 PSFGSVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGS-LGISSAEHREALLSGIS 1045
Cdd:cd09500      3 NSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNvLEINKLGHRKRILASLA 63
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
 880-955 2.43e-03

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 41.17  E-value: 2.43e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958775623  880 SDVWSFGIVMWeVMAFGERPYWDMSgqdVIKAVEDGFRLPPPRNCPSQLHRLMLECWQKDPGERPRFSQIHSILSK 955
Cdd:cd13985    198 ADIWALGCLLY-KLCFFKLPFDESS---KLAIVAGKYSIPEQPRYSPELHDLIRHMLTPDPAERPDIFQVINIITK 269
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
 865-944 3.23e-03

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 40.72  E-value: 3.23e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVEDGFRlpPPRNCPSQ-----LHRLMLECWQKD 939
Cdd:cd14067    183 YQAPEIRPRIVYDEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLSKGIR--PVLGQPEEvqffrLQALMMECWDTK 259


                   ....*
gi 1958775623  940 PGERP 944
Cdd:cd14067    260 PEKRP 264
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
 865-957 3.87e-03

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 40.60  E-value: 3.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETL------QFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQDV---IKAVEDGfrlPPPRNCPS---QLHRLM 932
Cdd:cd06622    167 YMAPERIksggpnQNPTYTVQSDVWSLGLSILE-MALGRYPYPPETYANIfaqLSAIVDG---DPPTLPSGysdDAQDFV 242

                           90       100
                   ....*....|....*....|....*..
gi 1958775623  933 LECWQKDPGERPRFSQI--HSILSKMG 957
Cdd:cd06622    243 AKCLNKIPNRRPTYAQLleHPWLVKYK 269
SAM_Arap1,2,3 cd09490
SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) ...
 990-1044 4.05e-03

SAM domain of Arap1,2,3 (angiotensin receptor-associated protein); SAM (sterile alpha motif) domain of Arap1,2,3 subfamily proteins (angiotensin receptor-associated) is a protein-protein interaction domain. Arap1,2,3 proteins are phosphatidylinositol-3,4,5-trisphosphate-dependent GTPase-activating proteins. They are involved in phosphatidylinositol-3 kinase (PI3K) signaling pathways. In addition to SAM domain, Arap1,2,3 proteins contain ArfGap, PH-like, RhoGAP and UBQ domains. SAM domain of Arap3 protein was shown to interact with SAM domain of Ship2 phosphatidylinositol-trisphosphate phosphatase proteins. Such interaction apparently plays a role in inhibition of PI3K regulated pathways since Ship2 converts PI(3,4,5)P3 into PI(3,4)P2. Proteins of this subfamily participate in regulation of signaling and trafficking associated with a number of different receptors (including EGFR, TRAIL-R1/DR4, TRAIL-R2/DR5) in normal and cancer cells; they are involved in regulation of actin cytoskeleton remodeling, cell spreading and formation of lamellipodia.


Pssm-ID: 188889  Cd Length: 63  Bit Score: 36.89  E-value: 4.05e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1958775623  990 SVGAWLEALDLCRYKDNFSAAGYGSLEAVTEMTAQDLGSLGISSAEHREALLSGI 1044
Cdd:cd09490      5 DIAEWLASIHLEQYLDLFREHGYVTATDCQGINDSRLKQIGISPTGHRRRILKQL 59
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
 702-789 4.30e-03

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 40.48  E-value: 4.30e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  702 HSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrhheAELVTAQLM------GLLPGLASAMKYLSEMGYVHRGLAARRV 775
Cdd:cd14052     62 HDNIVQLIDSWEYHGHLYIQTELCENGSLDVFL----SELGLLGRLdefrvwKILVELSLGLRFIHDHHFVHLDLKPANV 137

                           90
                   ....*....|....
gi 1958775623  776 LLSSGLICKISGFG 789
Cdd:cd14052    138 LITFEGTLKIGDFG 151
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
 865-943 4.73e-03

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 40.45  E-value: 4.73e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAV--EDgfrLPPPRNCPSQLHRLMLECWQKDPGE 942
Cdd:cd05593    181 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMC-GRLPFYNQDHEKLFELIlmED---IKFPRTLSADAKSLLSGLLIKDPNK 256


                   .
gi 1958775623  943 R 943
Cdd:cd05593    257 R 257
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
 644-779 4.90e-03

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 40.26  E-value: 4.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  644 VTLEKSLGAGRFGDLCCGclQLPGRQELpVAVHTLREGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVTRGNPLMIVTE 723
Cdd:cd14169      5 YELKEKLGEGAFSEVVLA--QERGSQRL-VALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESPTHLYLAME 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958775623  724 YMNLGALDDFL--RHHEAELVTAQLMGLLPGlasAMKYLSEMGYVHRGLAARRVLLSS 779
Cdd:cd14169     82 LVTGGELFDRIieRGSYTEKDASQLIGQVLQ---AVKYLHQLGIVHRDLKPENLLYAT 136
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
 865-949 5.12e-03

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 39.91  E-value: 5.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEVMAfGERPYWDMSGQDVIKAVED-GFRLPPPRNCPSQlhRLMLECWQKDPGER 943
Cdd:cd14189    167 YLAPEVLLRQGHGPESDVWSLGCVMYTLLC-GNPPFETLDLKETYRCIKQvKYTLPASLSLPAR--HLLAGILKRNPGDR 243


                   ....*.
gi 1958775623  944 PRFSQI 949
Cdd:cd14189    244 LTLDQI 249
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
 673-789 5.15e-03

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 40.04  E-value: 5.15e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  673 VAVHTLR-EGCSDSQKLSFLAEALTLGQFDHSHIVRLEGVVT--RGNPLMIVTEY--MNLGALddfLRHHEAELVTAQLM 747
Cdd:cd07845     35 VALKKVRmDNERDGIPISSLREITLLLNLRHPNIVELKEVVVgkHLDSIFLVMEYceQDLASL---LDNMPTPFSESQVK 111

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958775623  748 GLLPGLASAMKYLSEMGYVHRGLAARRVLLSSGLICKISGFG 789
Cdd:cd07845    112 CLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFG 153
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
 693-789 6.09e-03

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 39.84  E-value: 6.09e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  693 EALTLGQFDHSHIVRLEGVVTRGNPLMIVTEYMNLGALDDFLrHHEAELVTAQLMGLLPGLASAMKYLSEMGYVHRGLAA 772
Cdd:cd14097     50 EVDILKHVNHAHIIHLEEVFETPKRMYLVMELCEDGELKELL-LRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKL 128

                           90       100
                   ....*....|....*....|....
gi 1958775623  773 RRVLLSSG-------LICKISGFG 789
Cdd:cd14097    129 ENILVKSSiidnndkLNIKVTDFG 152
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
 867-907 7.07e-03

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 39.68  E-value: 7.07e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1958775623  867 APETLQFGHFSSASDVWSFGIVMWEvMAFGERPYwdmSGQD 907
Cdd:cd05592    164 APEILKGQKYNQSVDWWSFGVLLYE-MLIGQSPF---HGED 200
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
 865-944 7.89e-03

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 39.48  E-value: 7.89e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQFGHFSSASDVWSFGIVMWEvMAFGERPYWDMSGQ-------DVIKAV--EDGFRLPPPRNCPSQLHrLMLEC 935
Cdd:cd06619    159 YMAPERISGEQYGIHSDVWSLGISFME-LALGRFPYPQIQKNqgslmplQLLQCIvdEDPPVLPVGQFSEKFVH-FITQC 236


                   ....*....
gi 1958775623  936 WQKDPGERP 944
Cdd:cd06619    237 MRKQPKERP 245
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
 865-949 8.87e-03

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 39.21  E-value: 8.87e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958775623  865 WAAPETLQF-----GHFSSASDVWSFGIVMWEvMAFGERPYWDMSGqdvIKAVEDGFRLPPPR-----NCPSQLHRLMLE 934
Cdd:cd06608    179 WMAPEVIACdqqpdASYDARCDVWSLGITAIE-LADGKPPLCDMHP---MRALFKIPRNPPPTlkspeKWSKEFNDFISE 254

                           90
                   ....*....|....*
gi 1958775623  935 CWQKDPGERPRFSQI 949
Cdd:cd06608    255 CLIKNYEQRPFTEEL 269
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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