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Conserved domains on  [gi|306778|gb|AAA35913|]
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guanine nucleotide exchange factor [Homo sapiens]

Protein Classification

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List of domain hits

 Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 776-1015 2.80e-81

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


:

Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 266.43  E-value: 2.80e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    776 LLTLHPIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSR 854
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    855 IIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSI--NPPCVPFF 930
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    931 GIYLTNILKTEEGNPEVLKrhgKELINFSKRRKVAEITGEIQQYQNQPYCLRVESDIKRFFENLNPmgnsmEKEFTDYLF 1010
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLE---GNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                 ....*
gi 306778   1011 NKSLE 1015
Cdd:cd00155  233 ELSLE 237
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 439-545 6.09e-55

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269963  Cd Length: 109  Bit Score: 186.41  E-value: 6.09e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    439 QCCNEFIMEGTLTRVGA---KHERHIFLFDGLMICCKSNHGQPRLPGASnAEYRLKEKFFMRKVQINDKDDTNEYKHAFE 515
Cdd:cd01261    1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGGPK-PEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 306778    516 IILKDENSVIFSAKSAEEKNNWMAALISLQ 545
Cdd:cd01261   80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-95 2.27e-46

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


:

Pssm-ID: 467039  Cd Length: 78  Bit Score: 160.50  E-value: 2.27e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 306778     18 KWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIE 95
Cdd:cd22914    1 KWRGLLVPALKKVQKQVHPTLVAKEDALEYIEELILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 597-741 8.70e-42

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


:

Pssm-ID: 214571  Cd Length: 127  Bit Score: 149.41  E-value: 8.70e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       597 GIPIIKAGTVIKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTeadriaiengdqplsaelk 675
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 306778       676 RFRKEYIQPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVRGKAMKKWVESITKIIQRKK 741
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 104-177 4.59e-39

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


:

Pssm-ID: 467040  Cd Length: 75  Bit Score: 139.68  E-value: 4.59e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 306778    104 SLPVEKIHPLL-KEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFH 177
Cdd:cd22915    1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLFG 75
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 204-389 1.68e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


:

Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 133.58  E-value: 1.68e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       204 LVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDegSPHPLVGSCF 283
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       284 EDLAEelAFDPYESYARDilrpgfHDRFLSQLSK----PGAALYLQSIGEGFKEAVqYVLPRLLLAPVYHCLHYFELLKQ 359
Cdd:smart00325   79 LKLEE--FFKIYSEYCSN------HPDALELLKKlkknPRFQKFLKEIESSPQCRR-LTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 306778       360 LEEKSE-DQEDKECLKQAITALLNVQSGMEK 389
Cdd:smart00325  150 LLKHTPeDHEDREDLKKALKAIKELANQVNE 180
PTZ00449 super family cl33186
104 kDa microneme/rhoptry antigen; Provisional
 1018-1319 2.10e-06

104 kDa microneme/rhoptry antigen; Provisional


The actual alignment was detected with superfamily member PTZ00449:

Pssm-ID: 185628 [Multi-domain]  Cd Length: 943  Bit Score: 52.38  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1018 PRNPKPlPRFPKKYSYPlKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAPNSPRTPLTP-PPASGAS 1096
Cdd:PTZ00449  588 PKDPEE-PKKPKRPRSA-QRPTRPKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPkPPKSPKP 665

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1097 SttdvcsvFDSDHSSPFHSSndtvfiqvtlphgprsaSVSSISLTKGTDEVPVPPPVPPRRRPESAPAESSPSkimskhL 1176
Cdd:PTZ00449  666 P-------FDPKFKEKFYDD-----------------YLDAAAKSKETKTTVVLDESFESILKETLPETPGTP------F 715

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1177 DSPPAIPPRQPTSKAYSprysisdrtsisdppesppllppREPVRTPDVFSSSPLHLQPPPLGKKSdhgnaFFpnspspf 1256
Cdd:PTZ00449  716 TTPRPLPPKLPRDEEFP-----------------------FEPIGDPDAEQPDDIEFFTPPEEERT-----FF------- 760

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1257 tppppqtpspHGTRRHLPSPPLTQEV----DLHSIAGPPVPPRQ---STSQHIPKLPpktykreHTHPSM 1319
Cdd:PTZ00449  761 ----------HETPADTPLPDILAEEfkeeDIHAETGEPDEAMKrpdSPSEHEDKPP-------GDHPSL 813
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 776-1015 2.80e-81

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 266.43  E-value: 2.80e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    776 LLTLHPIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSR 854
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    855 IIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSI--NPPCVPFF 930
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    931 GIYLTNILKTEEGNPEVLKrhgKELINFSKRRKVAEITGEIQQYQNQPYCLRVESDIKRFFENLNPmgnsmEKEFTDYLF 1010
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLE---GNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                 ....*
gi 306778   1011 NKSLE 1015
Cdd:cd00155  233 ELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
776-1020 1.65e-80

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 264.49  E-value: 1.65e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       776 LLTLHPIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSP-NLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSR 854
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       855 IIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSIN-PPCVPFFG 931
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELlsPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       932 IYLTNILKTEEGNPEVLKrhgKELINFSKRRKVAEITGEIQQYQNQPYCLRVE-SDIKRFFENLnpMGNSMEKEftdYLF 1010
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLE---NGLVNFEKRRQIAEILREIRQLQSQPYNLRPNrSDIQSLLQQL--LDHLDEEE---ELY 232

                           250
                    ....*....|
gi 306778      1011 NKSLEIEPRN 1020
Cdd:smart00147  233 QLSLKIEPRV 242
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 783-962 7.23e-69

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 229.02  E-value: 7.23e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      783 EIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSRIIEILQVF 862
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      863 QELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSINPPCVPFFGIYLTNILKT 940
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLmsPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170       180
                   ....*....|....*....|..
gi 306778      941 EEGNPevlKRHGKELINFSKRR 962
Cdd:pfam00617  161 EEGNP---DFLEGGLINFEKRR 179
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 439-545 6.09e-55

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 186.41  E-value: 6.09e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    439 QCCNEFIMEGTLTRVGA---KHERHIFLFDGLMICCKSNHGQPRLPGASnAEYRLKEKFFMRKVQINDKDDTNEYKHAFE 515
Cdd:cd01261    1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGGPK-PEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 306778    516 IILKDENSVIFSAKSAEEKNNWMAALISLQ 545
Cdd:cd01261   80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-95 2.27e-46

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


Pssm-ID: 467039  Cd Length: 78  Bit Score: 160.50  E-value: 2.27e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 306778     18 KWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIE 95
Cdd:cd22914    1 KWRGLLVPALKKVQKQVHPTLVAKEDALEYIEELILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 597-741 8.70e-42

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 149.41  E-value: 8.70e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       597 GIPIIKAGTVIKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTeadriaiengdqplsaelk 675
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 306778       676 RFRKEYIQPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVRGKAMKKWVESITKIIQRKK 741
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 104-177 4.59e-39

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


Pssm-ID: 467040  Cd Length: 75  Bit Score: 139.68  E-value: 4.59e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 306778    104 SLPVEKIHPLL-KEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFH 177
Cdd:cd22915    1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLFG 75
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 204-389 1.68e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 133.58  E-value: 1.68e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       204 LVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDegSPHPLVGSCF 283
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       284 EDLAEelAFDPYESYARDilrpgfHDRFLSQLSK----PGAALYLQSIGEGFKEAVqYVLPRLLLAPVYHCLHYFELLKQ 359
Cdd:smart00325   79 LKLEE--FFKIYSEYCSN------HPDALELLKKlkknPRFQKFLKEIESSPQCRR-LTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 306778       360 LEEKSE-DQEDKECLKQAITALLNVQSGMEK 389
Cdd:smart00325  150 LLKHTPeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 201-388 2.08e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 133.19  E-value: 2.08e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    201 YYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDegSPHPLVG 280
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    281 SCFEDLAEelAFDPYESYARDilrpgfHDRFLSQLSKP-GAALYLQSIGEGFKEAVQ-YVLPRLLLAPVYHCLHYFELLK 358
Cdd:cd00160   79 DVFLKLAP--FFKIYSEYCSN------HPDALELLKKLkKFNKFFQEFLEKAESECGrLKLESLLLKPVQRLTKYPLLLK 150

                        170       180       190
                 ....*....|....*....|....*....|.
gi 306778    359 QLEEKSED-QEDKECLKQAITALLNVQSGME 388
Cdd:cd00160  151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 605-739 6.45e-35

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 129.45  E-value: 6.45e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    605 TVIKLIERLTYHM-YADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEAdriaiengdqplsaelKRFRKEYIQ 683
Cdd:cd06224    1 TLEALIEHLTSTFdMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPPENLEY----------------NDWDKKKSK 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 306778    684 PVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVR--GKAMKKWVESITKIIQR 739
Cdd:cd06224   65 PIRLRVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVqeGALLQELKKLLRKLLKL 122
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 600-717 2.32e-33

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 124.34  E-value: 2.32e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      600 IIKAGTVIKLIERLTYHMYA-DPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADRIAIEngdqplsaelkrfR 678
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRIMlDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWIS-------------K 67

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 306778      679 KEYiqPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEF 717
Cdd:pfam00618   68 KTL--PIRIRVLSVLRHWVENYFSDFNDDPVLLSRLEKF 104
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 213-383 1.09e-16

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 79.27  E-value: 1.09e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      213 RQYIRELNLIIKVFREPFVSNSKLfSANDVENIFSRIVDIHELSVKLLghIEdtvEMTDEGSPHPLVGSCFEDLAEElaF 292
Cdd:pfam00621   10 RSYVRDLEILVEVFLPPNSKPLSE-SEEEIKTIFSNIEEIYELHRQLL--LE---ELLKEWISIQRIGDIFLKFAPG--F 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      293 DPYESYARDilrpgfHDRFLSQLSK-----PGAALYLQSIgEGFKEAVQYVLPRLLLAPVYHCLHYFELLKQLEEK-SED 366
Cdd:pfam00621   82 KVYSTYCSN------YPKALKLLKKllkknPKFRAFLEEL-EANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHtPPD 154

                          170
                   ....*....|....*..
gi 306778      367 QEDKECLKQAITALLNV 383
Cdd:pfam00621  155 HPDYEDLKKALEAIKEV 171
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 444-546 5.68e-16

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 74.89  E-value: 5.68e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       444 FIMEGTLTRVGAK-----HERHIFLFDGLMICCKSNHgqprlpgaSNAEYRLKEKFFMRKVQINDKDDT--NEYKHAFEI 516
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLYYKSKK--------DKKSYKPKGSIDLSGCTVREAPDPdsSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 306778       517 ILKDENSVIFSAKSAEEKNNWMAALISLQY 546
Cdd:smart00233   73 KTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 445-546 3.03e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 58.73  E-value: 3.03e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      445 IMEGTLTRVGAK-----HERHIFLFDGLMICCKsnhgqprlPGASNAEYRLKEKFFMRKVQIND--KDDTNEYKHAFEII 517
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswKKRYFVLFDGSLLYYK--------DDKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELR 73

                           90       100       110
                   ....*....|....*....|....*....|..
gi 306778      518 LKD---ENSVIFSAKSAEEKNNWMAALISLQY 546
Cdd:pfam00169   74 TGErtgKRTYLLQAESEEERKDWIKAIQSAIR 105
H2A smart00414
Histone 2A;
97-176 1.20e-07

Histone 2A;


Pssm-ID: 197711  Cd Length: 106  Bit Score: 51.18  E-value: 1.20e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778        97 RKRRNPLSLPVEKIHPLLKE-VLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDM 175
Cdd:smart00414    2 RSARAGLQFPVGRIHRLLRKgTYAKRVGAGAPVYLAAVLEYLTAEVLELAGNAARDNKKRRITPRHLQLAIRNDEELNKL 81


                    .
gi 306778       176 F 176
Cdd:smart00414   82 L 82
HTA1 COG5262
Histone H2A [Chromatin structure and dynamics];
84-177 1.60e-07

Histone H2A [Chromatin structure and dynamics];


Pssm-ID: 227587 [Multi-domain]  Cd Length: 132  Bit Score: 51.79  E-value: 1.60e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778     84 KWAIADAQSAIEKRKRRNPLSLPVEKIHPLLKEVLG-YKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDI 162
Cdd:COG5262    6 KGGKAADARVSQSRSAKAGLIFPVGRVKRLLKKGNYrMRIGAGAPVYLAAVLEYLAAEILELAGNAARDNKKKRIIPRHL 85

                         90
                 ....*....|....*
gi 306778    163 KVAMCADKVLMDMFH 177
Cdd:COG5262   86 QLAIRNDEELNKLLG 100
PTZ00449 PTZ00449
104 kDa microneme/rhoptry antigen; Provisional
 1018-1319 2.10e-06

104 kDa microneme/rhoptry antigen; Provisional


Pssm-ID: 185628 [Multi-domain]  Cd Length: 943  Bit Score: 52.38  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1018 PRNPKPlPRFPKKYSYPlKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAPNSPRTPLTP-PPASGAS 1096
Cdd:PTZ00449  588 PKDPEE-PKKPKRPRSA-QRPTRPKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPkPPKSPKP 665

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1097 SttdvcsvFDSDHSSPFHSSndtvfiqvtlphgprsaSVSSISLTKGTDEVPVPPPVPPRRRPESAPAESSPSkimskhL 1176
Cdd:PTZ00449  666 P-------FDPKFKEKFYDD-----------------YLDAAAKSKETKTTVVLDESFESILKETLPETPGTP------F 715

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1177 DSPPAIPPRQPTSKAYSprysisdrtsisdppesppllppREPVRTPDVFSSSPLHLQPPPLGKKSdhgnaFFpnspspf 1256
Cdd:PTZ00449  716 TTPRPLPPKLPRDEEFP-----------------------FEPIGDPDAEQPDDIEFFTPPEEERT-----FF------- 760

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1257 tppppqtpspHGTRRHLPSPPLTQEV----DLHSIAGPPVPPRQ---STSQHIPKLPpktykreHTHPSM 1319
Cdd:PTZ00449  761 ----------HETPADTPLPDILAEEfkeeDIHAETGEPDEAMKrpdSPSEHEDKPP-------GDHPSL 813
PLN00154 PLN00154
histone H2A; Provisional
 97-172 2.45e-06

histone H2A; Provisional


Pssm-ID: 177756  Cd Length: 136  Bit Score: 48.40  E-value: 2.45e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 306778      97 RKRRNPLSLPVEKIHPLLKEVL--GYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVL 172
Cdd:PLN00154   31 RSSRAGLQFPVGRIHRQLKQRVsaHGRVGATAAVYTAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEEL 108
 
Name Accession Description Interval E-value
RasGEF cd00155
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ...
 776-1015 2.80e-81

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.


Pssm-ID: 238087 [Multi-domain]  Cd Length: 237  Bit Score: 266.43  E-value: 2.80e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    776 LLTLHPIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEI-NSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSR 854
Cdd:cd00155    1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNIhLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    855 IIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSI--NPPCVPFF 930
Cdd:cd00155   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELvdPSRNFKNYRKLLKSVgpNPPCVPFL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    931 GIYLTNILKTEEGNPEVLKrhgKELINFSKRRKVAEITGEIQQYQNQPYCLRVESDIKRFFENLNPmgnsmEKEFTDYLF 1010
Cdd:cd00155  161 GVYLKDLTFLHEGNPDFLE---GNLVNFEKRRKIAEILREIRQLQSNSYELNRDEDILAFLWKLLE-----LILNEDELY 232


                 ....*
gi 306778   1011 NKSLE 1015
Cdd:cd00155  233 ELSLE 237
RasGEF smart00147
Guanine nucleotide exchange factor for Ras-like small GTPases;
776-1020 1.65e-80

Guanine nucleotide exchange factor for Ras-like small GTPases;


Pssm-ID: 214539  Cd Length: 242  Bit Score: 264.49  E-value: 1.65e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       776 LLTLHPIEIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSP-NLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSR 854
Cdd:smart00147    1 LLLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlNLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSK 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       855 IIEILQVFQELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSIN-PPCVPFFG 931
Cdd:smart00147   81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELlsPERNYKNYREALSSCNlPPCIPFLG 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       932 IYLTNILKTEEGNPEVLKrhgKELINFSKRRKVAEITGEIQQYQNQPYCLRVE-SDIKRFFENLnpMGNSMEKEftdYLF 1010
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLE---NGLVNFEKRRQIAEILREIRQLQSQPYNLRPNrSDIQSLLQQL--LDHLDEEE---ELY 232

                           250
                    ....*....|
gi 306778      1011 NKSLEIEPRN 1020
Cdd:smart00147  233 QLSLKIEPRV 242
RasGEF pfam00617
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.
 783-962 7.23e-69

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.


Pssm-ID: 459872  Cd Length: 179  Bit Score: 229.02  E-value: 7.23e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      783 EIARQLTLLESDLYRAVQPSELVGSVWTKEDKEINSPNLLKMIRHTTNLTLWFEKCIVETENLEERVAVVSRIIEILQVF 862
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWSKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      863 QELNNFNGVLEVVSAMNSSPVYRLDHTFEQIPSRQKKILEEAHEL--SEDHYKKYLAKLRSINPPCVPFFGIYLTNILKT 940
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLmsPSRNFKNYREALSSASPPCIPFLGLYLTDLTFI 160

                          170       180
                   ....*....|....*....|..
gi 306778      941 EEGNPevlKRHGKELINFSKRR 962
Cdd:pfam00617  161 EEGNP---DFLEGGLINFEKRR 179
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
 439-545 6.09e-55

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 186.41  E-value: 6.09e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    439 QCCNEFIMEGTLTRVGA---KHERHIFLFDGLMICCKSNHGQPRLPGASnAEYRLKEKFFMRKVQINDKDDTNEYKHAFE 515
Cdd:cd01261    1 QCCNEFIMEGTLGKVGSgkrKTERHAFLFDGLLLLCKSNRRRTSTGGPK-PEYRLKEKFFIRKVEINDLEDTEELKNAFE 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 306778    516 IILKDENSVIFSAKSAEEKNNWMAALISLQ 545
Cdd:cd01261   80 IVPRDQPSVILFAKSAEEKNNWMAALVMLN 109
HFD_SOS1_rpt1 cd22914
first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 18-95 2.27e-46

first histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the first repeat.


Pssm-ID: 467039  Cd Length: 78  Bit Score: 160.50  E-value: 2.27e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 306778     18 KWRGLLVPALKKVQGQVHPTLESNDDALQYVEELILQLLNMLCQAQPRSASDVEERVQKSFPHPIDKWAIADAQSAIE 95
Cdd:cd22914    1 KWRGLLVPALKKVQKQVHPTLVAKEDALEYIEELILQLLNMLCAAQPHSVQDVEERVQKTFPHPIDKWAIADAQAALE 78
RasGEFN smart00229
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine ...
 597-741 8.70e-42

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).


Pssm-ID: 214571  Cd Length: 127  Bit Score: 149.41  E-value: 8.70e-42
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       597 GIPIIKAGTVIKLIERLTYHMY-ADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTeadriaiengdqplsaelk 675
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDkADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPPESW------------------- 61

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 306778       676 RFRKEYIQPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVRGKAMKKWVESITKIIQRKK 741
Cdd:smart00229   62 VEEKVNPRRVKNRVLNILRTWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGLVTSLLNLLRRLS 127
HFD_SOS1_rpt2 cd22915
second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; ...
 104-177 4.59e-39

second histone-fold domain found in son of sevenless homolog 1 (SOS-1) and similar proteins; SOS-1 is a guanine nucleotide exchange factor for Ras that binds to GRB2. It promotes the exchange of Ras-bound GDP by GTP. It is a catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac, by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity. SOS-1 contains tandem histone folds at the N-terminal region. The model corresponds to the second repeat.


Pssm-ID: 467040  Cd Length: 75  Bit Score: 139.68  E-value: 4.59e-39
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 306778    104 SLPVEKIHPLL-KEVLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDMFH 177
Cdd:cd22915    1 LFPVDKIHPLLkKDLLVYKVDPQVSLYLVAVLEYIAADILKLAGNYVRNIRHYEITSQDIKVAMCADKVLMDLFG 75
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
 204-389 1.68e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 133.58  E-value: 1.68e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       204 LVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDegSPHPLVGSCF 283
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWD--DSVERIGDVF 78

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       284 EDLAEelAFDPYESYARDilrpgfHDRFLSQLSK----PGAALYLQSIGEGFKEAVqYVLPRLLLAPVYHCLHYFELLKQ 359
Cdd:smart00325   79 LKLEE--FFKIYSEYCSN------HPDALELLKKlkknPRFQKFLKEIESSPQCRR-LTLESLLLKPVQRLTKYPLLLKE 149

                           170       180       190
                    ....*....|....*....|....*....|.
gi 306778       360 LEEKSE-DQEDKECLKQAITALLNVQSGMEK 389
Cdd:smart00325  150 LLKHTPeDHEDREDLKKALKAIKELANQVNE 180
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
 201-388 2.08e-35

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 133.19  E-value: 2.08e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    201 YYDLVKAFMAEIRQYIRELNLIIKVFREPFVSNSKLFSANDVENIFSRIVDIHELSVKLLGHIEDTVEMTDegSPHPLVG 280
Cdd:cd00160    1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWD--KSGPRIG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    281 SCFEDLAEelAFDPYESYARDilrpgfHDRFLSQLSKP-GAALYLQSIGEGFKEAVQ-YVLPRLLLAPVYHCLHYFELLK 358
Cdd:cd00160   79 DVFLKLAP--FFKIYSEYCSN------HPDALELLKKLkKFNKFFQEFLEKAESECGrLKLESLLLKPVQRLTKYPLLLK 150

                        170       180       190
                 ....*....|....*....|....*....|.
gi 306778    359 QLEEKSED-QEDKECLKQAITALLNVQSGME 388
Cdd:cd00160  151 ELLKHTPDgHEDREDLKKALEAIKEVASQVN 181
REM cd06224
Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also ...
 605-739 6.45e-35

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.


Pssm-ID: 100121  Cd Length: 122  Bit Score: 129.45  E-value: 6.45e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    605 TVIKLIERLTYHM-YADPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEAdriaiengdqplsaelKRFRKEYIQ 683
Cdd:cd06224    1 TLEALIEHLTSTFdMPDPSFVSTFLLTYRSFTTPTELLEKLIERYEIAPPENLEY----------------NDWDKKKSK 64

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 306778    684 PVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEFIGTVR--GKAMKKWVESITKIIQR 739
Cdd:cd06224   65 PIRLRVLNVLRTWVENYPYDFFDDEELLELLEEFLNRLVqeGALLQELKKLLRKLLKL 122
RasGEF_N pfam00618
RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small ...
 600-717 2.32e-33

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.


Pssm-ID: 459873  Cd Length: 104  Bit Score: 124.34  E-value: 2.32e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      600 IIKAGTVIKLIERLTYHMYA-DPNFVRTFLTTYRSFCKPQELLSLIIERFEIPEPEPTEADRIAIEngdqplsaelkrfR 678
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRIMlDDSFLSTFLLTYRSFTTPAELLELLIERYNIPPPLDLSSDSYWIS-------------K 67

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 306778      679 KEYiqPVQLRVLNVCRHWVEHHFYDFERDAYLLQRMEEF 717
Cdd:pfam00618   68 KTL--PIRIRVLSVLRHWVENYFSDFNDDPVLLSRLEKF 104
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
 419-542 3.57e-20

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 88.09  E-value: 3.57e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    419 IKKMNEIQKNIDGWEGKDIGQCCNEFIMEGTLTRVGAKH--ERHIFLFDGLMICCKSNHGqprlpGASNAEYrlKEKFFM 496
Cdd:cd01224    4 LEKLAAWQSTVEGWEGEDLSDRSSELIHSGELTKISAGRaqERTFFLFDHQLVYCKKDLL-----RRKNYIY--KGRIDT 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 306778    497 RKVQIND----KDDTNEY--KHAFEIILKDENSV-IFSAKSAEEKNNWMAALI 542
Cdd:cd01224   77 DNMEIEDlpdgKDDESGVtvKNAWKIYNASKNKWyVLCAKSAEEKQRWLEAFA 129
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
 213-383 1.09e-16

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 79.27  E-value: 1.09e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      213 RQYIRELNLIIKVFREPFVSNSKLfSANDVENIFSRIVDIHELSVKLLghIEdtvEMTDEGSPHPLVGSCFEDLAEElaF 292
Cdd:pfam00621   10 RSYVRDLEILVEVFLPPNSKPLSE-SEEEIKTIFSNIEEIYELHRQLL--LE---ELLKEWISIQRIGDIFLKFAPG--F 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      293 DPYESYARDilrpgfHDRFLSQLSK-----PGAALYLQSIgEGFKEAVQYVLPRLLLAPVYHCLHYFELLKQLEEK-SED 366
Cdd:pfam00621   82 KVYSTYCSN------YPKALKLLKKllkknPKFRAFLEEL-EANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHtPPD 154

                          170
                   ....*....|....*..
gi 306778      367 QEDKECLKQAITALLNV 383
Cdd:pfam00621  155 HPDYEDLKKALEAIKEV 171
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 444-546 5.68e-16

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 74.89  E-value: 5.68e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778       444 FIMEGTLTRVGAK-----HERHIFLFDGLMICCKSNHgqprlpgaSNAEYRLKEKFFMRKVQINDKDDT--NEYKHAFEI 516
Cdd:smart00233    1 VIKEGWLYKKSGGgkkswKKRYFVLFNSTLLYYKSKK--------DKKSYKPKGSIDLSGCTVREAPDPdsSKKPHCFEI 72

                            90       100       110
                    ....*....|....*....|....*....|
gi 306778       517 ILKDENSVIFSAKSAEEKNNWMAALISLQY 546
Cdd:smart00233   73 KTSDRKTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 445-546 3.03e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 58.73  E-value: 3.03e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778      445 IMEGTLTRVGAK-----HERHIFLFDGLMICCKsnhgqprlPGASNAEYRLKEKFFMRKVQIND--KDDTNEYKHAFEII 517
Cdd:pfam00169    2 VKEGWLLKKGGGkkkswKKRYFVLFDGSLLYYK--------DDKSGKSKEPKGSISLSGCEVVEvvASDSPKRKFCFELR 73

                           90       100       110
                   ....*....|....*....|....*....|..
gi 306778      518 LKD---ENSVIFSAKSAEEKNNWMAALISLQY 546
Cdd:pfam00169   74 TGErtgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
 411-538 3.16e-10

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 59.67  E-value: 3.16e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    411 QMKGKQLAIKKMNEIQKNIDGWEGKDIgQCCNEFIMEGTLTRVGAKHERHIFLFDGLMICCKSNhgqprlpgaSNAEYRL 490
Cdd:cd13243   20 DMKRKHEHAVRVQEIQSLLDGWEGPEL-TTYGDLVLEGTFRMAGAKNERLLFLFDKMLLITKKR---------EDGILQY 89

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 306778    491 KEKFFMRKVQIN---DKDDTneykhAFEIILKDE--NSVIFSAKSAEEKNNWM 538
Cdd:cd13243   90 KTHIMCSNLMLSesiPKEPL-----SFQVLPFDNpkLQYTLQAKNQEQKRLWT 137
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 446-541 6.41e-10

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 57.17  E-value: 6.41e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    446 MEGTLTRVGAK-----HERHIFLFDGLMICCKSNHGQPrlpgasnaeYRLKEKFFMRKVQINDKDDTNEYKHAFEIILKD 520
Cdd:cd00821    1 KEGYLLKRGGGglkswKKRWFVLFEGVLLYYKSKKDSS---------YKPKGSIPLSGILEVEEVSPKERPHCFELVTPD 71

                         90       100
                 ....*....|....*....|.
gi 306778    521 ENSVIFSAKSAEEKNNWMAAL 541
Cdd:cd00821   72 GRTYYLQADSEEERQEWLKAL 92
HFD_H2A cd00074
histone-fold domain found in histone H2A and similar proteins; Histone H2A is the core ...
 95-177 5.80e-09

histone-fold domain found in histone H2A and similar proteins; Histone H2A is the core component of the nucleosome, which wraps and compacts DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.


Pssm-ID: 467020  Cd Length: 89  Bit Score: 54.46  E-value: 5.80e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778     95 EKRKRRNPLSLPVEKIHPLLKEvlgYKIDHQVS----VYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADK 170
Cdd:cd00074    1 QSRSKRAGLQFPVGRIHRLLKK---GTYAKRVGagapVYLAAVLEYLTAEILELAGNAARDNKKKRITPRHIQLAIRNDE 77


                 ....*..
gi 306778    171 VLMDMFH 177
Cdd:cd00074   78 ELNKLFK 84
H2A smart00414
Histone 2A;
97-176 1.20e-07

Histone 2A;


Pssm-ID: 197711  Cd Length: 106  Bit Score: 51.18  E-value: 1.20e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778        97 RKRRNPLSLPVEKIHPLLKE-VLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVLMDM 175
Cdd:smart00414    2 RSARAGLQFPVGRIHRLLRKgTYAKRVGAGAPVYLAAVLEYLTAEVLELAGNAARDNKKRRITPRHLQLAIRNDEELNKL 81


                    .
gi 306778       176 F 176
Cdd:smart00414   82 L 82
HTA1 COG5262
Histone H2A [Chromatin structure and dynamics];
84-177 1.60e-07

Histone H2A [Chromatin structure and dynamics];


Pssm-ID: 227587 [Multi-domain]  Cd Length: 132  Bit Score: 51.79  E-value: 1.60e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778     84 KWAIADAQSAIEKRKRRNPLSLPVEKIHPLLKEVLG-YKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDI 162
Cdd:COG5262    6 KGGKAADARVSQSRSAKAGLIFPVGRVKRLLKKGNYrMRIGAGAPVYLAAVLEYLAAEILELAGNAARDNKKKRIIPRHL 85

                         90
                 ....*....|....*
gi 306778    163 KVAMCADKVLMDMFH 177
Cdd:COG5262   86 QLAIRNDEELNKLLG 100
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
 443-541 3.27e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 50.35  E-value: 3.27e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    443 EFIMEGTLTRVGAK--HERHIFLF-DGLMICCksnhgqprlPGASNAEYRLKEKF---FMrKVQINDKDdtnEYKHAFEI 516
Cdd:cd13389   13 KLIKEGELMKVSRKemQPRYFFLFnDCLLYTT---------PVQSSGMLKLNNELplsGM-KVKLPEDE---EYSNEFQI 79

                         90       100
                 ....*....|....*....|....*
gi 306778    517 IlKDENSVIFSAKSAEEKNNWMAAL 541
Cdd:cd13389   80 I-STKRSFTLIASSEEERDEWVKAL 103
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
 444-541 3.58e-07

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 50.33  E-value: 3.58e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    444 FIMEGTLTRVGAK--HERHIFLFDGLMICCKSNHGQPRlpgasnaeYRLKEKFFMRKVQINDKDDTNEYKHAFEIILKDE 521
Cdd:cd01218   30 LVGEGVLTKVCRKkpKPRQFFLFNDILVYGSIVINKKK--------YNKQRIIPLEDVKIEDLEDTGELKNGWQIISPKK 101

                         90       100
                 ....*....|....*....|
gi 306778    522 NSVIFsAKSAEEKNNWMAAL 541
Cdd:cd01218  102 SFVVY-AATATEKSEWMDHI 120
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
 447-541 6.58e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 48.64  E-value: 6.58e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    447 EGTLTRVGAKH----ERHIFLFDGLMICCksnhgQPRLPGASnAEYRLKEKFFMRKVQINDKDDTNeYKHAFEIILKdEN 522
Cdd:cd13328    2 EGQILKLSAKNgtpqPRYLFLFNDMLLYC-----VPKLSLVG-QKFSVRNRLDVAGMKVREPVNEN-YPHTFKISGK-ER 73

                         90
                 ....*....|....*....
gi 306778    523 SVIFSAKSAEEKNNWMAAL 541
Cdd:cd13328   74 SLELQASSAEEKDEWIQAI 92
PTZ00449 PTZ00449
104 kDa microneme/rhoptry antigen; Provisional
 1018-1319 2.10e-06

104 kDa microneme/rhoptry antigen; Provisional


Pssm-ID: 185628 [Multi-domain]  Cd Length: 943  Bit Score: 52.38  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1018 PRNPKPlPRFPKKYSYPlKSPGVRPSNPRPGTMRHPTPLQQEPRKISYSRIPESETESTASAPNSPRTPLTP-PPASGAS 1096
Cdd:PTZ00449  588 PKDPEE-PKKPKRPRSA-QRPTRPKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPkPPKSPKP 665

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1097 SttdvcsvFDSDHSSPFHSSndtvfiqvtlphgprsaSVSSISLTKGTDEVPVPPPVPPRRRPESAPAESSPSkimskhL 1176
Cdd:PTZ00449  666 P-------FDPKFKEKFYDD-----------------YLDAAAKSKETKTTVVLDESFESILKETLPETPGTP------F 715

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1177 DSPPAIPPRQPTSKAYSprysisdrtsisdppesppllppREPVRTPDVFSSSPLHLQPPPLGKKSdhgnaFFpnspspf 1256
Cdd:PTZ00449  716 TTPRPLPPKLPRDEEFP-----------------------FEPIGDPDAEQPDDIEFFTPPEEERT-----FF------- 760

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1257 tppppqtpspHGTRRHLPSPPLTQEV----DLHSIAGPPVPPRQ---STSQHIPKLPpktykreHTHPSM 1319
Cdd:PTZ00449  761 ----------HETPADTPLPDILAEEfkeeDIHAETGEPDEAMKrpdSPSEHEDKPP-------GDHPSL 813
PLN00154 PLN00154
histone H2A; Provisional
 97-172 2.45e-06

histone H2A; Provisional


Pssm-ID: 177756  Cd Length: 136  Bit Score: 48.40  E-value: 2.45e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 306778      97 RKRRNPLSLPVEKIHPLLKEVL--GYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVL 172
Cdd:PLN00154   31 RSSRAGLQFPVGRIHRQLKQRVsaHGRVGATAAVYTAAILEYLTAEVLELAGNASKDLKVKRITPRHLQLAIRGDEEL 108
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
 452-541 4.50e-06

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 46.16  E-value: 4.50e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    452 RVGAKHERHIFLFDGLMICCksnhgQPRL-PGASnaEYRLKEKFFMRKVQINDKDDTnEYKHAFEIILKdENSVIFSAKS 530
Cdd:cd13388   13 RNGDTQERYLFLFNDMLLYC-----SPRLrLIGQ--KYKVRARFDVDGMQVLEGDNL-ETPHTFYVRGK-QRSLELQAST 83

                         90
                 ....*....|.
gi 306778    531 AEEKNNWMAAL 541
Cdd:cd13388   84 QEEKAEWVDAI 94
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
 455-541 5.32e-05

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269930  Cd Length: 127  Bit Score: 44.16  E-value: 5.32e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    455 AKHERHIFLFDGLMICCKSNHGqprlpgasnAEYRLKEKFFMRKVQIND------KDDTNEYKHAFEIILKDENSVI-FS 527
Cdd:cd01223   34 KKKDRYAFLFDKVLLICKSLRG---------DQYEYKEIINLSEYRIEDdpsrrtLKRDKRWSYQFLLVHKQGKTAYtLY 104

                         90
                 ....*....|....
gi 306778    528 AKSAEEKNNWMAAL 541
Cdd:cd01223  105 AKTEELKKKWMEAI 118
PLN00153 PLN00153
histone H2A; Provisional
 97-172 8.04e-05

histone H2A; Provisional


Pssm-ID: 165721 [Multi-domain]  Cd Length: 129  Bit Score: 43.94  E-value: 8.04e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 306778      97 RKRRNPLSLPVEKIHPLLKE-VLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVL 172
Cdd:PLN00153   17 RSAKAGLQFPVGRIARYLKKgKYAERIGAGAPVYLAAVLEYLTAEVLELAGNAARDNKKNRIVPRHIQLAIRNDEEL 93
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
 457-548 8.83e-05

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270059  Cd Length: 125  Bit Score: 43.69  E-value: 8.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    457 HERHIFLFDGLMICCKsnhgQPRLPGASNAEYRLKEKFFMRKVQINDKDDTNEykHAFEIILKDENSV---IFSAKSAEE 533
Cdd:cd13239   37 HHRHVFLFKNCVVICK----PKRDSRTDTVTYVFKNKMKLSDIDVKDTVEGDD--RSFGLWHEHRGSVrkyTLQARSAII 110

                         90
                 ....*....|....*
gi 306778    534 KNNWMAALISLQYRS 548
Cdd:cd13239  111 KSSWLKDLRDLQQRL 125
PH_Scd1 cd13246
Shape and Conjugation Deficiency 1 Pleckstrin homology (PH) domain; Fission yeast Scd1 is an ...
 424-545 6.84e-04

Shape and Conjugation Deficiency 1 Pleckstrin homology (PH) domain; Fission yeast Scd1 is an exchange factor for Cdc42 and an effector of Ras1, the homolog of the human H-Ras. Scd2/Bem1 mediates Cdc42 activation by binding to Scd1/Cdc24 and to Cdc42. Ras1 regulates Scd1/Cdc24/Ral1, which is a putative guanine nucleotide exchange factor for Cdc42, a member of the Rho family of Ras-like proteins. Cdc42 then activates the Shk1/Orb2 protein kinase. Scd1 interacts with Klp5 and Klp6 kinesins to mediate cytokinesis. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270066  Cd Length: 148  Bit Score: 41.46  E-value: 6.84e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    424 EIQKNIDGWEGKDIGQCcNEFIMEGTLTRVGAKHER--HIFLFDGLMICCK------------SNHGQPRLPGASNAEYR 489
Cdd:cd13246   12 DLKARVEDWKGHSLDSF-GELLLHDTFTVRKDDSEReyHVYLFERILLCCKeekkkkkkkgskSKSSSSSKKKKGKGPLQ 90

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    490 LKEKFFMRKV-QINDKDDTNEYkhAFEIILKDEN---SVIFSAKSAEEKNNWMAALISLQ 545
Cdd:cd13246   91 LKGRIYIRNItDVTSSSKPGEY--SLQITWKGDDeleSFILKFRNEEQLKQWESTINRLI 148
PLN00157 PLN00157
histone H2A; Provisional
 97-172 1.44e-03

histone H2A; Provisional


Pssm-ID: 177758  Cd Length: 132  Bit Score: 40.22  E-value: 1.44e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 306778      97 RKRRNPLSLPVEKIHPLLKE-VLGYKIDHQVSVYIVAVLEYISADILKLVGNYVRNIRHYEITKQDIKVAMCADKVL 172
Cdd:PLN00157   19 RSAKAGLQFPVGRIARYLKAgKYATRVGAGAPVYLAAVLEYLAAEVLELAGNAARDNKKSRIVPRHIQLAVRNDEEL 95
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1017-1325 1.48e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 43.39  E-value: 1.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1017 EPRNPKPLPRFPKKYSYPLKSPGVRPSNPRPGTMRHPTplqqePRKISYSRIPESETEST--ASAPNSPRTPLTPPPASG 1094
Cdd:PHA03247 2620 DTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPA-----PGRVSRPRRARRLGRAAqaSSPPQRPRRRAARPTVGS 2694

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1095 ASSTTDVCSVFDSDHSSPFHSSNDTvfiqvTLPHGPRSASVSSISLTKG--------TDEVPVPPPVPPRRRPESAPAES 1166
Cdd:PHA03247 2695 LTSLADPPPPPPTPEPAPHALVSAT-----PLPPGPAAARQASPALPAApappavpaGPATPGGPARPARPPTTAGPPAP 2769

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1167 SPSKimskhldSPPAIPPRQPTSKAYSP-RYSISDRTSISDPPESPPLLPPREPVRTPDVFSSSPL-----------HLQ 1234
Cdd:PHA03247 2770 APPA-------APAAGPPRRLTRPAVASlSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLppptsaqptapPPP 2842

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1235 PPPLGKKSDHGNAF-----FPNSPSPFTPPPPQTPSPHGTRRHLPSPPLTQEVDlhSIAGPPV---PPRQSTSQHIPKLP 1306
Cdd:PHA03247 2843 PGPPPPSLPLGGSVapggdVRRRPPSRSPAAKPAAPARPPVRRLARPAVSRSTE--SFALPPDqpeRPPQPQAPPPPQPQ 2920

                         330
                  ....*....|....*....
gi 306778    1307 PKTYKREHTHPSMHRDGPP 1325
Cdd:PHA03247 2921 PQPPPPPQPQPPPPPPPRP 2939
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 448-545 1.93e-03

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 39.19  E-value: 1.93e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    448 GTLTRVGAKHERHIFLFDGlmicckSNHGQPRLpgasnaEYRLKEKFFMRKVQ------------INDKDDTnEYKHAFE 515
Cdd:cd01257    7 GYLKKLKTMRKRYFVLRAE------SHGGPARL------EYYENEKKFRRNAEpkrviplsscfnINKRADA-KHKHLIA 73

                         90       100       110
                 ....*....|....*....|....*....|
gi 306778    516 IILKDENSVIfSAKSAEEKNNWMAALISLQ 545
Cdd:cd01257   74 LYTKDECFGL-VAESEEEQDEWYQALLELQ 102
PH_RalBD_exo84 cd01226
Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 ...
 444-541 1.95e-03

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269933  Cd Length: 115  Bit Score: 39.56  E-value: 1.95e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    444 FIMEGTLTRVGAKHER-----HIFLF-DGLMICCKSNHGQprlpgaSNAEYRLKEKFFMRKVQINDKDDTNEYKHAFEII 517
Cdd:cd01226    8 LLHEGDLLELDPDDYKpiqkvHLFLLnDVLLIASWLPNRR------GPVRYKFQALYPLEDLAVVNVKDLGPVKNAFKLL 81

                         90       100
                 ....*....|....*....|....
gi 306778    518 LKDEnSVIFSAKSAEEKNNWMAAL 541
Cdd:cd01226   82 TFPE-TRVFQCENAKIKKEWLEKF 104
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
 444-538 3.69e-03

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 38.41  E-value: 3.69e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    444 FIMEGTLTRVGAKH----ERHIFLFDGLMICCKSnhgQPRLPGasnAEYRLKEKFFMRKVQINDKDDTNeYKHAFEIILK 519
Cdd:cd13387    1 LIKEGHIQKLSAKNgtaqDRYLYLFNSMVLYCVP---KLRLMG---QKFSVREKIDIAGMQVQEIVKQN-VPHTFTITGK 73

                         90
                 ....*....|....*....
gi 306778    520 dENSVIFSAKSAEEKNNWM 538
Cdd:cd13387   74 -KRSLELQARTEEEKKEWI 91
PHA03247 PHA03247
large tegument protein UL36; Provisional
 1018-1307 5.24e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 41.46  E-value: 5.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1018 PRNPKPLPRFPKKySYPLKSPGVRPSnprpgtmrhptplqqEPRKISYSRIPESETESTasAPNSPRTPLTPPPASGASS 1097
Cdd:PHA03247 2554 PLPPAAPPAAPDR-SVPPPRPAPRPS---------------EPAVTSRARRPDAPPQSA--RPRAPVDDRGDPRGPAPPS 2615

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1098 ttdvcsvfdsdhSSPfhssndtvfiQVTLPHGPRSASVSSISLTKGTDEVPVPPPVPPRRRPESAPAESSPSKIMSKHLD 1177
Cdd:PHA03247 2616 ------------PLP----------PDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRA 2673

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 306778    1178 SPPAIPPRQPTSKAYSPrySISDRTSISDPPesppllpprEPVRTPDVFSSSPLHLQPPPLGKKSDhGNAFFPNSPSPFT 1257
Cdd:PHA03247 2674 AQASSPPQRPRRRAARP--TVGSLTSLADPP---------PPPPTPEPAPHALVSATPLPPGPAAA-RQASPALPAAPAP 2741

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 306778    1258 PPPPQTPSPHGTRRHLPSPPLTqevdlhsiAGP--PVPPRQSTSQHIPKLPP 1307
Cdd:PHA03247 2742 PAVPAGPATPGGPARPARPPTT--------AGPpaPAPPAAPAAGPPRRLTR 2785
PH_SKIP cd13309
SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called ...
 512-541 8.86e-03

SifA and kinesin-interacting protein Pleckstrin homology (PH) domain; SKIP (also called PLEKHM2/Pleckstrin homology domain-containing family M member 2) is a soluble cytosolic protein that contains a RUN domain and a PH domain separated by a unstructured linker region. SKIP is a target of the Salmonella effector protein SifA and the SifA-SKIP complex regulates kinesin-1 on the bacterial vacuole. The PH domain of SKIP binds to the N-terminal region of SifA while the N-terminus of SKIP is proposed to bind the TPR domain of the kinesin light chain. The opposite side of the SKIP PH domain is proposed to bind phosphoinositides. TSifA, SKIP, SseJ, and RhoA family GTPases are also thought to promote host membrane tubulation. Recently, it was shown that the lysosomal GTPase Arl8 binds to the kinesin-1 linker SKIP and that both are required for the normal intracellular distribution of lysosomes. Interestingly, two kinesin light chain binding motifs (WD) in SKIP have now been identified to match a consensus sequence for a kinesin light chain binding site found in several proteins including calsyntenin-1/alcadein, caytaxin, and vaccinia virus A36. SKIP has also been shown to interact with Rab1A. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270119  Cd Length: 103  Bit Score: 37.36  E-value: 8.86e-03
                         10        20        30
                 ....*....|....*....|....*....|
gi 306778    512 HAFEIILKDENSVIFSAKSAEEKNNWMAAL 541
Cdd:cd13309   67 HTFELILTDRSSLELAAPDEYEASEWLQSL 96
 
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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