D-mannose binding lectin; These proteins include mannose-specific lectins from plants as well as bacteriocins from bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  79 TIVWVANRESPLggDASTYLLKIL-DGNLILHDNisatrkshtegtsrrspqkisegnllFHETVWSTGVNSSMSKDVQA 157
Cdd:pfam01453   1 TVVWVANRDNPI--NDSSGVLTISnDGNLVLLNG--------------------------SNSVVWSTNNSSSSANNTVA 52

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1039017920 158 VLFDSGNLVLRDGPNSSAaVLWQSFDHPSDTWLPGGKIRL-----GSQLFTSW 205
Cdd:pfam01453  53 QLLDSGNLVLSDDSNSGN-VLWQSFDHPTDTLLPGMKLGWnkrtgLNRRLTSW 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 543 LGEGGFGPVYKGKLPNGMEVAIKRLSKKSSQ-GLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDGL 621
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCAaSKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDR 80

                  ...
gi 1039017920 622 LFG 624
Cdd:cd14066    81 LHC 83

D-mannose binding lectin; These proteins include mannose-specific lectins from plants as well as bacteriocins from bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  79 TIVWVANRESPLggDASTYLLKIL-DGNLILHDNisatrkshtegtsrrspqkisegnllFHETVWSTGVNSSMSKDVQA 157
Cdd:pfam01453   1 TVVWVANRDNPI--NDSSGVLTISnDGNLVLLNG--------------------------SNSVVWSTNNSSSSANNTVA 52

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1039017920 158 VLFDSGNLVLRDGPNSSAaVLWQSFDHPSDTWLPGGKIRL-----GSQLFTSW 205
Cdd:pfam01453  53 QLLDSGNLVLSDDSNSGN-VLWQSFDHPTDTLLPGMKLGWnkrtgLNRRLTSW 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 543 LGEGGFGPVYKGKLPNGMEVAIKRLSKKSSQ-GLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDGL 621
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCAaSKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDR 80

                  ...
gi 1039017920 622 LFG 624
Cdd:cd14066    81 LHC 83

Bulb-type mannose-specific lectin;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920   33 NQPLSGFETIVSSGDIFELGLFTPTPdtydhRNYYIGMWYRHvSPQTIVWVANRESPLGGDAStylLKIL-DGNLILHDN 111
Cdd:smart00108   1 SNTLSSGQTLVSGNSLFELGFFTLIM-----QNDYNLILYKS-SSRTVVWVANRDNPVSDSCT---LTLQsDGNLVLYDG 71

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039017920  112 ISAtrkshtegtsrrspqkisegnllfheTVWSTGVNSSMSkDVQAVLFDSGNLVLRDgpnSSAAVLWQSFDH 184
Cdd:smart00108  72 DGR--------------------------VVWSSNTTGANG-NYVLVLLDDGNLVIYD---SDGNFLWQSFDY 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  540 KKKLGEGGFGPVYKGKL-----PNGMEVAIKRLSK-KSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:smart00219   4 GKKLGEGAFGEVYKGKLkgkggKKKVEVAVKTLKEdASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYM 83

                   ....*....
gi 1039017920  614 SNKSLDGLL 622
Cdd:smart00219  84 EGGDLLSYL 92

Plant PAN/APPLE-like domain; present in plant S-receptor protein kinases and secreted glycoproteins. PAN/APPLE domains fulfill diverse biological functions by mediating protein-protein or protein-carbohydrate interactions. S-receptor protein kinases and S-locus glycoproteins are involved in sporophytic self-incompatibility response in Brassica, one of probably many molecular mechanisms, by which hermaphrodite flowering plants avoid self-fertilization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 364 TYLHCYKRN--DEFLPIENMKLatdPTTASVLTSGTFRTCASRCVADCSCQAYA--NDGNKCLVWTKDAFNLQQLDANkG 439
Cdd:cd01098     1 TPLNCGGDGstDGFLKLPDVKL---PDNASAITAISLEECREACLSNCSCTAYAynNGSGGCLLWNGLLNNLRSLSSG-G 76

                  ....*...
gi 1039017920 440 HTFFLRLA 447
Cdd:cd01098    77 GTLYLRLA 84

leucine-rich repeat receptor-like protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 535 NSFSRKKKlgeggfGPVYKGK-LPNGMEVAIKRLSKKSSQGLTEFKNevvlIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:PLN00113  696 NVISRGKK------GASYKGKsIKNGMQFVVKEINDVNSIPSSEIAD----MGKLQHPNIVKLIGLCRSEKGAYLIHEYI 765

                          90
                  ....*....|.
gi 1039017920 614 SNKSLDGLLFG 624
Cdd:PLN00113  766 EGKNLSEVLRN 776

D-mannose binding lectin; These proteins include mannose-specific lectins from plants as well as bacteriocins from bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  79 TIVWVANRESPLggDASTYLLKIL-DGNLILHDNisatrkshtegtsrrspqkisegnllFHETVWSTGVNSSMSKDVQA 157
Cdd:pfam01453   1 TVVWVANRDNPI--NDSSGVLTISnDGNLVLLNG--------------------------SNSVVWSTNNSSSSANNTVA 52

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1039017920 158 VLFDSGNLVLRDGPNSSAaVLWQSFDHPSDTWLPGGKIRL-----GSQLFTSW 205
Cdd:pfam01453  53 QLLDSGNLVLSDDSNSGN-VLWQSFDHPTDTLLPGMKLGWnkrtgLNRRLTSW 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 543 LGEGGFGPVYKGKLPNGMEVAIKRLSKKSSQ-GLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDGL 621
Cdd:cd14066     1 IGSGGFGTVYKGVLENGTVVAVKRLNEMNCAaSKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDR 80

                  ...
gi 1039017920 622 LFG 624
Cdd:cd14066    81 LHC 83

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 543 LGEGGFGPVYKGKLPNGMEVAIKRLSKKSSQGLT-EFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDGL 621
Cdd:cd14664     1 IGRGGAGTVYKGVMPNGTLVAVKRLKGEGTQGGDhGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGEL 80

                  ...
gi 1039017920 622 LFG 624
Cdd:cd14664    81 LHS 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 541 KKLGEGGFGPVYKGKL----PNGMEVAIKRL-SKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSN 615
Cdd:cd00192     1 KKLGEGAFGEVYKGKLkggdGKTVDVAVKTLkEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80

                  ....*..
gi 1039017920 616 KSLDGLL 622
Cdd:cd00192    81 GDLLDFL 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  540 KKKLGEGGFGPVYKGKL-----PNGMEVAIKRLSK-KSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:smart00219   4 GKKLGEGAFGEVYKGKLkgkggKKKVEVAVKTLKEdASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYM 83

                   ....*....
gi 1039017920  614 SNKSLDGLL 622
Cdd:smart00219  84 EGGDLLSYL 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920  540 KKKLGEGGFGPVYKGKL-----PNGMEVAIKRLSK-KSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:smart00221   4 GKKLGEGAFGEVYKGTLkgkgdGKEVEVAVKTLKEdASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYM 83

                   ....*....
gi 1039017920  614 SNKSLDGLL 622
Cdd:smart00221  84 PGGDLLDYL 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 537 FSRKKKLGEGGFGPVYKGKL-----PNGMEVAIKRLSKK-SSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIY 610
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLkgegeNTKIKVAVKTLKEGaDEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVT 80

                  ....*....
gi 1039017920 611 EYMSNKSLD 619
Cdd:pfam07714  81 EYMPGGDLL 89

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 537 FSRKKKLGEGGFGPVYKGKL-PNGMEVAIKRLsKKSSQGLTEFKN---EVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEY 612
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHrDTGKIVAIKKI-KKEKIKKKKDKNilrEIKILKKLNHPNIVRLYDAFEDKDNLYLVLEY 79

                          90
                  ....*....|
gi 1039017920 613 MSNKSLDGLL 622
Cdd:pfam00069  80 VEGGSLFDLL 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 543 LGEGGFGPVYKGK-LPNGMEVAIKRLSKKSSQG-LTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDG 620
Cdd:cd00180     1 LGKGSFGKVYKARdKETGKKVAVKVIPKEKLKKlLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKD 80

                  ..
gi 1039017920 621 LL 622
Cdd:cd00180    81 LL 82

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 540 KKKLGEGGFGPVYKGKLPN------GMEVAIKRLSKKSSQGLTE-FKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEY 612
Cdd:cd05049    10 KRELGEGAFGKVFLGECYNlepeqdKMLVAVKTLKDASSPDARKdFEREAELLTNLQHENIVKFYGVCTEGDPLLMVFEY 89

                          90
                  ....*....|
gi 1039017920 613 MSNKSLDGLL 622
Cdd:cd05049    90 MEHGDLNKFL 99

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 537 FSRKKKLGEGGFGPVYKGK-LPNGMEVAIKRLSKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSN 615
Cdd:cd05122     2 FEILEKIGKGGFGVVYKARhKKTGQIVAIKKINLESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81

                  ....*..
gi 1039017920 616 KSLDGLL 622
Cdd:cd05122    82 GSLKDLL 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 541 KKLGEGGFGPVYKG-KLPNGMEVAIKRLS--KKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKS 617
Cdd:cd06627     6 DLIGRGAFGSVYKGlNLNTGEFVAIKQISleKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGS 85

                  ....*....
gi 1039017920 618 LDGLL--FG 624
Cdd:cd06627    86 LASIIkkFG 94

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 536 SFSRKKKLGEGGFGPVYKGK-LPNGMEVAIK--RLSKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEY 612
Cdd:cd06606     1 RWKKGELLGKGSFGSVYLALnLDTGELMAVKevELSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEY 80

                          90
                  ....*....|....
gi 1039017920 613 MSNKSLDGLL--FG 624
Cdd:cd06606    81 VPGGSLASLLkkFG 94

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 540 KKKLGEGGFGPVYKGKLPN------GMEVAIKRLSKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:cd05092    10 KWELGEGAFGKVFLAECHNllpeqdKMLVAVKALKEATESARQDFQREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYM 89

                  ....*....
gi 1039017920 614 SNKSLDGLL 622
Cdd:cd05092    90 RHGDLNRFL 98

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 545 EGGFGPVYKGKlPNGMEVAIKRLSKK--SSQGLTE--FKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKSLDG 620
Cdd:cd14157     3 EGTFADIYKGY-RHGKQYVIKRLKETecESPKSTErfFQTEVQICFRCCHPNILPLLGFCVESDCHCLIYPYMPNGSLQD 81

                  ..
gi 1039017920 621 LL 622
Cdd:cd14157    82 RL 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 540 KKKLGEGGFGPVYKGKLPN------GMEVAIKRLSKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:cd05094    10 KRELGEGAFGKVFLAECYNlsptkdKMLVAVKTLKDPTLAARKDFQREAELLTNLQHDHIVKFYGVCGDGDPLIMVFEYM 89

                  ....*....
gi 1039017920 614 SNKSLDGLL 622
Cdd:cd05094    90 KHGDLNKFL 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 535 NSFSRKKKLGEGGFGPVYKGKLPNGMEVAIKRLsKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMS 614
Cdd:cd05068     8 KSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTL-KPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPIYIITELMK 86

                  ....
gi 1039017920 615 NKSL 618
Cdd:cd05068    87 HGSL 90

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 537 FSRKKKLGEGGFGPVYKGK-LPNGMEVAIK--RLSKKSSQGLtefKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYM 613
Cdd:cd06614     2 YKNLEKIGEGASGEVYKATdRATGKEVAIKkmRLRKQNKELI---INEILIMKECKHPNIVDYYDSYLVGDELWVVMEYM 78

                  ....*
gi 1039017920 614 SNKSL 618
Cdd:cd06614    79 DGGSL 83

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 541 KKLGEGGFGPVYKGK-LPNGMEVAIKRLSKK--SSQGLTE-FKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNK 616
Cdd:cd14007     6 KPLGKGKFGNVYLAReKKSGFIVALKVISKSqlQKSGLEHqLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNG 85

                  ..
gi 1039017920 617 SL 618
Cdd:cd14007    86 EL 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 538 SRKKKLGEGGFGPVYKGKLPNGMEVAIKRLsKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNKS 617
Cdd:cd05112     7 TFVQEIGSGQFGLVHLGYWLNKDKVAIKTI-REGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGC 85

                  ....*
gi 1039017920 618 LDGLL 622
Cdd:cd05112    86 LSDYL 90

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 541 KKLGEGGFGPVYKGK-LPNGMEVAIKRLSK---KSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVEGDEKLLIYEYMSNK 616
Cdd:COG0515    13 RLLGRGGMGVVYLARdLRLGRPVALKVLRPelaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVMEYVEGE 92

                  ....*.
gi 1039017920 617 SLDGLL 622
Cdd:COG0515    93 SLADLL 98

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039017920 529 DIMVATNSFSRKKKLGEGGFGPVYKGKL--PNG--MEVAIK--RLSKKSSQGLTEFKNEVVLIIKLQHKNLVRLLGYCVE 602
Cdd:cd14204     1 DVMIDRNLLSLGKVLGEGEFGSVMEGELqqPDGtnHKVAVKtmKLDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLE 80