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 485836935   81 VRQLKRVGEGAVKRVFLSEWKEH------KVA---LSQLTSLEMKDDFLHGLQMLKSLQGTHVVTLLGYCEDDNT--MLT 149
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGEgentkiKVAvktLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPlyIVT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 485836935  150 EYHPLGSLSNLeetlnLSKYQNVNTWQHRLELA------MDYVSIINYLH 193
Cdd:pfam07714  81 EYMPGGDLLDF-----LRKHKRKLTLKDLLSMAlqiakgMEYLESKNFVH 125

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 485836935  91 AVKRvflsewkehkvaLSQLTSLEMKDDFLHGLQMLKSLQGTHVVTLLGYC--EDDNTMLTEYHPLGSLsnlEETLNLSK 168
Cdd:cd14066   21 AVKR------------LNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCleSDEKLLVYEYMPNGSL---EDRLHCHK 85

                         90       100
                 ....*....|....*....|....*..
gi 485836935 169 YQNVNTWQHRLELAMDYVSIINYLHHS 195
Cdd:cd14066   86 GSPPLPWPQRLKIAKGIARGLEYLHEE 112

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 485836935   81 VRQLKRVGEGAVKRVFLSEWKEH------KVA---LSQLTSLEMKDDFLHGLQMLKSLQGTHVVTLLGYCEDDNT--MLT 149
Cdd:pfam07714   1 LTLGEKLGEGAFGEVYKGTLKGEgentkiKVAvktLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPlyIVT 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 485836935  150 EYHPLGSLSNLeetlnLSKYQNVNTWQHRLELA------MDYVSIINYLH 193
Cdd:pfam07714  81 EYMPGGDLLDF-----LRKHKRKLTLKDLLSMAlqiakgMEYLESKNFVH 125

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 485836935    84 LKRVGEGAVKRVFLSEWKEHK------VALSQL---TSLEMKDDFLHGLQMLKSLQGTHVVTLLGYCEDDN--TMLTEYH 152
Cdd:smart00221   4 GKKLGEGAFGEVYKGTLKGKGdgkeveVAVKTLkedASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEplMIVMEYM 83

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 485836935   153 PLGSLSNLeetlnLSKYQNVN-TWQHRLELA------MDYVSIINYLH 193
Cdd:smart00221  84 PGGDLLDY-----LRKNRPKElSLSDLLSFAlqiargMEYLESKNFIH 126

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  86 RVGEGAVKRVFLSEWKEHKVALSQLTSL------EMKDDFLHGLQMLKSLQGTHVVTLLGY-CEDDNTMLT-EYHPLGSL 157
Cdd:cd14158   22 KLGEGGFGVVFKGYINDKNVAVKKLAAMvdisteDLTKQFEQEIQVMAKCQHENLVELLGYsCDGPQLCLVyTYMPNGSL 101

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 485836935 158 ----SNLEETLNLSkyqnvntWQHRLELAMDYVSIINYLH 193
Cdd:cd14158  102 ldrlACLNDTPPLS-------WHMRCKIAQGTANGINYLH 134

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  90 GAVKRVFLSEWKEHKVALSQLTSLE-----MKDDFLHGLQMLKSLQGTHVVTLLGYCEDDNTMLT-EYHPLGSLSNLEET 163
Cdd:cd05116    9 GTVKKGYYQMKKVVKTVAVKILKNEandpaLKDELLREANVMQQLDNPYIVRMIGICEAESWMLVmEMAELGPLNKFLQK 88

                         90       100       110
                 ....*....|....*....|....*....|
gi 485836935 164 LNLSKYQNVNTWQHRLELAMDYVSIINYLH 193
Cdd:cd05116   89 NRHVTEKNITELVHQVSMGMKYLEESNFVH 118

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  85 KRVGEGAVKRVFLSEWKEHKVALSQLTSLEMKDDF----LHGLQMLkslqgtHVVTLLGYCEDDNT---------MLTEY 151
Cdd:cd14056    1 KTIGKGRYGEVWLGKYRGEKVAVKIFSSRDEDSWFreteIYQTVML------RHENILGFIAADIKstgswtqlwLITEY 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 485836935 152 HPLGSLSN--LEETLNLSKYqnvntwqhrLELAMDYVSIINYLHHSPVGTR 200
Cdd:cd14056   75 HEHGSLYDylQRNTLDTEEA---------LRLAYSAASGLAHLHTEIVGTQ 116

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 485836935  84 LKRV-GEGAVKRVFLSEWKE-------HKVALSQL---TSLEMKDDFLHGLQMLKSLQGTHVVTLLGYCEDDNT--MLTE 150
Cdd:cd05049    9 LKRElGEGAFGKVFLGECYNlepeqdkMLVAVKTLkdaSSPDARKDFEREAELLTNLQHENIVKFYGVCTEGDPllMVFE 88

                         90
                 ....*....|
gi 485836935 151 YHPLGSLSNL 160
Cdd:cd05049   89 YMEHGDLNKF 98

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  79 TEVRQLKRVGEGAVKRVFLSEWKEHK------VALSQL---TSLEMKDDFLHGLQMLKSLQGTHVVTLLGYCEDDNTML- 148
Cdd:cd05057    7 TELEKGKVLGSGAFGTVYKGVWIPEGekvkipVAIKVLreeTGPKANEEILDEAYVMASVDHPHLVRLLGICLSSQVQLi 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935 149 TEYHPLGSLSNL--EETLNLSKYQNVNtWQHRLELAMDYVSIINYLHhspvgtRVMCDSNDLPKTLSQYLLTsNFSiLAN 226
Cdd:cd05057   87 TQLMPLGCLLDYvrNHRDNIGSQLLLN-WCVQIAKGMSYLEEKRLVH------RDLAARNVLVKTPNHVKIT-DFG-LAK 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 485836935 227 DLDALPLVNHSSG-------MLVKCGHrelHGDFVAPEQLWPYG 263
Cdd:cd05057  158 LLDVDEKEYHAEGgkvpikwMALESIQ---YRIYTHKSDVWSYG 198

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  80 EVRQLKRVGEGAVKRVFLSEWKEH-KVALSQLTSLEM-KDDFLHGLQMLKSLQGTHVVTLLGYCEDDNTM--LTEYHPLG 155
Cdd:cd05059    5 ELTFLKELGSGQFGVVHLGKWRGKiDVAIKMIKEGSMsEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIfiVTEYMANG 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 485836935 156 SLSNLeetlnLSKYQNVNTWQHRLEL------AMDYVSIINYLH 193
Cdd:cd05059   85 CLLNY-----LRERRGKFQTEQLLEMckdvceAMEYLESNGFIH 123

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  87 VGEGAVKRVFLSEWKEHKVALSQLTSLEMKDD--FLHGLQMLKSLQGTHVVTLLGYC-EDDNTMLTEYHPLGSLSNLeet 163
Cdd:cd05037   15 IYDGILREVGDGRVQEVEVLLKVLDSDHRDISesFFETASLMSQISHKHLVKLYGVCvADENIMVQEYVRYGPLDKY--- 91

                         90       100       110
                 ....*....|....*....|....*....|
gi 485836935 164 lnLSKYQNvNTWQH-RLELAMDYVSIINYL 192
Cdd:cd05037   92 --LRRMGN-NVPLSwKLQVAKQLASALHYL 118

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  81 VRQLKRVGEGAVKRVflseWKEH-----------KVALSQL---TSLEMKDDFLHGLQMLKSLQGTHVVTLLGYC--EDD 144
Cdd:cd05048    7 VRFLEELGEGAFGKV----YKGEllgpsseesaiSVAIKTLkenASPKTQQDFRREAELMSDLQHPNIVCLLGVCtkEQP 82

                         90
                 ....*....|...
gi 485836935 145 NTMLTEYHPLGSL 157
Cdd:cd05048   83 QCMLFEYMAHGDL 95

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 485836935  75 EELRTEVRQLKRVGEGAVKRVFLSEWKEH-KVALSQLTSLEM--KDDFLHGLQMLKSLQGTHVVTLLGYCEDDNT--MLT 149
Cdd:cd05148    2 ERPREEFTLERKLGSGYFGEVWEGLWKNRvRVAIKILKSDDLlkQQDFQKEVQALKRLRHKHLISLFAVCSVGEPvyIIT 81

                 ....*...
gi 485836935 150 EYHPLGSL 157
Cdd:cd05148   82 ELMEKGSL 89