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 1720423200   34 SDLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELF 113
Cdd:cd14206    131 SDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELF 210

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVRQQHVKLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 179
Cdd:cd14206    211 EFGAQPYRHLSDEEVLTFVVREQQMKLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 276

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   34 SDLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELF 113
Cdd:cd14206    131 SDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELF 210

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVRQQHVKLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 179
Cdd:cd14206    211 EFGAQPYRHLSDEEVLTFVVREQQMKLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 276

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 1720423200    35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYlTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:smart00221  128 DLAARNCLVGENLVVKISDFGLSRDLYDDDYY-KVKGGKLPIRWMAPESL--KEGKF-----TSKSDVWSFGVLLWEIFT 199

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720423200   115 FGAQPYRHLSDEEVLAFVVRQQhvKLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQL 177
Cdd:smart00221  200 LGEEPYPGMSNAEVLEYLKKGY--RLPKP----PNCpPELYKLMLQCWAEdPEDRPTFSELVEIL 258

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   34 SDLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELF 113
Cdd:cd14206    131 SDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELF 210

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVRQQHVKLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 179
Cdd:cd14206    211 EFGAQPYRHLSDEEVLTFVVREQQMKLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 276

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   34 SDLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELF 113
Cdd:cd05087    126 SDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVTADQLWVPLRWIAPELVDEVHGNLLVVDQTKQSNVWSLGVTIWELF 205

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVRQQHVKLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 179
Cdd:cd05087    206 ELGNQPYRHYSDRQVLTYTVREQQLKLPKPQLKLSLAERWYEVMQFCWLQPEQRPTAEEVHLLLSY 271

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 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd00192    130 DLAARNCLVGEDLVVKISDFGLSRDIYDDDYYRKKTGGKLPIRWMAPESL--KDGIF-----TSKSDVWSFGVLLWEIFT 202

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  115 FGAQPYRHLSDEEVLAFVVRQQhvKLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQLT 178
Cdd:cd00192    203 LGATPYPGLSNEEVLEYLRKGY--RLPKP----ENCpDELYELMLSCWQLdPEDRPTFSELVERLE 262

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 1720423200    35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYlTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:smart00221  128 DLAARNCLVGENLVVKISDFGLSRDLYDDDYY-KVKGGKLPIRWMAPESL--KEGKF-----TSKSDVWSFGVLLWEIFT 199

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720423200   115 FGAQPYRHLSDEEVLAFVVRQQhvKLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQL 177
Cdd:smart00221  200 LGEEPYPGMSNAEVLEYLKKGY--RLPKP----PNCpPELYKLMLQCWAEdPEDRPTFSELVEIL 258

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGElhGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05032    144 DLAARNCMVAEDLTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKD--GVF-----TTKSDVWSFGVVLWEMAT 216

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720423200  115 FGAQPYRHLSDEEVLAFVVRQQHvklarprLKLPYA--DYWYDILQSCWR-PPAQRPSASDL 173
Cdd:cd05032    217 LAEQPYQGLSNEEVLKFVIDGGH-------LDLPENcpDKLLELMRMCWQyNPKMRPTFLEI 271

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTS----DLTVRIGDYGLAHSNYKEDYYLTP-ERLwVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTL 109
Cdd:cd05044    131 DLAARNCLVSSkdyrERVVKIGDFGLARDIYKNDYYRKEgEGL-LPVRWMAPESL--VDGVF-----TTQSDVWAFGVLM 202

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720423200  110 WELFEFGAQPYRHLSDEEVLAFVvrQQHVKLARPRlKLPyaDYWYDILQSCWR-PPAQRPSASDLQLQL 177
Cdd:cd05044    203 WEILTLGQQPYPARNNLEVLHFV--RAGGRLDQPD-NCP--DDLYELMLRCWStDPEERPSFARILEQL 266

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTpERLWVPLRWAAPELLGElhgsfvlVDQSRESNVWSLGVTLWELFE 114
Cdd:cd05046    142 DLAARNCLVSSQREVKVSLLSLSKDVYNSEYYKL-RNALIPLRWLAPEAVQE-------DDFSTKSDVWSFGVLMWEVFT 213

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720423200  115 FGAQPYRHLSDEEVLAfvvrqqhvKLARPRLKLPYAD----YWYDILQSCWRP-PAQRPSASDL 173
Cdd:cd05046    214 QGELPFYGLSDEEVLN--------RLQAGKLELPVPEgcpsRLYKLMTRCWAVnPKDRPSFSEL 269

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05050    155 DLATRNCLVGENMVVKIADFGLSRNIYSADYYKASENDAIPIRWMPPESI--FYNRY-----TTESDVWAYGVVLWEIFS 227

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720423200  115 FGAQPYRHLSDEEVLAFvVRQQHVkLARPR---LKLpyadywYDILQSCW-RPPAQRPSASDL 173
Cdd:cd05050    228 YGMQPYYGMAHEEVIYY-VRDGNV-LSCPDncpLEL------YNLMRLCWsKLPSDRPSFASI 282

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHS-NYKEDYY-LTPERLWvPLRWAAPELLGelHGSFvlvdqSRESNVWSLGVTLWEL 112
Cdd:cd05060    120 DLAARNVLLVNRHQAKISDFGMSRAlGAGSDYYrATTAGRW-PLKWYAPECIN--YGKF-----SSKSDVWSYGVTLWEA 191

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  113 FEFGAQPYRHLSDEEVLAFVvrQQHVKLARPRlKLPyaDYWYDILQSCWR-PPAQRPSASDLQLQL 177
Cdd:cd05060    192 FSYGAKPYGEMKGPEVIAML--ESGERLPRPE-ECP--QEIYSIMLSCWKyRPEDRPTFSELESTF 252

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05090    149 DLAARNILVGEQLHVKISDLGLSREIYSSDYYRVQNKSLLPIRWMPPEAI--MYGKF-----SSDSDIWSFGVVLWEIFS 221

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720423200  115 FGAQPYRHLSDEEVLAFVVRQQHVKLAR---PRLklpyadywYDILQSCWRP-PAQRPSASDLQLQL 177
Cdd:cd05090    222 FGLQPYYGFSNQEVIEMVRKRQLLPCSEdcpPRM--------YSLMTECWQEiPSRRPRFKDIHARL 280

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGElhGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05061    144 DLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKD--GVF-----TTSSDMWSFGVVLWEITS 216

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720423200  115 FGAQPYRHLSDEEVLAFVVRQQHvkLARPRlKLPyaDYWYDILQSCWR-PPAQRPS 169
Cdd:cd05061    217 LAEQPYQGLSNEQVLKFVMDGGY--LDQPD-NCP--ERVTDLMRMCWQfNPKMRPT 267

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHS-NYKEDYYLTPERLWVPLRWAAPELLGElhGSFvlvdqSRESNVWSLGVTLWELF 113
Cdd:cd05038    134 DLAARNILVESEDLVKISDFGLAKVlPEDKEYYYVKEPGESPIFWYAPECLRE--SRF-----SSASDVWSFGVTLYELF 206

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720423200  114 EFG-------AQPYRHLSDEEVLAFVVRQQHVKLARPRLKLPYA--DYWYDILQSCWRP-PAQRPSASDLQLQLTYLL 181
Cdd:cd05038    207 TYGdpsqsppALFLRMIGIAQGQMIVTRLLELLKSGERLPRPPScpDEVYDLMKECWEYePQDRPSFSDLILIIDRLR 284

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPEllgelhgSFVLVDQSRESNVWSLGVTLWELFE 114
Cdd:cd05093    145 DLATRNCLVGENLLVKIGDFGMSRDVYSTDYYRVGGHTMLPIRWMPPE-------SIMYRKFTTESDVWSLGVVLWEIFT 217

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720423200  115 FGAQPYRHLSDEEVLAFVVrqQHVKLARPRlklPYADYWYDILQSCW-RPPAQRPSASDLQLQLTYL 180
Cdd:cd05093    218 YGKQPWYQLSNNEVIECIT--QGRVLQRPR---TCPKEVYDLMLGCWqREPHMRLNIKEIHSLLQNL 279

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05091    150 DLATRNVLVFDKLNVKISDLGLFREVYAADYYKLMGNSLLPIRWMSPEAI--MYGKF-----SIDSDIWSYGVVLWEVFS 222

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720423200  115 FGAQPYRHLSDEEVlafvvrqqhVKLARPRLKLPYAD----YWYDILQSCWRP-PAQRPSASDLQLQL 177
Cdd:cd05091    223 YGLQPYCGYSNQDV---------IEMIRNRQVLPCPDdcpaWVYTLMLECWNEfPSRRPRFKDIHSRL 281

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGE-LHgsfvlvdqSRESNVWSLGVTLWELF 113
Cdd:cd05074    148 DLAARNCMLNENMTVCVADFGLSKKIYSGDYYRQGCASKLPVKWLALESLADnVY--------TTHSDVWAFGVTMWEIM 219

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVRQQhvklarpRLKLPY--ADYWYDILQSCWRP-PAQRPSASDLQLQLTYLL 181
Cdd:cd05074    220 TRGQTPYAGVENSEIYNYLIKGN-------RLKQPPdcLEDVYELMCQCWSPePKCRPSFQHLRDQLELIW 283

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLahSNYK-EDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELF 113
Cdd:cd05113    125 DLAARNCLVNDQGVVKVSDFGL--SRYVlDDEYTSSVGSKFPVRWSPPEVL--MYSKF-----SSKSDVWAFGVLMWEVY 195

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFVVrqQHVKLARPRLKlpyADYWYDILQSCWRP-PAQRPSASDL 173
Cdd:cd05113    196 SLGKMPYERFTNSETVEHVS--QGLRLYRPHLA---SEKVYTIMYSCWHEkADERPTFKIL 251

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLGE-LHGSfvlvdqsrESNVWSLGVTLWELF 113
Cdd:cd05035    138 DLAARNCMLDENMTVCVADFGLSRKIYSGDYYRQGRISKMPVKWIALESLADnVYTS--------KSDVWSFGVTMWEIA 209

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720423200  114 EFGAQPYRHLSDEEVLAFvVRQQHvklarpRLKLPY--ADYWYDILQSCWR-PPAQRPSASDLQLQLTYLL 181
Cdd:cd05035    210 TRGQTPYPGVENHEIYDY-LRNGN------RLKQPEdcLDEVYFLMYFCWTvDPKDRPTFTKLREVLENIL 273

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423200   35 DLALRNCLLTSDLTVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFE 114
Cdd:cd05097    154 DLATRNCLVGNHYTIKIADFGMSRNLYSGDYYRIQGRAVLPIRWMAWESI--LLGKF-----TTASDVWAFGVTLWEMFT 226

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720423200  115 F-GAQPYRHLSDEEVLA-----FVVRQQHVKLARPRLklpYADYWYDILQSCW-RPPAQRPS 169
Cdd:cd05097    227 LcKEQPYSLLSDEQVIEntgefFRNQGRQIYLSQTPL---CPSPVFKLMMRCWsRDIKDRPT 285