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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd14206     76 MEFCQLGDLKRYLRAQRKADGMTPDLPTRDLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSH 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQHV 160
Cdd:cd14206    156 NNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQM 235

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 201
Cdd:cd14206    236 KLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd14206     76 MEFCQLGDLKRYLRAQRKADGMTPDLPTRDLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSH 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQHV 160
Cdd:cd14206    156 NNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQM 235

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 201
Cdd:cd14206    236 KLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 276

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 1720423198    1 MEFCQLGDLKRYLRAQRPPegmspeLPPRDLrtLQrMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:pfam07714   80 TEYMPGGDLLDFLRKHKRK------LTLKDL--LS-MALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSR 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQhv 160
Cdd:pfam07714  151 DIYDDDYYRKRGGGKLPIKWMAPESL--KDGKF-----TSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGY-- 221

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQL 199
Cdd:pfam07714  222 RLPQP----ENCpDELYDLMKQCWAYdPEDRPTFSELVEDL 258

NIMA-related protein kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198    1 MEFCQLGDLKRYLRaQRPPEgmspELPPRDlrtlQRMGL---EIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYG 77
Cdd:PTZ00267   144 MEYGSGGDLNKQIK-QRLKE----HLPFQE----YEVGLlfyQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFG 214

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   78 ------------LAHSNYKEDYYLTPErLWVPLRWaapellgelhgsfvlvdqSRESNVWSLGVTLWELFEFgAQPYRHL 145
Cdd:PTZ00267   215 fskqysdsvsldVASSFCGTPYYLAPE-LWERKRY------------------SKKADMWSLGVILYELLTL-HRPFKGP 274

                          170
                   ....*....|
gi 1720423198  146 SDEEVLAFVV 155
Cdd:PTZ00267   275 SQREIMQQVL 284

Stk1 family PASTA domain-containing Ser/Thr kinase;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720423198    1 MEFCQLGDLKRYLRAQRPpegmspeLPPRdlRTLQRMGlEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLA 79
Cdd:NF033483    86 MEYVDGRTLKDYIREHGP-------LSPE--EAVEIMI-QILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIA 154

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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd14206     76 MEFCQLGDLKRYLRAQRKADGMTPDLPTRDLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSH 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQHV 160
Cdd:cd14206    156 NNYKEDYYLTPDRLWIPLRWVAPELLDELHGNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQM 235

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 201
Cdd:cd14206    236 KLAKPRLKLPYADYWYEIMQSCWLPPSQRPSVEELHLQLSY 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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPelpprDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd05087     76 MEFCPLGDLKGYLRSCRAAESMAP-----DPLTLQRMACEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSH 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGELHGSFVLVDQSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQHV 160
Cdd:cd05087    151 CKYKEDYFVTADQLWVPLRWIAPELVDEVHGNLLVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLTYTVREQQL 230

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPRLKLPYADYWYDILQSCWRPPAQRPSASDLQLQLTY 201
Cdd:cd05087    231 KLPKPQLKLSLAERWYEVMQFCWLQPEQRPTAEEVHLLLSY 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 1720423198    1 MEFCQLGDLKRYLRAQRP--PEGMSPELPPRDLrtlQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGL 78
Cdd:cd00192     75 MEYMEGGDLLDFLRKSRPvfPSPEPSTLSLKDL---LSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGL 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   79 AHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQ 158
Cdd:cd00192    152 SRDIYDDDYYRKKTGGKLPIRWMAPESL--KDGIF-----TSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGY 224

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1720423198  159 hvKLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQLT 200
Cdd:cd00192    225 --RLPKP----ENCpDELYELMLSCWQLdPEDRPTFSELVERLE 262

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 1720423198    1 MEFCQLGDLKRYLRAQRPPegmspeLPPRDLrtLQrMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:pfam07714   80 TEYMPGGDLLDFLRKHKRK------LTLKDL--LS-MALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSR 150

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQhv 160
Cdd:pfam07714  151 DIYDDDYYRKRGGGKLPIKWMAPESL--KDGKF-----TSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGY-- 221

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPrlklPYA-DYWYDILQSCWRP-PAQRPSASDLQLQL 199
Cdd:pfam07714  222 RLPQP----ENCpDELYDLMKQCWAYdPEDRPTFSELVEDL 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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd05032     88 MELMAKGDLKSYLRSRRPEAENNPGLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMTR 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGElhGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVRQQHv 160
Cdd:cd05032    168 DIYETDYYRKGGKGLLPVRWMAPESLKD--GVF-----TTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGH- 239

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1720423198  161 klarprLKLPYA--DYWYDILQSCWR-PPAQRPSASDL 195
Cdd:cd05032    240 ------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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELpprDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTS----DLTVRIGDY 76
Cdd:cd05044     78 LELMEGGDLLSYLRAARPTAFTPPLL---TLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSkdyrERVVKIGDF 154

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   77 GLAHSNYKEDYYLTP-ERLwVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVv 155
Cdd:cd05044    155 GLARDIYKNDYYRKEgEGL-LPVRWMAPESL--VDGVF-----TTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFV- 225

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1720423198  156 rQQHVKLARPRlKLPyaDYWYDILQSCWR-PPAQRPSASDLQLQL 199
Cdd:cd05044    226 -RAGGRLDQPD-NCP--DDLYELMLRCWStDPEERPSFARILEQL 266

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198    1 MEFCQLGDLKRYLRaQRPPEGMSPEL---PPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYG 77
Cdd:cd05051     98 VEYMENGDLNQFLQ-KHEAETQGASAtnsKTLSYGTLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFG 176

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   78 LAHSNYKEDYYLTPERLWVPLRWAAPEllgelhgSFVLVDQSRESNVWSLGVTLWELFEFG-AQPYRHLSDEEVLA---- 152
Cdd:cd05051    177 MSRNLYSGDYYRIEGRAVLPIRWMAWE-------SILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTDEQVIEnage 249

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720423198  153 -FVVRQQHVKLARPRLkLPyADYwYDILQSCW-RPPAQRPSASDLQLQLT 200
Cdd:cd05051    250 fFRDDGMEVYLSRPPN-CP-KEI-YELMLECWrRDEEDRPTFREIHLFLQ 296

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 1720423198    2 EFCQLGDLKRYLRAQRP----------PEGMSPELPPRDLRTLQR--MGLEIARGLAHLHSHNYVHSDLALRNCLLTSDL 69
Cdd:cd05050     88 EYMAYGDLNEFLRHRSPraqcslshstSSARKCGLNPLPLSCTEQlcIAKQVAAGMAYLSERKFVHRDLATRNCLVGENM 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   70 TVRIGDYGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEE 149
Cdd:cd05050    168 VVKIADFGLSRNIYSADYYKASENDAIPIRWMPPESI--FYNRY-----TTESDVWAYGVVLWEIFSYGMQPYYGMAHEE 240

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1720423198  150 VLAFvVRQQHVkLARPR---LKLpyadywYDILQSCW-RPPAQRPSASDL 195
Cdd:cd05050    241 VIYY-VRDGNV-LSCPDncpLEL------YNLMRLCWsKLPSDRPSFASI 282

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 1720423198    2 EFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMG------LEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGD 75
Cdd:cd05048     88 EYMAHGDLHEFLVRHSPHSDVGVSSDDDGTASSLDQSdflhiaIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISD 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   76 YGLAHSNYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLaFVV 155
Cdd:cd05048    168 FGLSRDIYSSDYYRVQSKSLLPVRWMPPEAI--LYGKF-----TTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVI-EMI 239

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1720423198  156 RQQHVklarprlkLPYAD----YWYDILQSCWRP-PAQRPSASDLQLQL 199
Cdd:cd05048    240 RSRQL--------LPCPEdcpaRVYSLMVECWHEiPSRRPRFKEIHTRL 280

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSPELPPRDLRTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd05062     88 MELMTRGDLKSYLRSLRPEMENNPVQAPPSLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTR 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SNYKEDYYLTPERLWVPLRWAAPELLGElhGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVVrqQHV 160
Cdd:cd05062    168 DIYETDYYRKGGKGLLPVRWMSPESLKD--GVF-----TTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVM--EGG 238

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1720423198  161 KLARPRlKLPyaDYWYDILQSCWR-PPAQRPS 191
Cdd:cd05062    239 LLDKPD-NCP--DMLFELMRMCWQyNPKMRPS 267

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 1720423198    1 MEFCQLGDLKRYLRAQRPPEGMSpelpprdlrTLQRMGLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd05059     78 TEYMANGCLLNYLRERRGKFQTE---------QLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLAR 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 SnYKEDYYLTPERLWVPLRWAAPELLgeLHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVvrQQHV 160
Cdd:cd05059    149 Y-VLDDEYTSSVGTKFPVKWSPPEVF--MYSKF-----SSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHI--SQGY 218

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1720423198  161 KLARPRLKLPYAdywYDILQSCWRP-PAQRPSASDLQLQLT 200
Cdd:cd05059    219 RLYRPHLAPTEV---YTIMYSCWHEkPEERPTFKILLSQLT 256

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 1720423198    1 MEFCQLGDLKRYLRAQRppegmspELPPRDLRTLQrmgLEIARGLAHLHSHNYVHSDLALRNCLLTSDLTVRIGDYGLAH 80
Cdd:cd05060     74 MELAPLGPLLKYLKKRR-------EIPVSDLKELA---HQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSR 143

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720423198   81 S-NYKEDYY-LTPERLWvPLRWAAPELLGelHGSFvlvdqSRESNVWSLGVTLWELFEFGAQPYRHLSDEEVLAFVvrQQ 158
Cdd:cd05060    144 AlGAGSDYYrATTAGRW-PLKWYAPECIN--YGKF-----SSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAML--ES 213

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1720423198  159 HVKLARPRlKLPyaDYWYDILQSCWR-PPAQRPSASDLQLQL 199
Cdd:cd05060    214 GERLPRPE-ECP--QEIYSIMLSCWKyRPEDRPTFSELESTF 252