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 161333839 102 DNGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCA 181
Cdd:cd14143   61 DNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCC 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 182 IADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPY 261
Cdd:cd14143  141 IADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPY 220

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161333839 262 YDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQLC 329
Cdd:cd14143  221 YDLVPSDPSIEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes 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, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The TGFbR1 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 161333839 102 DNGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCA 181
Cdd:cd14143   61 DNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCC 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 182 IADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPY 261
Cdd:cd14143  141 IADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPY 220

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161333839 262 YDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQLC 329
Cdd:cd14143  221 YDLVPSDPSIEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839   109 LWLVSEYHEQGSLYDYL--NRNIVTVAGMIKLALSIASGLAHLHmeivgtqGKPAIaHRDIKSKNILVKKCETCAIADLG 186
Cdd:smart00219  76 LYIVMEYMEGGDLLSYLrkNRPKLSLSDLLSFALQIARGMEYLE-------SKNFI-HRDLAARNCLVGENLVVKISDFG 147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839   187 LAVKHDSilNTIDIPQNPKVgTKRYMAPEMLDDtmnvNIFeSFKrADIYSVGLVYWEIARRCsvggiveeyQLPYYDMvp 266
Cdd:smart00219 148 LSRDLYD--DDYYRKRGGKL-PIRWMAPESLKE----GKF-TSK-SDVWSFGVLLWEIFTLG---------EQPYPGM-- 207

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 161333839   267 sdpSIEEMRKVVcDQKFRPSIPNqwqSCEALRVmgRIMRECWYANGAARLTALRIKKTI 325
Cdd:smart00219 208 ---SNEEVLEYL-KNGYRLPQPP---NCPPELY--DLMLQCWAEDPEDRPTFSELVEIL 257

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 101 TDNGTwtqLWLVSEYHEQGSLYDYLNRN-IVTVAGMIKLALSIASGLAHLHmeivgTQGkpaIAHRDIKSKNILVKKCET 179
Cdd:COG0515   77 EEDGR---PYLVMEYVEGESLADLLRRRgPLPPAEALRILAQLAEALAAAH-----AAG---IVHRDIKPANILLTPDGR 145

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 161333839 180 CAIADLGLAVKHDSILNTidiPQNPKVGTKRYMAPEMLDDTmnvnifESFKRADIYSVGLVYWE 243
Cdd:COG0515  146 VKLIDFGIARALGGATLT---QTGTVVGTPGYMAPEQARGE------PVDPRSDVYSLGVTLYE 200

Activin types I and II receptor domain; This Pfam entry consists of both TGF-beta receptor types. This is an alignment of the hydrophilic cysteine-rich ligand-binding domains, Both receptor types, (type I and II) posses a 9 amino acid cysteine box, with the the consensus CCX{4-5}CN. The type I receptors also possess 7 extracellular residues preceding the cysteine box.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 161333839   26 LKCVC--LLC--DSSNFTCQTEGACWASVMLTNGKEQVIKSCVSLPELNAQVFCHSSNN---VTKTECCFTDFCNNI 95
Cdd:pfam01064   1 LKCYCnpLKCndDNVNFTCETDGQCFSSWELDTDGFIECVKKGCLSPEDDPFECKTSNKphsLYRIECCKTDFCNKN 77

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes 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, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The TGFbR1 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 161333839 102 DNGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCA 181
Cdd:cd14143   61 DNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVEGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCC 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 182 IADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPY 261
Cdd:cd14143  141 IADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDTINMKHFESFKRADIYALGLVFWEIARRCSIGGIHEDYQLPY 220

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 161333839 262 YDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQLC 329
Cdd:cd14143  221 YDLVPSDPSIEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLS 288

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, 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, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The BMPR1 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 161333839 103 NGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCAI 182
Cdd:cd14144   62 TGSWTQLYLITDYHENGSLYDFLRGNTLDTQSMLKLAYSAACGLAHLHTEIFGTQGKPAIAHRDIKSKNILVKKNGTCCI 141

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 183 ADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPYY 262
Cdd:cd14144  142 ADLGLAVKFISETNEVDLPPNTRVGTKRYMAPEVLDESLNRNHFDAYKMADMYSFGLVLWEIARRCISGGIVEEYQLPYY 221

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 161333839 263 DMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQL 328
Cdd:cd14144  222 DAVPSDPSYEDMRRVVCVERRRPSIPNRWSSDEVLRTMSKLMSECWAHNPAARLTALRVKKTLGKL 287

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), 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. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts 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 the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 101 TDNGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVG-TQGKPAIAHRDIKSKNILVKKCET 179
Cdd:cd13998   60 RDTALRTELWLVTAFHPNGSL*DYLSLHTIDWVSLCRLALSVARGLAHLHSEIPGcTQGKPAIAHRDLKSKNILVKNDGT 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 180 CAIADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSV-GGIVEEYQ 258
Cdd:cd13998  140 CCIADFGLAVRLSPSTGEEDNANNGQVGTKRYMAPEVLEGAINLRDFESFKRVDIYAMGLVLWEMASRCTDlFGIVEEYK 219

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 259 LPYYDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQL 328
Cdd:cd13998  220 PPFYSEVPNHPSFEDMQEVVVRDKQRPNIPNRWLSHPGLQSLAETIEECWDHDAEARLTAQCIEERLSEF 289

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, 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, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, 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. The BMPR1b 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 161333839 104 GTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCAIA 183
Cdd:cd14219   73 GSWTQLYLITDYHENGSLYDYLKSTTLDTKAMLKLAYSSVSGLCHLHTEIFSTQGKPAIAHRDLKSKNILVKKNGTCCIA 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 184 DLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPYYD 263
Cdd:cd14219  153 DLGLAVKFISDTNEVDIPPNTRVGTKRYMPPEVLDESLNRNHFQSYIMADMYSFGLILWEVARRCVSGGIVEEYQLPYHD 232

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 161333839 264 MVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQLCVKEDCK 335
Cdd:cd14219  233 LVPSDPSYEDMREIVCIKRLRPSFPNRWSSDECLRQMGKLMTECWAHNPASRLTALRVKKTLAKMSESQDIK 304

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes 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 region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 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 161333839 103 NGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGtQGKP--AIAHRDIKSKNILVKKCETC 180
Cdd:cd14055   68 VGLDRQYWLITAYHENGSLQDYLTRHILSWEDLCKMAGSLARGLAHLHSDRTP-CGRPkiPIAHRDLKSSNILVKNDGTC 146

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 181 AIADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLP 260
Cdd:cd14055  147 VLADFGLALRLDPSLSVDELANSGQVGTARYMAPEALESRVNLEDLESFKQIDVYSMALVLWEMASRCEASGEVKPYELP 226

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 161333839 261 YYDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTA 318
Cdd:cd14055  227 FGSKVRERPCVESMKDLVLRDRGRPEIPDSWLTHQGMCVLCDTITECWDHDPEARLTA 284

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a 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 161333839 107 TQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQG--KPAIAHRDIKSKNILVKKCETCAIAD 184
Cdd:cd14141   66 VDLWLITAFHEKGSLTDYLKANVVSWNELCHIAQTMARGLAYLHEDIPGLKDghKPAIAHRDIKSKNVLLKNNLTACIAD 145

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 185 LGLAVKHDSILNTIDipQNPKVGTKRYMAPEMLDDTMNVNiFESFKRADIYSVGLVYWEIARRCSVG-GIVEEYQLPYYD 263
Cdd:cd14141  146 FGLALKFEAGKSAGD--THGQVGTRRYMAPEVLEGAINFQ-RDAFLRIDMYAMGLVLWELASRCTASdGPVDEYMLPFEE 222

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 161333839 264 MVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQL 328
Cdd:cd14141  223 EVGQHPSLEDMQEVVVHKKKRPVLRECWQKHAGMAMLCETIEECWDHDAEARLSAGCVEERIIQM 287

extracellular domain (ECD) found in activin receptor-like kinase 7 (ALK-7) and similar proteins; ALK-7 (EC 2.7.11.30, also called activin receptor type-1C (ACVR1C), or activin receptor type IC (ACTR-IC)) is a serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. ALK-7 is the receptor for activin AB, activin B, and NODAL. It plays a role in cell differentiation, growth arrest and apoptosis. This model corresponds to the extracellular domain (ECD) of ALK-7, which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 161333839  24 PGLKCVCLLCDSSNFTCQTEGACWASVMLTNGKEQVIKSCVSLPELNAQVFCHSSNNVTKTECCFTDFCNNITLHL 99
Cdd:cd23540    1 TGLKCVCLLCEHTNYTCQTEGACWTSVMLTNGKEEVIKSCVSLPELNAQVFCHSSNNVTKTECCFTDFCNNITLHL 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 105 TWTQLWLVSEYHEQGSLYDYLNRN--IVTVAGMIKLALSIASGLAHLHMEivgtqgkpAIAHRDIKSKNILVKKCETCAI 182
Cdd:cd00180   62 TENFLYLVMEYCEGGSLKDLLKENkgPLSEEEALSILRQLLSALEYLHSN--------GIIHRDLKPENILLDSDGTVKL 133

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 161333839 183 ADLGLAVKHDSilNTIDIPQNPKVGTKRYMAPEMLDDTmnvnifESFKRADIYSVGLVYWEI 244
Cdd:cd00180  134 ADFGLAKDLDS--DDSLLKTTGGTTPPYYAPPELLGGR------YYGPKVDIWSLGVILYEL 187

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 161333839   109 LWLVSEYHEQGSLYDYL---NRNIVTVAGMIKLALSIASGLAHLHmeivgtqGKPAIaHRDIKSKNILVKKCETCAIADL 185
Cdd:smart00221  76 LMIVMEYMPGGDLLDYLrknRPKELSLSDLLSFALQIARGMEYLE-------SKNFI-HRDLAARNCLVGENLVVKISDF 147

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839   186 GLAVKHDSilNTIDIPQNPKVgTKRYMAPEMLDDtmnvNIFeSFKrADIYSVGLVYWEIARRCsvggiveeyQLPYYDMV 265
Cdd:smart00221 148 GLSRDLYD--DDYYKVKGGKL-PIRWMAPESLKE----GKF-TSK-SDVWSFGVLLWEIFTLG---------EEPYPGMS 209

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839   266 PsdpsiEEMRKVVcDQKFRPSIPnqwQSCEALRVmgRIMRECWYANGAARLTALRIKKTI 325
Cdd:smart00221 210 N-----AEVLEYL-KKGYRLPKP---PNCPPELY--KLMLQCWAEDPEDRPTFSELVEIL 258

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 161333839  109 LWLVSEYHEQGSLYDYL--NRNIVTVAGMIKLALSIASGLAHLH-MEIVgtqgkpaiaHRDIKSKNILVKKCETCAIADL 185
Cdd:pfam07714  76 LYIVTEYMPGGDLLDFLrkHKRKLTLKDLLSMALQIAKGMEYLEsKNFV---------HRDLAARNCLVSENLVVKISDF 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839  186 GLAVKHDSILNTIdipqnPKVGTK---RYMAPEMLDDtmnvNIFESfkRADIYSVGLVYWEIarrCSVGGIveeyqlPYY 262
Cdd:pfam07714 147 GLSRDIYDDDYYR-----KRGGGKlpiKWMAPESLKD----GKFTS--KSDVWSFGVLLWEI---FTLGEQ------PYP 206

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 161333839  263 DMVPsdpsiEEMRKVVCDqKFRPSIPNQWqsCEALRvmgRIMRECWYANGAARLTALRI 321
Cdd:pfam07714 207 GMSN-----EEVLEFLED-GYRLPQPENC--PDELY---DLMKQCWAYDPEDRPTFSEL 254

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 161333839 109 LWLVSEYHEQGSLYDYL----------NRNIVTVAGMIKLALSIASGLAHLH-MEIVgtqgkpaiaHRDIKSKNILVKKC 177
Cdd:cd00192   71 LYLVMEYMEGGDLLDFLrksrpvfpspEPSTLSLKDLLSFAIQIAKGMEYLAsKKFV---------HRDLAARNCLVGED 141

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 178 ETCAIADLGLAVKHDSILNTIDipqnpKVGTK---RYMAPEMLDDtmnvNIFeSFKrADIYSVGLVYWEIarrCSVGGIv 254
Cdd:cd00192  142 LVVKISDFGLSRDIYDDDYYRK-----KTGGKlpiRWMAPESLKD----GIF-TSK-SDVWSFGVLLWEI---FTLGAT- 206

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 161333839 255 eeyqlPYYDMVPsdpsiEEMRKVVCDQkFRPSIPnqwQSC-EALRvmgRIMRECW 308
Cdd:cd00192  207 -----PYPGLSN-----EEVLEYLRKG-YRLPKP---ENCpDELY---ELMLSCW 244

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 161333839 114 EYHEQGSLYDYLNR--NIVTVAGMIKLALSIASGLAHLHmeivgTQGkpaIAHRDIKSKNILVKKCETCAIADLGLAVKH 191
Cdd:cd13979   82 EYCGNGTLQQLIYEgsEPLPLAHRILISLDIARALRFCH-----SHG---IVHLDVKPANILISEQGVCKLCDFGCSVKL 153

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 192 DSiLNTIDIPQNPKVGTKRYMAPEML---DDTmnvnifesfKRADIYSVGLVYWEIARRcsvggiveeyQLPYydmvpsd 268
Cdd:cd13979  154 GE-GNEVGTPRSHIGGTYTYRAPELLkgeRVT---------PKADIYSFGITLWQMLTR----------ELPY------- 206

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 161333839 269 psiEEMRKV----VCDQKFRPSIPNQWQSCEALRvMGRIMRECWYANGAARLTA 318
Cdd:cd13979  207 ---AGLRQHvlyaVVAKDLRPDLSGLEDSEFGQR-LRSLISRCWSAQPAERPNA 256

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 114 EYHEQGSLYDYLNR----NIVTVagmIKLALSIASGLAHLHmeivgTQGkpaIAHRDIKSKNILVKKCETCAIADLGLAV 189
Cdd:cd06606   79 EYVPGGSLASLLKKfgklPEPVV---RKYTRQILEGLEYLH-----SNG---IVHRDIKGANILVDSDGVVKLADFGCAK 147

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 161333839 190 KHDSILNTidIPQNPKVGTKRYMAPEMLDDTmnvnifESFKRADIYSVGLVYWEIA 245
Cdd:cd06606  148 RLAEIATG--EGTKSLRGTPYWMAPEVIRGE------GYGRAADIWSLGCTVIEMA 195

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK 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 161333839 111 LVSEYHEQGSLYDYLNRNIVTVAGMIKL---ALSIASGLAHLHMEivgtqGKPAIAHRDIKSKNILVKKCETCAIADLGL 187
Cdd:cd14060   59 IVTEYASYGSLFDYLNSNESEEMDMDQImtwATDIAKGMHYLHME-----APVKVIHRDLKSRNVVIAADGVLKICDFGA 133

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161333839 188 AVKH-DSILNTIdipqnpkVGTKRYMAPEMLDDtmnvniFESFKRADIYSVGLVYWE-IARRCSVGGIvEEYQLPYydmv 265
Cdd:cd14060  134 SRFHsHTTHMSL-------VGTFPWMAPEVIQS------LPVSETCDTYSYGVVLWEmLTREVPFKGL-EGLQVAW---- 195

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 161333839 266 psdpsieemrkVVCDQKFRPSIPnqwQSCEalRVMGRIMRECWYANGAAR 315
Cdd:cd14060  196 -----------LVVEKNERPTIP---SSCP--RSFAELMRRCWEADVKER 229