3H9R,3MY0


Conserved Protein Domain Family
STKc_ACVR1_ALK1

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cd14142: STKc_ACVR1_ALK1 
Click on image for an interactive view with Cn3D
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1
STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, 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 ACVR1 and ALK1, 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 ACVR1 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.
Statistics
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PSSM-Id: 271044
Aligned: 12 rows
Threshold Bit Score: 602.507
Created: 6-Apr-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 26 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:includes ATP binding and substrate binding sites
  • Structure:3H9R: Human ACVR1 kinase domain binds dorsomorphin and sulfate ions in the active site; contacts at 4A.
  • Comment:also based on similarity to other members of the superfamily

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    #####   #          # #                           #                  
3H9R_A        33 RTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSRDEKSWFRETELYNTVMlRHENILGFIASDMTSrhsSTQLWL 112 human
3MY0_A         4 RTVARQVALVECVGKGRYGEVWRGLWHGESVAVKIFSSRDEQSWFRETEIYNTVLlRHDNILGFIASDMTSrnsSTQLWL 83  human
BAE06725     230 RTMARQIQLVNCIGKGRYGAVWKGMWQDEPVAVKVFASRDEQSWARETEIYNTVLlRHSNILGYIASDMISrnsDTELWL 309 Ciona intestinalis
NP_989891    197 RTVARQITLVECVGKGRYGEVWRGQWQGENVAVKIFSSRDEKSWFRETELYNTVLlRHENILGFIASDMTSrnsSTQLWL 276 chicken
NP_001083727 200 RTVARQITLAECVGKGRYGEVWRGLWQGESVAVKIFSSRDEKSWFRETELYNTVLlRHENILGFIASDMTSrnsSTQLWL 279 African clawed ...
XP_002598018 143 RTVARQITLVEQIGKGRYGEVWRGQWQGENVAVKIFNSRDEKSWFRETEIYNTVLlRHENILGFIASDMTSrnsCTQLWL 222 Florida lancelet
NP_571420    199 RTVARQISLVECVGKGRYGEVWRGQWQGENVAVKIFSSRDEKSWFRETEIYNTVLlRHENILGFMASDMTSrnsSTQLWL 278 zebrafish
CAC85263     223 ATVARSISLIECIGKGRYGSVWRGRYHDENLAVKIFSSRDEASWLRETEIYNTCLlRHEGILGYYASDMTSrnsCTQLWL 302 Pacific oyster
ACX32975     262 RTLAKQVTLIECIGRGKYGEVWRGHWHGESIAVKIFFSRDEESWKRETEIYSTILlRHENILGFIGSDMTSrnsCTQLWL 341 fruit fly
XP_794984    198 RTVARQINLLQQVGKGRYGEVWMGTWQGDTVAVKIFSSIDEKSWFRETEIYNTVMlRHENILAFFASDMTSrqsCTQLWL 277 purple urchin
XP_002412384   1 MALAEHLNQTKERGKGRYGEVWCGVWFGESVAVKIFSSRDEASWSRETEIYSTVLmRHENILGYLGSDVTShnsCTQLWL 80  black-legged tick
XP_002169299 270 RTVARQIILVDLIGKGRYGEVWRGDWHGESVAVKIFNSRDEDSWKRETQIYNTVMlRHDNILGYIASDIAVkkdETCMWL 349 green hydra
Feature 1         ####   # #                                           # # ## #          #  #    
3H9R_A       113 ITHYHEmGSLYDYLQLttlDTVSCLRIVLSIASGLAHLHIEIfgtqGKPAIAHRDLKSKNILVKknGQCCIADLGLAVMH 192 human
3MY0_A        84 ITHYHEhGSLYDFLQRqtlEPHLALRLAVSAACGLAHLHVEIfgtqGKPAIAHRDFKSRNVLVKsnLQCCIADLGLAVMH 163 human
BAE06725     310 VCYYHPnGSLYEYLQHnelDHQLMLQLCLSAANGLTHLHTDIlgvcGKAAIAHRDVKSKNILVKsdLTCCIADLGLAVTH 389 Ciona intestinalis
NP_989891    277 ITHYHEmGSLYDYLQLttlDTVSCLRIVLSIASGLAHLHIEIfgtqGKPAISHRDLKSKNILVKknGQCCIADLGLAVMH 356 chicken
NP_001083727 280 ITHYHElGSLYDYLQVttlDSVTCLRIVLSIASGLAHLHVEIfgtqGKPAISHRDLKSKNILVRknGQCCIADLGLAVMH 359 African clawed ...
XP_002598018 223 ITHYHEyGSLYDFLQRttlDAHRMMKLACSIAGGLVHLHVEIfgtqGKPAIAHRDLKSKNILVKsnGQCCIADLGLAVMH 302 Florida lancelet
NP_571420    279 ITHYHEnGSLYDYLQRvavEMADGLHMAASIASGLVHLHTEIfgteGKPAIAHRDLKSKNILVKkdLQCCIADLGLAVTH 358 zebrafish
CAC85263     303 IMHYHEnGSLYDYLQSttlDHEEMLRLCHSAAAGIVHLHTEIvgnhGKPAIAHRDIKSKNILVKgnGTCCIGDLGLAVTH 382 Pacific oyster
ACX32975     342 MTHYYPlGSLFDHLNRnalSHNDMVWICLSIANGLVHLHTEIfgkqGKPAMAHRDLKSKNILVTsnGSCVIADFGLAVTH 421 fruit fly
XP_794984    278 IMEYHErGSLYDYLNRhvlDARQMCRLALTACSGLVHLHTEItcnnSKPAIAHRDIKTKNILVKrnLTCCIADLGLAVLH 357 purple urchin
XP_002412384  81 VTPYLQaGSLYDWLSTaplSSQQMMAVALSTVSGIVHLHTEIygtqGKPAIAHRDIKTKNILVKanGTCVIADFGLAVTH 160 black-legged tick
XP_002169299 350 IAHYHEhGSLYDYLNThslSVYEMALISHSAVCGLVHLHTEIngmqGKPAIAHRDIKTKNILVKsnGQCCISDLGLAVLH 429 green hydra
Feature 1                        ####                                                            
3H9R_A       193 SQST-NQLDVGNNPRVGTKRYMAPEVLDETIQVDcfDSYKRVDIWAFGLVLWEVARRMVSngIVEDYKPPFYDVVPNdpS 271 human
3MY0_A       164 SQGS-DYLDIGNNPRVGTKRYMAPEVLDEQIRTDcfESYKWTDIWAFGLVLWEIARRTIVngIVEDYRPPFYDVVPNdpS 242 human
BAE06725     390 NPEEgKIVIPKNNHRVGTKRYMSPEVLDESLNTSsfECFKQADVYSFGLVLWEVARRCVSggIVETYQPPFYDVVGYdpS 469 Ciona intestinalis
NP_989891    357 SQST-NQLDVGNNPRVGTKRYMAPEVLDETIQADcfDSYKRVDIWAFGLVLWEVARRMVSngIVEDYKPPFYDLVPNdpS 435 chicken
NP_001083727 360 SQTT-NQLDVGNNPRVGTKRYMAPEVLDETIQVDcfDSYKRVDIYAFGLVLWEVARRMVSngIVEEYKPPFYDVVPNdpS 438 African clawed ...
XP_002598018 303 SQAT-DTLDLGSNPRVGTKRYMAPELLEEIMNYEcfDSYKRVDVYALGLVLWEVARRCTSggIAEEYKPPYYDVVPSdpS 381 Florida lancelet
NP_571420    359 TQSD-NQLDVGNNPKVGTKRYMAPEVLDETIQTDcfDAYKRVDIWAFGLVLWEIARRTISngIVEEYKPPFYDLVPNdpS 437 zebrafish
CAC85263     383 TQEN-NKIDLGRNNKVGTKRYMAPELLDETLNPEyfEAFKQVDVYAFGLVMWEIARRCVAegMVDDYKPPFWDVVPSdpS 461 Pacific oyster
ACX32975     422 SHVT-GQLDLGNNPKVGTKRYMAPEVLDESIDLEcfEAVRRTDIYAFGLVLWEVCRRTIScgIAEEYKVPFYDVVPMdpS 500 fruit fly
XP_794984    358 TQRE-DNIDMGTNTRVGTKRYMAPELLEETMDVRcfESFKRVDVYAFGLVMWEIARRCEVggMVADYKPPFFEYVPSdpS 436 purple urchin
XP_002412384 161 RQAT-GQLNIAHNHRVGTKRYMAPELLDETLNTSafESYRRVDIYALGLVLWEVCRRCLSggIAEEYMPPFYDMVPSdpS 239 black-legged tick
XP_002169299 430 SKES-NCLDVSCNRRVGTKRYMAPELLTETMCMTsfDAYKHADMYAFGLVLWEIARRTEFqgIVEEYQPPYYDYLPQdpS 508 green hydra
Feature 1                                                                   
3H9R_A       272 FEDMRKVVCVdQQRPNIPNRWfsdptLTSLAKLMKECWYQnPSARLTaLRIKKTLTKID 330 human
3MY0_A       243 FEDMKKVVCVdQQTPTIPNRLaadpvLSGLAQMMRECWYPnPSARLTaLRIKKTLQKIS 301 human
BAE06725     470 FDEMRKVVCVdGYRPVVPNRWtsddtLSIISKILRETWCKtPSNRLTiHRVKKSLLKAT 528 Ciona intestinalis
NP_989891    436 FEDMRKVVCVdQQRPNIPNRWfsdptLTSLAKLMKECWYQnPSARLTaLRIKKTLTKID 494 chicken
NP_001083727 439 FEDMKKVVCVdQQRPNIPNRWfsdptLTALAKLMKECWYHnPSARLTaLRIKKTLTKID 497 African clawed frog
XP_002598018 382 YEDMRKVVVEgQQRPSIPNRWssdqtLTAMAKLMRECWYHnPAARLTaLRVKKTLNKLQ 440 Florida lancelet
NP_571420    438 FDDMRKVVCVeQQRPFIPNRWfsdptLSALVKLMKECWYQnPSARLTaLRIKKTLDKIH 496 zebrafish
CAC85263     462 FDDMKKVVVIdQQRPAIPNRWsadpiLLLMSKVIQECWTCnPKARLTiLRIKKTLNQLL 520 Pacific oyster
ACX32975     501 FEDMRKVVCIdNYRPSIPNRWssdslMTGMSKLMKECWHQnPDVRLPaLRIKKTIHKLA 559 fruit fly
XP_794984    437 FDDMRKVACIeKLRPNIPNRWtnntvLTSMAKLMKECWCPtASARHTsLRVKKTLMKIS 495 purple urchin
XP_002412384 240 FEDMRKVVVVdQQRPVIPNRWssdptLVATAKLMKECWHHnPSARLTaLRMKKSLLKIA 298 black-legged tick
XP_002169299 509 FEEVKKVVVDdHYRPDIPKHWlndenALKFSKVMRECWREePTARLSaLRVKKSLSKLL 567 green hydra

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