1VJY,2WOT,1B6C,1PY5


Conserved Protein Domain Family
STKc_TGFbR1_ACVR1b_ACVR1c

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cd14143: STKc_TGFbR1_ACVR1b_ACVR1c 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 271045
Aligned: 19 rows
Threshold Bit Score: 548.582
Created: 11-May-2010
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Comment:also based on the binding of MgADP or inhibitor to other members of the TGFbeta Receptor subfamily
  • Structure:1VJY_A; Human TGFbR1 binds naphthyridine inhibitor; contacts at 4A.
  • Structure:2WOT_A; Human TGFbR1 binds inhibitor; contacts at 4A.
  • Structure:1PY5: Human TGFbR1 binds pyrazole inhibitor; contacts at 4A.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1          ####### #          # #                                               ## #   # 
1VJY_A         9 ESIGKGRFGEVWRGKWRGEEVAVKIFSSreERSWFREAEIYQTVMlRHENILGFIAADNKDNGTWTQLWLVSDYHehGSL 88  human
AAQ22445     301 HVIGKGRFGEVWRGRWRGENVAVKIFSSreECSWFREAEIYQTVMlRHENILGFIAADNKDNGTWTQLWLVTDYHenGSL 380 fruit fly
BAE06727     208 EVIGKGRYGEVFRGKWRGEDVAVKKFVTrdERSWAREAEIYQTIMlRHENILGFIAADNKDVGTWTELWLISEYHenGSL 287 Ciona intestinalis
CAD66433     216 EIIGKGRYGEVWSGRWRAENVAVKIFSSreERSWIREAEIYQTVMlRHENILGFIAADNKDNGTWTQLWLITDYHanGSL 295 Pacific oyster
XP_002412676 211 EIIGKGRYGEVWRGRWRGESVAVKIFSSrdERSWFREVEIYQTVMlRHDNILGFIAADNKDNGTWTQLWLITDYHenGSL 290 black-legged tick
XP_001622534 186 ELIGSGRYGDVYRGQWRGEDVAVKIFSSreECSWFREAQIYQTVMlRHENILGFIAADNKDNGAWTQLWLITDYHanGSL 265 starlet sea ane...
Q8NER5       199 EIVGKGRFGEVWHGRWCGEDVAVKIFSSrdERSWFREAEIYQTVMlRHENILGFIAADNKDNGTWTQLWLVSEYHeqGSL 278 human
CAG09326     177 ESIGKGRFGEVWRGKWRGEDVAVKIFSSrdERSWFREAEIYQTIMlRHENILGFIAADNKDSGSWTQLWLVSEYHehGSL 256 spotted green p...
NP_571065    211 EIIGKGRFGEVWRGRWRGGDVAVKIFSSreERSWFREAEIYQTIMlRHENILGFIAADNKDNGTWTQLWLVSDYHehGSL 290 zebrafish
NP_001084349 204 EIIGKGRFGEVWRGKWRGGDVAVKIFSSreERSWFREAEIYQTVIwRHENILGFIAADNKDNGTWTQLWLVSDYHehGSL 283 African clawed ...
Feature 1                                                           ## #           #             
1VJY_A        89 FDYLNRYtvTVEGMIKLALSTASGLAHLHMEIVgt---qGKPAIAHRDLKSKNILVKKN-GTCCIADLGLAVRHDSATDT 164 human
AAQ22445     381 FDYLTTHpvDTNTMLNMSLSIATGLAHLHMDIVgt---rGKPAIAHRDLKSKNILVKSN-LSCAIGDLGLAVRHVEKNDS 456 fruit fly
BAE06727     288 FDYLGETrvDVGAMLKLCSSIASGLAHLHNEIVgt---lGKPPIAHCDLKSKNILVKKN-GECAIADLGLAVRHDSSTDT 363 Ciona intestinalis
CAD66433     296 FDYLNRTvlSTTQMIRLAMSAACGLAHLHMDIVgteihaGKPAIAHRDLKSKNILVRNDgVSCCIADLGLAVRHDPVTDA 375 Pacific oyster
XP_002412676 291 FDYLTRIpvDTSTMCKMAYSIANGLAHLHMEILgt---qGKPAIAHRDMKSKNILVKCN-GTCAIADLGLAVRYDSASNT 366 black-legged tick
XP_001622534 266 YDYLQRVtlDMKSMLKLTISIASGLAHLHMEIIgt---qGKPAIAHRDLKSRNILVKDN-GTCCIADLGLAVCHNSEQDT 341 starlet sea ane...
Q8NER5       279 YDYLNRNivTVAGMIKLALSIASGLAHLHMEIVgt---qGKPAIAHRDIKSKNILVKKC-ETCAIADLGLAVKHDSILNT 354 human
CAG09326     257 YDYLNRYtlPVEAMAVLALSVASGLAHLHMEIIgt---qGKPAIAHRDLKSKNILVKKN-GTAAIADLGLAVKHDSTTNT 332 spotted green p...
NP_571065    291 FDYLNHYsvTIEGMIKLSLSAASGLAHLHMEILgt---qGKPGIAHRDLKSKNILVKKN-GIFAIADLGLAVRHESITDT 366 zebrafish
NP_001084349 284 FDYLNRYtvTIEGMIKLALSAASGLAHLHMEIVgt---qGKPGIAHRDLKSKNILVKKN-GMCAIADLGLAVRHDSATDT 359 African clawed ...
Feature 1                                                                                        
1VJY_A       165 IDIAPNHRVGTKRYMAPEVLDDSINMKhFESFKRADIYAMGLVFWEIARRCSIGgIHEDYQLPYYDLVPSDPSVEEMRKV 244 human
AAQ22445     457 VDIPSTHRVGTKRYMAPEVLDESMNDQhFDSYKRADVYAFGLILWEIARRCNMGmIYDEYQLPYYDVVQPDPSIEEMKKV 536 fruit fly
BAE06727     364 IDIPPNNRVGTKRYMAPEILDDTLNMLhFDSFKRADIYSLGLVLWEIGRRCSIGgQNLDYQLPYYNMVPDDPTIEQMRVV 443 Ciona intestinalis
CAD66433     376 VDIAPNNRVGTKRYMAPEVLSDTISMNqFDSFKRADVYSFGLVLWEITRRCSVGgIVEDYQLPFYDIVPSDPSLEDMKKV 455 Pacific oyster
XP_002412676 367 VDIPPNPRVGTKRYLAPEVLDETINMNhFDSFKRADIYAFGLVLWELARRCSIGgIYEDYQLPYYDLVPSDPTIEEMRKV 446 black-legged tick
XP_001622534 342 LDIPYGNRVGTRRYMAPEFLEDSNQVRnFCAYKHGDIYAFGLVLWEITRRCICSdKCEDYQLPYFDKICVDPSIEEVWKV 421 starlet sea ane...
Q8NER5       355 IDIPQNPKVGTKRYMAPEMLDDTMNVNiFESFKRADIYSVGLVYWEIARRCSVGgIVEEYQLPYYDMVPSDPSIEEMRKV 434 human
CAG09326     333 VDIPSNHRVGTKRYMAPEILDETINTQsFESFKRADIYSLGLVFWELARRCSVRgLHEDFQLPYYDLVPSDPTIEDMRKV 412 spotted green p...
NP_571065    367 IDIAPNQRVGTKRYMAPEVLDETINMKhFDSFKCADIYALGLVYWEIARRCNAGgIHEDYKLPYYDLVPSDPSIEEMRKV 446 zebrafish
NP_001084349 360 IDIAPNQRVGTKRYMAPEVLDETINMKhFDSFKCADIYALGLVYWEIARRCSTGgFHEEYQLPFYDLVPSDPSIEEMRKV 439 African clawed ...
Feature 1                                                            
1VJY_A       245 VCEQKLRPNIPNRWqsceALRVMAKIMRECWYAnGAARLTaLRIKKTLSQLS 296 human
AAQ22445     537 VCIEKCRPNIPNRWhasdVLHNMAKVMKECWYPnPVARLTaLRIKKTLASIS 588 fruit fly
BAE06727     444 VCEKMFRPQKEATWhkydTMERMWKLMNECWYEsGCARLTaLRVKKTIAKIE 495 Ciona intestinalis
CAD66433     456 VCDDRQRPGIPNRWqtieSLKVMSRLMRECWYHnPAARLTtLRIKKSLDNLA 507 Pacific oyster
XP_002412676 447 ACTDRQRPALPNRWqsceALRVMSKIMKECWYHnSAARLTaLRIKKTIANLG 498 black-legged tick
XP_001622534 422 VCLEKYRPSHPNYWlqdqVMMRVAKLMQECWHHsPEARLPaLRIKKTLQSLY 473 starlet sea anemone
Q8NER5       435 VCDQKFRPSIPNQWqsceALRVMGRIMRECWYAnGAARLTaLRIKKTISQLC 486 human
CAG09326     413 VCEQKLRPSVPNQWqsceALRVMGRLMRECWYAnPSARLTaLRVKKTVSQLS 464 spotted green pufferfish
NP_571065    447 VCDQRLRPKWPNWWqsyeALRVMGKIMRECWYAnGAARLTaLRIKKTLSQLS 498 zebrafish
NP_001084349 440 VCDQKLRPNIPNWWqsyeALRVMGKMMRECWYAnGAARLTaLRIKKTLSQLS 491 African clawed frog

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