1MQB,2GSF,2HEN


Conserved Protein Domain Family
PTKc_EphR

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cd05033: PTKc_EphR (this model, PSSM-Id:133165 is obsolete and has been replaced by 270629)
Click on image for an interactive view with Cn3D
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases
Protein Tyrosine Kinase (PTK) family; Ephrin Receptor (EphR) subfamily; catalytic (c) domain. The PTKc family 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). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EhpB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.
Statistics
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PSSM-Id: 133165
Aligned: 12 rows
Threshold Bit Score: 496.861
Threshold Setting Gi: 33112463
Created: 17-Jul-2006
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs as well as, the structures of human EphA2 receptor bound with an ATP analog and mouse EphB2 receptor tyr kinase bound with ADP, (1MQB_B, 2HEN_A respectively).
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    # ###   #                                       # #                  
1MQB_B         41 IHPSCVTRqKVIGAGEFGEVYKGMLKtss-----------------------gkKEVPVAIKTLKAGYTEkQRVDFLGEA 97   human
2GSF_A         42 LDATNISIdKVVGAGEFGEVCSGRLKlp------------------------skKEISVAIKTLKVGYTEkQRRDFLGEA 97   human
2HEN_A          4 IDISCVKIeQVIGAGEFGEVCSGHLKlp------------------------gkREIFVAIKTLKSGYTEkQRRDFLSEA 59   house mouse
O61460        687 ISPNDVFItQVIGGGEFGDVCLGGLSknspaaakwsvsnttmgrggggggyesePYETVAIKTLKSGSSAkAKAEFLTEA 766  nematode
P21709        619 LDPAWLMVdTVIGEGEFGEVYRGTLRlp------------------------sqDCKTVAIKTLKDTSPGgQWWNFLREA 674  human
Q5JZY3        640 LDAKSVTLeRSLGGGRFGELCCGCLQlp------------------------grQELLVAVHMLRDSASDsQRLGFLAEA 695  human
BAE06403      638 IDASYIGIeEVIGGGEFGEVCLGRMRlpn-----------------------skKEHDVAIKTLKAGYSTqQKLDFLGEA 694  Ciona intesti...
NP_524625     736 IDANYITIeAIIGGGEFGDVCRGRLKipp----------------------nfvQDIDVAIKTLKPGSSEkARCDFLTEA 793  fruit fly
BAA81719      530 IPPKYIKLvEEIGGGEFGTVYKGMWNer-------------------------kPPVPIAVKTLKPGSSDkMRDDFLTEA 584  Ephydatia flu...
BAE06404      711 TDPDLVSInKVIGCGEFGEVYQGSLTltdt--------------------ggkrKVIDVAIKQLHAQCQPnEQIDFLHEA 770  Ciona intesti...
XP_001196893  383 IDATQIRIlEVIGGGEFGDVCSGLMLmp------------------------dkTTIKVAVKTLKTGATDkDRSDFLSEA 438  purple urchin
NP_989691     611 LDVSCVTMeNVIGEGEFGEVYRGSLRlp------------------------gkERIVVAIKTLKSTYSDsQWWNFLREA 666  chicken
2GSF_A         42 LDATNISIdKVVGAGEFGEVCSGRLKlp------------------------skKEISVAIKTLKVGYTEkQRRDFLGEA 97   human
2HEN_A          4 IDISCVKIeQVIGAGEFGEVCSGHLKlp------------------------gkREIFVAIKTLKSGYTEkQRRDFLSEA 59   house mouse
O61460        687 ISPNDVFItQVIGGGEFGDVCLGGLSknspaaakwsvsnttmgrggggggyesePYETVAIKTLKSGSSAkAKAEFLTEA 766  nematode
P21709        619 LDPAWLMVdTVIGEGEFGEVYRGTLRlp------------------------sqDCKTVAIKTLKDTSPGgQWWNFLREA 674  human
Q5JZY3        640 LDAKSVTLeRSLGGGRFGELCCGCLQlp------------------------grQELLVAVHMLRDSASDsQRLGFLAEA 695  human
BAE06403      638 IDASYIGIeEVIGGGEFGEVCLGRMRlpn-----------------------skKEHDVAIKTLKAGYSTqQKLDFLGEA 694  Ciona intesti...
NP_524625     736 IDANYITIeAIIGGGEFGDVCRGRLKipp----------------------nfvQDIDVAIKTLKPGSSEkARCDFLTEA 793  fruit fly
BAA81719      530 IPPKYIKLvEEIGGGEFGTVYKGMWNer-------------------------kPPVPIAVKTLKPGSSDkMRDDFLTEA 584  Ephydatia flu...
BAE06404      711 TDPDLVSInKVIGCGEFGEVYQGSLTltdt--------------------ggkrKVIDVAIKQLHAQCQPnEQIDFLHEA 770  Ciona intesti...
XP_001196893  383 IDATQIRIlEVIGGGEFGDVCSGLMLmp------------------------dkTTIKVAVKTLKTGATDkDRSDFLSEA 438  purple urchin
NP_989691     611 LDVSCVTMeNVIGEGEFGEVYRGSLRlp------------------------gkERIVVAIKTLKSTYSDsQWWNFLREA 666  chicken
Feature 1                                    ## #                                                 
1MQB_B         98 GIMGQFSHHNIIRLEGVISkykPMMIITEYMENGALDKFLREKdg---eFSVLQLVGMLRGIAAGMKYLAN-----MNYV 169  human
2GSF_A         98 SIMGQFDHPNIIRLEGVVTkskPVMIVTEYMENGSLDSFLRKHda---qFTVIQLVGMLRGIASGMKYLSD-----MGYV 169  human
2HEN_A         60 SIMGQFDHPNVIHLEGVVTkstPVMIITEFMENGSLDSFLRQNdg---qFTVIQLVGMLRGIAAGMKYLAD-----MNYV 131  house mouse
O61460        767 TIMGQFSHPNVIRLIGVVTsaePVMIVAEYMANGSLDQFLRNTdqrgekVHWEKITEMLYGIASGMKYLTDmgyvhRVSF 846  nematode
P21709        675 TIMGQFSHPHILHLEGVVTkrkPIMIITEFMENGALDAFLRERed---qLVPGQLVAMLQGIASGMNYLSN-----HNYV 746  human
Q5JZY3        696 LTLGQFDHSHIVRLEGVVTrgsTLMIVTEYMSHGALDGFLRRHeg---qLVAGQLMGLLPGLASAMKYLSE-----MGYV 767  human
BAE06403      695 SIMGQFDHPNVIRLEGVVTksqPHMIITEYMENGSLDTFLRKHdg---eFTVIQLVGILRNIAAGMKYLSD-----MGYV 766  Ciona intesti...
NP_524625     794 SIMGQFDHPNVIYLQGVVTrsnPVMIITEYMENGSLDTFLRVNdg---kFQTLQLIVMLRGIASGMSYLSD-----MNYV 865  fruit fly
BAA81719      585 SIMGQFHHPNVIKLYGVITkvePAMIIMEFMDNGSLYYYLRHNde---kLSLQQLLKMACGVAAGMQYLSE-----VGYV 656  Ephydatia flu...
BAE06404      771 KALERFQHPNIVKLEAVVMasrPFMIVTELMVNGCLGKFLRHHrgakryFKPTVLVRMLHGVAKGMAYLSK-----MCYV 845  Ciona intesti...
XP_001196893  439 SIMGQFDHPNVIKLLGVVTktrPAMIVTEFMENGSLDKYLRENdg---rFTVTQLLGMMRGVGFGMRFLSE-----MNFV 510  purple urchin
NP_989691     667 TIMGQFNHPNIVHLEGVVTkrrPMMIITEYMENGALDTFLRENee---kFSPVQLVNMLQGIASGMTYLSE-----HNYV 738  chicken
2GSF_A         98 SIMGQFDHPNIIRLEGVVTkskPVMIVTEYMENGSLDSFLRKHda---qFTVIQLVGMLRGIASGMKYLSD-----MGYV 169  human
2HEN_A         60 SIMGQFDHPNVIHLEGVVTkstPVMIITEFMENGSLDSFLRQNdg---qFTVIQLVGMLRGIAAGMKYLAD-----MNYV 131  house mouse
O61460        767 TIMGQFSHPNVIRLIGVVTsaePVMIVAEYMANGSLDQFLRNTdqrgekVHWEKITEMLYGIASGMKYLTDmgyvhRVSF 846  nematode
P21709        675 TIMGQFSHPHILHLEGVVTkrkPIMIITEFMENGALDAFLRERed---qLVPGQLVAMLQGIASGMNYLSN-----HNYV 746  human
Q5JZY3        696 LTLGQFDHSHIVRLEGVVTrgsTLMIVTEYMSHGALDGFLRRHeg---qLVAGQLMGLLPGLASAMKYLSE-----MGYV 767  human
BAE06403      695 SIMGQFDHPNVIRLEGVVTksqPHMIITEYMENGSLDTFLRKHdg---eFTVIQLVGILRNIAAGMKYLSD-----MGYV 766  Ciona intesti...
NP_524625     794 SIMGQFDHPNVIYLQGVVTrsnPVMIITEYMENGSLDTFLRVNdg---kFQTLQLIVMLRGIASGMSYLSD-----MNYV 865  fruit fly
BAA81719      585 SIMGQFHHPNVIKLYGVITkvePAMIIMEFMDNGSLYYYLRHNde---kLSLQQLLKMACGVAAGMQYLSE-----VGYV 656  Ephydatia flu...
BAE06404      771 KALERFQHPNIVKLEAVVMasrPFMIVTELMVNGCLGKFLRHHrgakryFKPTVLVRMLHGVAKGMAYLSK-----MCYV 845  Ciona intesti...
XP_001196893  439 SIMGQFDHPNVIKLLGVVTktrPAMIVTEFMENGSLDKYLRENdg---rFTVTQLLGMMRGVGFGMRFLSE-----MNFV 510  purple urchin
NP_989691     667 TIMGQFNHPNIVHLEGVVTkrrPMMIITEYMENGALDTFLRENee---kFSPVQLVNMLQGIASGMTYLSE-----HNYV 738  chicken
Feature 1           #   ## #          #                      #####        #                       
1MQB_B        170 HRDLAARNILVNSnLVCKVSDFGLSRVLed---dPEATYTTS-GGKIPIRWTAPEAISYrKFTSASDVWSFGIVMWEVMT 245  human
2GSF_A        170 HRDLAARNILINSnLVCKVSDFGLSRVLed---dPEAAYTTR-GGKIPIRWTSPEAIAYrKFTSASDVWSYGIVLWEVMS 245  human
2HEN_A        132 HRALAARNILVNSnLVCKVSDFGLSRFLed--dtSDPTYTSAlGGKIPIRWTAPEAIQYrKFTSASDVWSYGIVMWEVMS 209  house mouse
O61460        847 LRDLAARNVLLDMeLRCKIADFGLSRGVrsegssVEPEYTTN-GGKIPVRWTAPEAITHrKFTPSSDVWSFGVVIWEVCS 925  nematode
P21709        747 HRDLAARNILVNQnLCCKVSDFGLTRLLd----dFDGTYETQ-GGKIPIRWTAPEAIAHrIFTTASDVWSFGIVMWEVLS 821  human
Q5JZY3        768 HRGLAARHVLVSSdLVCKISGFGRGPRDr-----SEAVYTTM-SGRSPALWAAPETLQFgHFSSASDVWSFGIIMWEVMA 841  human
BAE06403      767 HRDLAARNILVNAqLICKVSDFGLSRVLee---sSDSTYTTR-GGKIPIRWTAPEAINYrKFTSASDVWSYGIVMWEVMS 842  Ciona intesti...
NP_524625     866 HRDLAARNVLVNAqLICKIADFGLSREIe----nASDAYTTR-GGKIPVRWTAPEAIAFrKFTSASDVWSYGVVLWEVMS 940  fruit fly
BAA81719      657 HRDLAARNILVSKdEVCKVADFGLSRET------TNDEYDVKkGGKIPVRWTAPEAISYrKFTTASDVWSYGVLLWEVMS 730  Ephydatia flu...
BAE06404      846 HRDLAARNVLINNeLVCKVADFGLIRHIg----eKKSTVNTK-GGKISLRWTAPEAVAYqAYSQASDVWSFGVFAWEVIT 920  Ciona intesti...
XP_001196893  511 HRDLAARNILVNEhLVCKVADFGLSRRKe-----LDGAYETR-GGKIPIRWTAPEAIGYkKFTSASDVWSLGVVMWEIMS 584  purple urchin
NP_989691     739 HRDLAARNILVTRsLQCKVSDFGLSRILen---dAEGTYETK-GGKIPIRWTAPEAIAHrIFTSASDVWSFGIVMWEVLS 814  chicken
2GSF_A        170 HRDLAARNILINSnLVCKVSDFGLSRVLed---dPEAAYTTR-GGKIPIRWTSPEAIAYrKFTSASDVWSYGIVLWEVMS 245  human
2HEN_A        132 HRALAARNILVNSnLVCKVSDFGLSRFLed--dtSDPTYTSAlGGKIPIRWTAPEAIQYrKFTSASDVWSYGIVMWEVMS 209  house mouse
O61460        847 LRDLAARNVLLDMeLRCKIADFGLSRGVrsegssVEPEYTTN-GGKIPVRWTAPEAITHrKFTPSSDVWSFGVVIWEVCS 925  nematode
P21709        747 HRDLAARNILVNQnLCCKVSDFGLTRLLd----dFDGTYETQ-GGKIPIRWTAPEAIAHrIFTTASDVWSFGIVMWEVLS 821  human
Q5JZY3        768 HRGLAARHVLVSSdLVCKISGFGRGPRDr-----SEAVYTTM-SGRSPALWAAPETLQFgHFSSASDVWSFGIIMWEVMA 841  human
BAE06403      767 HRDLAARNILVNAqLICKVSDFGLSRVLee---sSDSTYTTR-GGKIPIRWTAPEAINYrKFTSASDVWSYGIVMWEVMS 842  Ciona intesti...
NP_524625     866 HRDLAARNVLVNAqLICKIADFGLSREIe----nASDAYTTR-GGKIPVRWTAPEAIAFrKFTSASDVWSYGVVLWEVMS 940  fruit fly
BAA81719      657 HRDLAARNILVSKdEVCKVADFGLSRET------TNDEYDVKkGGKIPVRWTAPEAISYrKFTTASDVWSYGVLLWEVMS 730  Ephydatia flu...
BAE06404      846 HRDLAARNVLINNeLVCKVADFGLIRHIg----eKKSTVNTK-GGKISLRWTAPEAVAYqAYSQASDVWSFGVFAWEVIT 920  Ciona intesti...
XP_001196893  511 HRDLAARNILVNEhLVCKVADFGLSRRKe-----LDGAYETR-GGKIPIRWTAPEAIGYkKFTSASDVWSLGVVMWEIMS 584  purple urchin
NP_989691     739 HRDLAARNILVTRsLQCKVSDFGLSRILen---dAEGTYETK-GGKIPIRWTAPEAIAHrIFTSASDVWSFGIVMWEVLS 814  chicken
Feature 1                   #                                                    
1MQB_B        246 YGERPYWELSNHEVMKAINDGFRLPTPMDCPSAIYQLMMQCWQQeRARRPKFADIVSILDKLI 308  human
2GSF_A        246 YGERPYWEMSNQDVIKAVDEGYRLPPPMDCPAALYQLMLDCWQKdRNNRPKFEQIVSILDKLI 308  human
2HEN_A        210 YGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKdRNHRPKFGQIVNTLDKMI 272  house mouse
O61460        926 FGERPYWDWTNQKVISEVMIGYRLPPPMDCPMGLYRIAQWCWKMeRHERPTFTQLLATFHKYI 988  nematode
P21709        822 FGDKPYGEMSNQEVMKSIEDGYRLPPPVDCPAPLYELMKNCWAYdRARRPHFQKLQAHLEQLL 884  human
Q5JZY3        842 FGERPYWDMSGQDVIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKdPGERPRFSQIHSILSKMV 904  human
BAE06403      843 YGERPYWGMSNQDVIHAVGTGYRLPAPMDCPQVQHELMLDCWKKdRNERPKFSQVVATLDRMI 905  Ciona intestinalis
NP_524625     941 YGERPYWNWSNQDVIKSIEKGYRLPAPMDCPEALYQLMLDCWQKqRTHRPTFASIVSTLDNLA 1003 fruit fly
BAA81719      731 YGQQPYEDWDNQMVLDKLESGYRLQKPKDCPSTVYELMQSCWSAeHTDRPTFKELVRLLDAML 793  Ephydatia fluviatilis
BAE06404      921 YGEKPYWSLTNQQVLQAINDGYRLPAPEDCPSVLHQLMLECWHRdKNTRPTFEQVVTRLDAMI 983  Ciona intestinalis
XP_001196893  585 YGERPYWNWPNQDVIKAVEKGYRLPPPMECPEAIHQLMLDCWQRdRNHRPTFTTIVSTLDRLI 647  purple urchin
NP_989691     815 FGDKPYGNMTNQEVMKSLEDGYRLPPPVDCPSILYELMKSCWSHdRMRRPHFQEIRAQLQHFS 877  chicken
2GSF_A        246 YGERPYWEMSNQDVIKAVDEGYRLPPPMDCPAALYQLMLDCWQKdRNNRPKFEQIVSILDKLI 308  human
2HEN_A        210 YGERPYWDMTNQDVINAIEQDYRLPPPMDCPSALHQLMLDCWQKdRNHRPKFGQIVNTLDKMI 272  house mouse
O61460        926 FGERPYWDWTNQKVISEVMIGYRLPPPMDCPMGLYRIAQWCWKMeRHERPTFTQLLATFHKYI 988  nematode
P21709        822 FGDKPYGEMSNQEVMKSIEDGYRLPPPVDCPAPLYELMKNCWAYdRARRPHFQKLQAHLEQLL 884  human
Q5JZY3        842 FGERPYWDMSGQDVIKAVEDGFRLPPPRNCPNLLHRLMLDCWQKdPGERPRFSQIHSILSKMV 904  human
BAE06403      843 YGERPYWGMSNQDVIHAVGTGYRLPAPMDCPQVQHELMLDCWKKdRNERPKFSQVVATLDRMI 905  Ciona intestinalis
NP_524625     941 YGERPYWNWSNQDVIKSIEKGYRLPAPMDCPEALYQLMLDCWQKqRTHRPTFASIVSTLDNLA 1003 fruit fly
BAA81719      731 YGQQPYEDWDNQMVLDKLESGYRLQKPKDCPSTVYELMQSCWSAeHTDRPTFKELVRLLDAML 793  Ephydatia fluviatilis
BAE06404      921 YGEKPYWSLTNQQVLQAINDGYRLPAPEDCPSVLHQLMLECWHRdKNTRPTFEQVVTRLDAMI 983  Ciona intestinalis
XP_001196893  585 YGERPYWNWPNQDVIKAVEKGYRLPPPMECPEAIHQLMLDCWQRdRNHRPTFTTIVSTLDRLI 647  purple urchin
NP_989691     815 FGDKPYGNMTNQEVMKSLEDGYRLPPPVDCPSILYELMKSCWSHdRMRRPHFQEIRAQLQHFS 877  chicken

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