1MQB


Conserved Protein Domain Family
PTKc_EphR_A2

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cd05063: PTKc_EphR_A2 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. 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. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 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).
Statistics
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PSSM-Id: 133194
View PSSM: cd05063
Aligned: 4 rows
Threshold Bit Score: 590.407
Threshold Setting Gi: 37926808
Created: 17-May-2007
Updated: 2-Oct-2020
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:includes ATP binding and substrate binding sites
  • Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs, and the structures of Eph receptors bound with ATP analogs.
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 # ###   #                # #                                        
1MQB_B     40 EIHPSCVTRQKVIGAGEFGEVYKGMLKtssGKKEVPVAIKTLKAGYTEkQRVDFLGEAGIMGQFSHHNIIRLEGVISKyk 119  human
AAH89174  595 EISPNSITRQKVIGAGEFGEVFKGILKl-pGKKESTVAIKTLKAGYTEkQRNDFLSEASIMGQFCHHNIIRLEGVVSKyk 673  African clawed frog
NP_571490 615 EIHPGHITKQKVIGAGEFGEVFRGSLKm-pGRSEVAVAIKTLKPGYTEkQRQDFLSEASIMGQFSHKNIIRLEGVVTKfk 693  zebrafish
CAG01742  346 EIHPSHIAKEKVIGAGEFGEVYRGILKv-pGRKESAVAIKTLKPGYTEkQRQDFLSEASIMGQFAHQNIIRLEGVVTKfk 424  Tetraodon nigrovi...
Feature 1          ## #                                           #   ## #          #         
1MQB_B    120 PMMIITEYMENGALDKFLREKdgeFSVLQLVGMLRGIAAGMKYLANMNYVHRDLAARNILVNSnLVCKVSDFGLSRVLED 199  human
AAH89174  674 PMMIVTEHMENGALDKFLKDNdgeFSPIQLVGMLRGIAAGMKYLSEMNYVHRDLAARNILVNSqLVCKVSDFGLSRVLED 753  African clawed frog
NP_571490 694 DAMIITEYMENGALDQYLRDHdgdFSSYQLVGMLNGIAAGMKYLSDMNYVHRDLAARNVLVNSnLECKVSDFGLSRVLED 773  zebrafish
CAG01742  425 HAMIITEYMENGALDRYLRDHdgeFTSFQLVGMLRGIAAGMKYLSDMSYVHRDLAARNILVNNtLECKVSDFGLSRVLED 504  Tetraodon nigrovi...
Feature 1              #####        #                                 #                       
1MQB_B    200 DPEATYTTSGGKIPIRWTAPEAISYrKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPMDCPSAI 279  human
AAH89174  754 DPEATYTTSGGKIPIRWTAPEAISYrKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQEVMKAINEGFRLPAPMDCPSAI 833  African clawed frog
NP_571490 774 FPEGTYTTTGGKIPIRWTAPEAIAYrKFTSASDVWSFGIVMWEVMSFGERPYWDMSNQEVMKSINDGYRLPAPMGCPSAV 853  zebrafish
CAG01742  505 DPEGTYTTSGGKIPIRWTAPEAIAYrKFASASDVWSFGIVMWEVMAFGERPYWDMSNHEVMKAINEAFRLPAPMDCPSAV 584  Tetraodon nigrovi...
Feature 1                                  
1MQB_B    280 YQLMMQCWQQeRARRPKFADIVSILDKLI 308  human
AAH89174  834 YQLMMQCWQQeRNRRPKFPDIVSILDKLI 862  African clawed frog
NP_571490 854 NQLMLQCWMQdRSTRPRFVDIVNLLEKLL 882  zebrafish
CAG01742  585 YQLMLQCWLHdRAKRPRFGDIVNLLDKLL 613  Tetraodon nigroviridis

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