1M17,1XKK,2GS7,2GS6


Conserved Protein Domain Family
PTKc_EGFR

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cd05108: PTKc_EGFR (this model, PSSM-Id:173654 is obsolete and has been replaced by 270683)
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor
Protein Tyrosine Kinase (PTK) family; Epidermal Growth Factor Receptor (EGFR); 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. EGFR (HER1, ErbB1) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor tyr kinases (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other tyr kinases, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder.
Statistics
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Aligned: 8 rows
Threshold Bit Score: 653.215
Threshold Setting Gi: 18266816
Created: 8-Jun-2007
Updated: 17-Jan-2013
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:active site [active site]
Evidence:
  • Structure:2GS6_A; Human EGFR tyr kinase binds ATP analog and peptide substrate; defined at 3.5A contacts.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    ##  ##                     #                                      
1M17_A      15 LRILKETEFKKIKVLGSGAFGTVYKGLWIPegekVKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLt 94   human
1XKK_A      34 LRILKETEFKKIKVLGSGAFGTVYKGLWIPegekVKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLt 113  human
2GS7_A      12 LRILKETEFKKIKVLGSGAFGTVYKGLWIPegekVKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLt 91   human
2GS6_A      12 LRILKETEFKKIKVLGSGAFGTVYKGLWIPegekVKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLt 91   human
NP_919405  703 LRILKETEFKKIKVLGSGAFGTVHKGLWVPegenVKIPVAIKVLREATspKANKEIMDEAYVMASVEHPHVCRLLGICLt 782  zebrafish
TVCHLV     713 LRILKETEFKKVKVLGSGAFGTVYKGLWIPegekVKIPVAIKELREATspKANKEILDEAYVMASVDNPHVCRLLGICLt 792  chicken
ABG35749   289 LRILKETEFKKIKVLGSGAFGTVYQGLWIPegegIKIPVAIKELREATspKANKEILDEAYVMASVENPYVCRLLGICLt 368  African clawed frog
P13388     702 LRILKETEFKKDRVLGSGAFGTVYKGLWNPdgenIRIPVAIKVLREATspKVNQEVLDEAYVMASVDHPHVCRLLGICLt 781  southern platyfish
Feature 1             # #   #                                           ##            #        
1M17_A      95 sTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTpQHVKITDFGLAKLLG 174  human
1XKK_A     114 sTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTpQHVKITDFGLAKLLG 193  human
2GS7_A      92 sTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTpQHVKITDFGLAKLLG 171  human
2GS6_A      92 sTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTpQHVKITDFGLAKLLG 171  human
NP_919405  783 sTVQLITQLMPYGCLLDYVRENKDRIGSQHLLNWCVQIAKGMNYLEERHLVHRDLAARNVLVKTpQHVKITDFGLAKLLN 862  zebrafish
TVCHLV     793 sTVQLITQLMPYGCLLDYIREHKDNIGSQYLLNWCVQIAKGMNYLEERRLVHRDLAARNVLVKTpQHVKITDFGLAKLLG 872  chicken
ABG35749   369 sTVQLITQLMPFGCLLDYVRENKDNIGSRHLLNWCVQIAKGMNYLEERRLVHRDLAARNVLVKGpQHVKITDFGLAKLLG 448  African clawed frog
P13388     782 sAVQLVTQLMPYGCLLDYVRQHQERICGQWLLNWCVQIAKGMNYLEERHLVHRDLAARNVLLKNpNHVKITDFGLSKLLT 861  southern platyfish
Feature 1                  #####    #   #                                                      
1M17_A     175 AEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 254  human
1XKK_A     194 AEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 273  human
2GS7_A     172 AEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 251  human
2GS6_A     172 AEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 251  human
NP_919405  863 ADEKEYHADGGKVPIKWMALESIQHRTYTHQSDVWSYGVTVWELMTFGTKPYDGIPASEIAGVLEKGERLPQPPICTIDV 942  zebrafish
TVCHLV     873 ADEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSVLEKGERLPQPPICTIDV 952  chicken
ABG35749   449 ADEKAYHAEGGKVPIKWMALESILHRTYTHQSDVWSYGVTVWELMTFGLKPYDGIPASEISNILEKGERLPQPPICTIDV 528  African clawed frog
P13388     862 ADEKEYQADGGKVPIKWMALESILQWTYTHQSDVWSYGVTVWELMTFGSKPYDGIPAKEIASVLENGERLPQPPICTIEV 941  southern platyfish
Feature 1                                                                                  
1M17_A     255 YMIMVKCWMIdADSRPKFRELIIEFSKMARDPQRYLVIQGdermhlpsptdsnfyralmdeeDMDDVVDADEYLIP 330  human
1XKK_A     274 YMIMVKCWMIdADSRPKFRELIIEFSKMARDPQRYLVIQGdermhlpsptdsnfyralmdeeDMDDVVDADEYLIP 349  human
2GS7_A     252 YMIMRKCWMIdADSRPKFRELIIEFSKMARDPQRYLVIQGdermhlpsptdsnfyralmdeeDMDDVVDADEYLIP 327  human
2GS6_A     252 YMIMVKCWMIdADSRPKFRELIIEFSKMARDPQRYLVIQGdermhlpsptdsnfyralmdeeDMDDVVDADEYLIP 327  human
NP_919405  943 YMIMVKCWMIdAESRPRFRELIAEFTKMARDPSRYLVIQGddrmhlpspsd-skfyrslmsgELDEAVDADEYLVP 1017 zebrafish
TVCHLV     953 YMIMVKCWMIdADSRPKFRELIAEFSKMARDPPRYLVIQGdermhlpsptdskfyrtlmeeeDMEDIVDADEYLVP 1028 chicken
ABG35749   529 YMIMVKCWMIdAESRPKFRELSAEFTKMARDPTRYLVIQGddrmhlpspve-skihpalveaGLGDIVDAEEYLLP 603  African clawed frog
P13388     942 YMIILKCWMIdPSSRPRFRELVGEFSQMARDPSRYLVIQGnlpslsdr------rlfsrllsSDDDVVDADEYLLP 1011 southern platyfish

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