3KEX,3LMG


Conserved Protein Domain Family
PTK_HER3

?
cd05111: PTK_HER3 
Click on image for an interactive view with Cn3D
Pseudokinase domain of the Protein Tyrosine Kinase, HER3
HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (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 PTKs, 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. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
?
PSSM-Id: 173656
View PSSM: cd05111
Aligned: 5 rows
Threshold Bit Score: 608.108
Threshold Setting Gi: 281500900
Created: 8-Jun-2007
Updated: 2-Oct-2020
Structure
?
Program:
Drawing:
Aligned Rows:
 
ATP binding
Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3KEX; Human HER3 binds ATP; contacts at 4A.
    View structure with Cn3D
  • Comment:Though inactive to exogenous peptides, HER3 is still able to bind ATP and is capable of autophosphorylation.
  • Structure:3LMG; Human HER3 binds AMP-PNP; contacts at 4A.
    View structure with Cn3D

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                       ##### # #                # #                                      
3KEX_A          7 ARIFKETELRKLKVLGSGVFGTVHKGVWIPegesIKIPVCIKVIEDKSgrQSFQAVTDHMLAIGSLDHAHIVRLLGLCPg 86   human
NP_001005320  651 ARILRTSELKKIKLLGSGVFGTVHKGIWIPegdtVKIPVAIKTIQDRTgrQTFQEITDHMLAMGSLDHAYIVRILGICPg 730  zebrafish
NP_001038134  702 ARIFKETELKRLKVLGSGVFGTVHKGIWIPdgdsIKIPVSIKVIQDWSgqQSFHAVTDHMLAIGSLDHAYIVRLLGICPg 781  chicken
NP_001014826  702 ARILKPQELRKGKLLGYGVFGTVNKGFWIPegdsLKIPVAIKTIQNRSsrQTFTEITDHMLSMGSLDHPYIVRLIGICPg 781  zebrafish
3LMG_A         25 ARIFKETELRKLKVLGSGVFGTVHKGVWIPegesIKIPVCIKVIEDKSgrQSFQAVTDHMLAIGSLDHAHIVRLLGLCPg 104  human
Feature 1               ####                                           #   ## #          #        
3KEX_A         87 sSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSpSQVQVADFGVADLLP 166  human
NP_001005320  731 aSLQLVTQLSPQGSLLEHIRQRRDNLNPQRLLNWCVQIAKGMYYLEEQRMVHRNLAARNILLKSdLIVQIADYGIADLLY 810  zebrafish
NP_001038134  782 pQLQLVTQLLPLGSLLDYVRKNRGSISPQLLLNWCVQVAKGMYYLEEHRMVHRNLAARNVLLKSpSQAQVADFGIADLLY 861  chicken
NP_001014826  782 aSLQLITQLSPHGSLLQHLRQHKDSLDPQRLLNWCVQIAKGMYYLEEHCMAHRNLAARNILLKSdYIVQISDFGVADLLY 861  zebrafish
3LMG_A        105 sSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNVLLKSpSQVQVADFGVADLLP 184  human
Feature 1                                                                                         
3KEX_A        167 PDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDV 246  human
NP_001005320  811 PDDKKYFFNEIKTPIKWMALESILFRRYTHQSDVWSYGVTVWEMMSYGAEPYSAMRPQEVPDLLEKGERLSQPQICTIDV 890  zebrafish
NP_001038134  862 PDDKKYFYNEVKTPIKWMALESIHFGKYTHQSDVWSYGVTLWEMMTFGAEPYAGIRLPEVPDLLEKGERLPQPHICTIDV 941  chicken
NP_001014826  862 PDDKKYVYSEHKTSIKWMALESILFGRYTHQSDVWSYGVTVWEMMSYGAEPYASMHPHDVPGLLEKGERLAQPQICTIDV 941  zebrafish
3LMG_A        185 PDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDV 264  human
Feature 1                                                
3KEX_A        247 YMVMVKCWMIdENIRPTFKELANEFTRMARDPPRYLVIK 285  human
NP_001005320  891 YMVMVKCWMIdENVRPTFKELANEFTRMARDPHRYLVIK 929  zebrafish
NP_001038134  942 YMVMVKCWMIdENIRPTFKELANEFTRMARDPPRYLVIK 980  chicken
NP_001014826  942 YMVMVKCWMIdENVRPTFKELASEFTRMARDPPRYLVVR 980  zebrafish
3LMG_A        265 YMVMVKCWMIdENIRPTFKELANEFTRMARDPPRYLVIK 303  human

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap