2IVV,2IVT


Conserved Protein Domain Family
PTKc_RET

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cd05045: PTKc_RET 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 173631
View PSSM: cd05045
Aligned: 6 rows
Threshold Bit Score: 558.425
Threshold Setting Gi: 8919858
Created: 15-Aug-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 13 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:2IVT; Human RET tyr kinase binds AMP; defined at 4A contacts.
    View structure with Cn3D
  • Structure:2IVV; Human RET tyr kinase binds inhibitor, Pp1; defined at 4A contacts.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             ####    #                 # #                                            
2IVV_A      24 NLVLGKTLGEGEFGKVVKATAFhlkgraGYTTVAVKMLKENaspseLRDLLSEFNVLKQVNHPHVIKLYGACSqdGPLLL 103  human
2IVT_A      24 NLVLGKTLGEGEFGKVVKATAFhlkgraGYTTVAVKMLKENaspseLRDLLSEFNVLKQVNHPHVIKLYGACSqdGPLLL 103  human
CAA90078   715 NLVLGKTLGEGEFGKVVKATAFrlkgraGYTTVAVKMLKENasqseLRDLLSEFNLLKQVNHPHVIKLYGACSqdGPLYL 794  chicken
CAA64146   715 NLVLGKTLGEGEFGKVVKATAFrlkgkaGYTTVAVKMLKENashseLRDLLSEFTLLKQVNHPHVIKMYGACSqdGPLYL 794  zebrafish
AAG00544   710 NLVLGKTLGEGEFGKVVKATAFrlkgkaGYTTVAVKMLKESasqseLRDLLSEFNLLKQVNHPHVIKLYGACTqdGPLHL 789  African clawed frog
8919858    770 KLQLDTVLGEGEFGQVLKGFATeiaglpGITTVAVKMLKKGsnsveYMALLSEFQLLQEVSHPNVIKLLGACTssEAPLL 849  fruit fly
Feature 1       ## #   #                                                                     # 
2IVV_A     104 IVEYAKYGSLRGFLRESRKVGpgylgsggsrnsssldhpDERALTMGDLISFAWQISQGMQYLAEMSLVHRDLAARNILV 183  human
2IVT_A     104 IVEYAKYGSLRGFLRESRKVGpgylgsggsrnsssldhpDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILV 183  human
CAA90078   795 IVEYAKYGSLRSFLRESRKVGpsyvgsdgnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 874  chicken
CAA64146   795 IVEYAKYGSLRNFLRESRKVGpsymgndanrnssylenpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 874  zebrafish
AAG00544   790 IVEYSKYGSLRSFLRESRKVGpstlggdsnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 869  African clawed frog
8919858    850 IIEYARYGSLRSYLRLSRKIEcagv----------dfadGVEPVNVKMVLTFAWQICKGMAYLSELKLVHRDLAARNVLL 919  fruit fly
Feature 1               #                                                                      
2IVV_A     184 AEgRKMKISDFGLSRDVYEEDSXVKRSQGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFN 263  human
2IVT_A     184 AEgRKMKISDFGLSRDVYEEDSXVKRSQGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFN 263  human
CAA90078   875 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 954  chicken
CAA64146   875 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMATESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 954  zebrafish
AAG00544   870 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 949  African clawed frog
8919858    920 ADgKICKISDFGLTRDVYEDDAYLKRSRDRVPVKWMAPESLADhVYTSKSDVWSFGVLCWELITLGASPYPGIAPQNLWS 999  fruit fly
Feature 1                                                        
2IVV_A     264 LLKTGHRMERPDNcSEEMYRLMLQCWKQePDKRPVFADISKDLEKMMVKR 313  human
2IVT_A     264 LLKTGHRMERPDNcSEEMYRLMLQCWKQePDKRPVFADISKDLEKMMVKR 313  human
CAA90078   955 LLKTGYRMERPENcSEEMYNLMLRCWKQePDKRPTFAEISKELEKMMVKS 1004 chicken
CAA64146   955 LLKTGYRMEKPENcTDEMYNLMLRCWKQeSDKRPTFSDISKELEKMMVKS 1004 zebrafish
AAG00544   950 LLKTGYRMEKPENcSDEMYNLMLKCWKQePEKRQTFGEISKELEKMMVKS 999  African clawed frog
8919858   1000 LLKTGYRMDRPENcSEAVYSIVRTCWADePNGRPSFKFLASEFEKLLGNN 1049 fruit fly

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