2IVV,2IVT


Conserved Protein Domain Family
PTKc_RET

?
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
?
PSSM-Id: 173631
View PSSM: cd05045
Aligned: 6 rows
Threshold Bit Score: 558.425
Threshold Setting Gi: 8919858
Created: 15-Aug-2006
Updated: 2-Mar-2014
Structure
?
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
?
Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              ####    #                 # #                                            
2IVV_A       24 NLVLGKTLGEGEFGKVVKATAFhlkgraGYTTVAVKMLKENaspseLRDLLSEFNVLKQVNHPHVIKLYGACSqdGPLLL 103
2IVT_A       24 NLVLGKTLGEGEFGKVVKATAFhlkgraGYTTVAVKMLKENaspseLRDLLSEFNVLKQVNHPHVIKLYGACSqdGPLLL 103
gi 871042   715 NLVLGKTLGEGEFGKVVKATAFrlkgraGYTTVAVKMLKENasqseLRDLLSEFNLLKQVNHPHVIKLYGACSqdGPLYL 794
gi 2102660  715 NLVLGKTLGEGEFGKVVKATAFrlkgkaGYTTVAVKMLKENashseLRDLLSEFTLLKQVNHPHVIKMYGACSqdGPLYL 794
gi 9837361  710 NLVLGKTLGEGEFGKVVKATAFrlkgkaGYTTVAVKMLKESasqseLRDLLSEFNLLKQVNHPHVIKLYGACTqdGPLHL 789
gi 8919858  770 KLQLDTVLGEGEFGQVLKGFATeiaglpGITTVAVKMLKKGsnsveYMALLSEFQLLQEVSHPNVIKLLGACTssEAPLL 849
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ## #   #                                                                     # 
2IVV_A      104 IVEYAKYGSLRGFLRESRKVGpgylgsggsrnsssldhpDERALTMGDLISFAWQISQGMQYLAEMSLVHRDLAARNILV 183
2IVT_A      104 IVEYAKYGSLRGFLRESRKVGpgylgsggsrnsssldhpDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILV 183
gi 871042   795 IVEYAKYGSLRSFLRESRKVGpsyvgsdgnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 874
gi 2102660  795 IVEYAKYGSLRNFLRESRKVGpsymgndanrnssylenpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 874
gi 9837361  790 IVEYSKYGSLRSFLRESRKVGpstlggdsnrnssyldnpDERALTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLV 869
gi 8919858  850 IIEYARYGSLRSYLRLSRKIEcagv----------dfadGVEPVNVKMVLTFAWQICKGMAYLSELKLVHRDLAARNVLL 919
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                #                                                                      
2IVV_A      184 AEgRKMKISDFGLSRDVYEEDSXVKRSQGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFN 263
2IVT_A      184 AEgRKMKISDFGLSRDVYEEDSXVKRSQGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFN 263
gi 871042   875 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 954
gi 2102660  875 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMATESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 954
gi 9837361  870 AEgRKMKISDFGLSRDVYEEDSYVKRSKGRIPVKWMAIESLFDhIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFN 949
gi 8919858  920 ADgKICKISDFGLTRDVYEDDAYLKRSRDRVPVKWMAPESLADhVYTSKSDVWSFGVLCWELITLGASPYPGIAPQNLWS 999
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
Feature 1                                                         
2IVV_A      264 LLKTGHRMERPDNcSEEMYRLMLQCWKQePDKRPVFADISKDLEKMMVKR 313
2IVT_A      264 LLKTGHRMERPDNcSEEMYRLMLQCWKQePDKRPVFADISKDLEKMMVKR 313
gi 871042   955 LLKTGYRMERPENcSEEMYNLMLRCWKQePDKRPTFAEISKELEKMMVKS 1004
gi 2102660  955 LLKTGYRMEKPENcTDEMYNLMLRCWKQeSDKRPTFSDISKELEKMMVKS 1004
gi 9837361  950 LLKTGYRMEKPENcSDEMYNLMLKCWKQePEKRQTFGEISKELEKMMVKS 999
gi 8919858 1000 LLKTGYRMDRPENcSEAVYSIVRTCWADePNGRPSFKFLASEFEKLLGNN 1049

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