Proto-oncogene tyrosine-protein kinase receptor Ret
Details
- Name
- Proto-oncogene tyrosine-protein kinase receptor Ret
- Synonyms
- 2.7.10.1
- Cadherin family member 12
- CDHF12
- CDHR16
- Proto-oncogene c-Ret
- PTC
- Gene Name
- RET
- UniProtKB Entry
- P07949Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0004735|Proto-oncogene tyrosine-protein kinase receptor Ret MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAP EEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLT VYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELV AVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFD ADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFA QIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAE LHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPR GIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCY HKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLK QVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDH PDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVY EEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERL FNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAA STPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRA DGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS
- Number of residues
- 1114
- Molecular Weight
- 124317.465
- Theoretical pI
- 6.57
- GO Classification
- Functionssignaling receptor activityProcessesaxon guidance / GDF15-GFRAL signaling pathway / glial cell-derived neurotrophic factor receptor signaling pathway / positive regulation of DNA-templated transcription / positive regulation of gene expression / positive regulation of MAPK cascade / positive regulation of peptidyl-serine phosphorylation of STAT protein / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / response to xenobiotic stimulusComponentsplasma membrane protein complex
- General Function
- Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698)
- Specific Function
- ATP binding
- Pfam Domain Function
- Signal Regions
- 1-28
- Transmembrane Regions
- 636-657
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0021933|Proto-oncogene tyrosine-protein kinase receptor Ret (RET) ATGGCGAAGGCGACGTCCGGTGCCGCGGGGCTGCGTCTGCTGTTGCTGCTGCTGCTGCCG CTGCTAGGCAAAGTGGCATTGGGCCTCTACTTCTCGAGGGATGCTTACTGGGAGAAGCTG TATGTGGACCAGGCGGCCGGCACGCCCTTGCTGTACGTCCATGCCCTGCGGGACGCCCCT GAGGAGGTGCCCAGCTTCCGCCTGGGCCAGCATCTCTACGGCACGTACCGCACACGGCTG CATGAGAACAACTGGATCTGCATCCAGGAGGACACCGGCCTCCTCTACCTTAACCGGAGC CTGGACCATAGCTCCTGGGAGAAGCTCAGTGTCCGCAACCGCGGCTTTCCCCTGCTCACC GTCTACCTCAAGGTCTTCCTGTCACCCACATCCCTTCGTGAGGGCGAGTGCCAGTGGCCA GGCTGTGCCCGCGTATACTTCTCCTTCTTCAACACCTCCTTTCCAGCCTGCAGCTCCCTC AAGCCCCGGGAGCTCTGCTTCCCAGAGACAAGGCCCTCCTTCCGCATTCGGGAGAACCGA CCCCCAGGCACCTTCCACCAGTTCCGCCTGCTGCCTGTGCAGTTCTTGTGCCCCAACATC AGCGTGGCCTACAGGCTCCTGGAGGGTGAGGGTCTGCCCTTCCGCTGCGCCCCGGACAGC CTGGAGGTGAGCACGCGCTGGGCCCTGGACCGCGAGCAGCGGGAGAAGTACGAGCTGGTG GCCGTGTGCACCGTGCACGCCGGCGCGCGCGAGGAGGTGGTGATGGTGCCCTTCCCGGTG ACCGTGTACGACGAGGACGACTCGGCGCCCACCTTCCCCGCGGGCGTCGACACCGCCAGC GCCGTGGTGGAGTTCAAGCGGAAGGAGGACACCGTGGTGGCCACGCTGCGTGTCTTCGAT GCAGACGTGGTACCTGCATCAGGGGAGCTGGTGAGGCGGTACACAAGCACGCTGCTCCCC GGGGACACCTGGGCCCAGCAGACCTTCCGGGTGGAACACTGGCCCAACGAGACCTCGGTC CAGGCCAACGGCAGCTTCGTGCGGGCGACCGTACATGACTATAGGCTGGTTCTCAACCGG AACCTCTCCATCTCGGAGAACCGCACCATGCAGCTGGCGGTGCTGGTCAATGACTCAGAC TTCCAGGGCCCAGGAGCGGGCGTCCTCTTGCTCCACTTCAACGTGTCGGTGCTGCCGGTC AGCCTGCACCTGCCCAGTACCTACTCCCTCTCCGTGAGCAGGAGGGCTCGCCGATTTGCC CAGATCGGGAAAGTCTGTGTGGAAAACTGCCAGGCATTCAGTGGCATCAACGTCCAGTAC AAGCTGCATTCCTCTGGTGCCAACTGCAGCACGCTAGGGGTGGTCACCTCAGCCGAGGAC ACCTCGGGGATCCTGTTTGTGAATGACACCAAGGCCCTGCGGCGGCCCAAGTGTGCCGAA CTTCACTACATGGTGGTGGCCACCGACCAGCAGACCTCTAGGCAGGCCCAGGCCCAGCTG CTTGTAACAGTGGAGGGGTCATATGTGGCCGAGGAGGCGGGCTGCCCCCTGTCCTGTGCA GTCAGCAAGAGACGGCTGGAGTGTGAGGAGTGTGGCGGCCTGGGCTCCCCAACAGGCAGG TGTGAGTGGAGGCAAGGAGATGGCAAAGGGATCACCAGGAACTTCTCCACCTGCTCTCCC AGCACCAAGACCTGCCCCGACGGCCACTGCGATGTTGTGGAGACCCAAGACATCAACATT TGCCCTCAGGACTGCCTCCGGGGCAGCATTGTTGGGGGACACGAGCCTGGGGAGCCCCGG GGGATTAAAGCTGGCTATGGCACCTGCAACTGCTTCCCTGAGGAGGAGAAGTGCTTCTGC GAGCCCGAAGACATCCAGGATCCACTGTGCGACGAGCTGTGCCGCACGGTGATCGCAGCC GCTGTCCTCTTCTCCTTCATCGTCTCGGTGCTGCTGTCTGCCTTCTGCATCCACTGCTAC CACAAGTTTGCCCACAAGCCACCCATCTCCTCAGCTGAGATGACCTTCCGGAGGCCCGCC CAGGCCTTCCCGGTCAGCTACTCCTCTTCCGGTGCCCGCCGGCCCTCGCTGGACTCCATG GAGAACCAGGTCTCCGTGGATGCCTTCAAGATCCTGGAGGATCCAAAGTGGGAATTCCCT CGGAAGAACTTGGTTCTTGGAAAAACTCTAGGAGAAGGCGAATTTGGAAAAGTGGTCAAG GCAACGGCCTTCCATCTGAAAGGCAGAGCAGGGTACACCACGGTGGCCGTGAAGATGCTG AAAGAGAACGCCTCCCCGAGTGAGCTTCGAGACCTGCTGTCAGAGTTCAACGTCCTGAAG CAGGTCAACCACCCACATGTCATCAAATTGTATGGGGCCTGCAGCCAGGATGGCCCGCTC CTCCTCATCGTGGAGTACGCCAAATACGGCTCCCTGCGGGGCTTCCTCCGCGAGAGCCGC AAAGTGGGGCCTGGCTACCTGGGCAGTGGAGGCAGCCGCAACTCCAGCTCCCTGGACCAC CCGGATGAGCGGGCCCTCACCATGGGCGACCTCATCTCATTTGCCTGGCAGATCTCACAG GGGATGCAGTATCTGGCCGAGATGAAGCTCGTTCATCGGGACTTGGCAGCCAGAAACATC CTGGTAGCTGAGGGGCGGAAGATGAAGATTTCGGATTTCGGCTTGTCCCGAGATGTTTAT GAAGAGGATTCCTACGTGAAGAGGAGCCAGGGTCGGATTCCAGTTAAATGGATGGCAATT GAATCCCTTTTTGATCATATCTACACCACGCAAAGTGATGTATGGTCTTTTGGTGTCCTG CTGTGGGAGATCGTGACCCTAGGGGGAAACCCCTATCCTGGGATTCCTCCTGAGCGGCTC TTCAACCTTCTGAAGACCGGCCACCGGATGGAGAGGCCAGACAACTGCAGCGAGGAGATG TACCGCCTGATGCTGCAATGCTGGAAGCAGGAGCCGGACAAAAGGCCGGTGTTTGCGGAC ATCAGCAAAGACCTGGAGAAGATGATGGTTAAGAGGAGAGACTACTTGGACCTTGCGGCG TCCACTCCATCTGACTCCCTGATTTATGACGACGGCCTCTCAGAGGAGGAGACACCGCTG GTGGACTGTAATAATGCCCCCCTCCCTCGAGCCCTCCCTTCCACATGGATTGAAAACAAA CTCTATGGTAGAATTTCCCATGCATTTACTAGATTCTAG
- Chromosome Location
- 10
- Locus
- 10q11.21
- External Identifiers
Resource Link UniProtKB ID P07949 UniProtKB Entry Name RET_HUMAN GenBank Gene ID X12949 GeneCard ID RET GenAtlas ID RET HGNC ID HGNC:9967 PDB ID(s) 2IVS, 2IVT, 2IVU, 2IVV, 2X2K, 2X2L, 2X2M, 2X2U, 4CKI, 4CKJ, 4UX8, 5AMN, 5FM2, 5FM3, 6FEK, 6GL7, 6I82, 6I83, 6NE7, 6NEC, 6NJA, 6Q2J, 6Q2N, 6Q2O, 6Q2R, 6Q2S, 6VHG, 7DU8, 7DU9, 7DUA, 7JU5, 7JU6, 7NZN, 7RUN KEGG ID hsa:5979 IUPHAR/Guide To Pharmacology ID 2185 NCBI Gene ID 5979 - General References
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Associated Data
- Bio-Entities
Bio-Entity Type Proto-oncogene tyrosine-protein kinase receptor Ret (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Imatinib approved yes target inhibitor Details Amuvatinib investigational unknown target Details XL999 investigational unknown target Details 1-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine experimental unknown target Details Vandetanib approved yes target inhibitor Details Cabozantinib approved, investigational yes target antagonist Details Regorafenib approved yes target inhibitor Details Ponatinib approved, investigational unknown target inhibitor Details Sorafenib approved, investigational yes target inhibitor Details Lenvatinib approved, investigational yes target inhibitor Details Fostamatinib approved, investigational unknown target inhibitor Details Erdafitinib approved, investigational unknown target substrate Details Selpercatinib approved, investigational yes target inhibitor Details Pralsetinib approved, investigational yes target inhibitor Details Sitravatinib investigational yes target inhibitor Details Tamatinib experimental, investigational yes target inhibitor Details Agerafenib investigational yes target inhibitor Details Semaxanib investigational yes target inhibitor Details