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
  • RET51
Gene Name
RET
Organism
Humans
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
Functions
ATP binding / calcium ion binding / protein tyrosine kinase activity / receptor activity / transmembrane receptor protein tyrosine kinase activity
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / cellular response to retinoic acid / embryonic epithelial tube formation / enteric nervous system development / homophilic cell adhesion via plasma membrane adhesion molecules / innervation / lymphocyte migration into lymphoid organs / MAPK cascade / membrane protein proteolysis / neural crest cell migration / neuron cell-cell adhesion / neuron maturation / peptidyl-tyrosine phosphorylation / Peyer's patch morphogenesis / positive regulation of cell adhesion mediated by integrin / positive regulation of cell migration / positive regulation of cell size / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of metanephric glomerulus development / positive regulation of neuron maturation / positive regulation of neuron projection development / positive regulation of transcription, DNA-templated / posterior midgut development / protein phosphorylation / regulation of axonogenesis / regulation of cell adhesion / response to drug / response to pain / retina development in camera-type eye / signal transduction / transmembrane receptor protein tyrosine kinase signaling pathway / ureter maturation / ureteric bud development
Components
axon / cytoplasm / dendrite / early endosome / endosome membrane / integral component of plasma membrane / intracellular membrane-bounded organelle / membrane raft / neuronal cell body / plasma membrane / receptor complex
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; 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. 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. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; 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. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.
Pfam Domain Function
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
10q11.2
External Identifiers
ResourceLink
UniProtKB IDP07949
UniProtKB Entry NameRET_HUMAN
GenBank Gene IDX12949
GenAtlas IDRET
HGNC IDHGNC:9967
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12742AmuvatinibinvestigationalunknownDetails
DB018091-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-YlamineexperimentalunknownDetails
DB05294VandetanibapprovedunknownDetails
DB08875Cabozantinibapproved, investigationalyesantagonistDetails
DB08896RegorafenibapprovedyesinhibitorDetails
DB08901Ponatinibapproved, investigationalunknowninhibitorDetails
DB00398Sorafenibapproved, investigationalyesinhibitorDetails
DB09078Lenvatinibapproved, investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails