Proto-oncogene tyrosine-protein kinase receptor ret precursor

Sequence

>sp|P07949|RET_HUMAN Proto-oncogene tyrosine-protein kinase receptor ret OS=Homo sapiens GN=RET PE=1 SV=3 MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAP EEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLT VYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELV AVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFD ADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFA QIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAE LHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPR GIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCY HKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLK QVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDH PDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVY EEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERL FNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAA STPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRA DGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS

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Identifiers

P07949

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Sequence length	1114 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Function	Probable receptor with tyrosine-protein kinase activity; important for development.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Phosphorylated. Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation.
Polymorphism	The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease.
Involvement in disease	Defects in RET may be a cause of colorectal cancer (CRC) [MIM:114500]. Defects in RET are a cause of Hirschsprung disease (HSCR) [MIM:142623]. HSCR is a genetic disorder of neural crest development characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction. Occasionally, MEN2A or FMTC occur in association with HSCR. Defects in RET are the cause of medullary thyroid carcinoma (MTC) [MIM:155240]. MTC is a rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. Defects in RET are the cause of multiple neoplasia type 2B (MEN2B) [MIM:162300]. MEN2B is an uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophtalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. Defects in RET are a cause of pheochromocytoma [MIM:171300]. The pheochromocytomas are catecholamine-producing, chromaffin tumors that arise in the adrenal medulla in 90% of cases. In the remaining 10% of cases, they develop in extra-adrenal sympathetic ganglia and may be referred to as "paraganglioma." Pheochromocytoma usually presents with hypertension. Approximately 10% of pheochromocytoma is hereditary. The genetic basis for most cases of non-syndromic familial pheochromocytoma is unknown. Defects in RET are the cause of multiple neoplasia type 2A (MEN2A) [MIM:171400]; also called multiple neoplasia type 2 (MEN2). MEN2A, the most frequent form of MTC, is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. Chromosomal aberrations involving RET are a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene; inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene; translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene; translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion; translocation t(6;10)(p21.3;q11.2) with RFP generates the Delta RFP/RET oncogene; translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene; translocation t(7;10)(q32;q11) with TIF1 generates the TIF1/RET (PTC6) oncogene. The PTC5 oncogene has been found in 2 cases of PACT in children exposed to radioactive fallout after Chernobyl. Defects in RET are a cause of renal adysplasia [MIM:191830]; also known as renal agenesis or renal aplasia. Renal agenesis refers to the absence of one (unilateral) or both (bilateral) kidneys at birth. Bilateral renal agenesis belongs to a group of perinatally lethal renal diseases, including severe bilateral renal dysplasia, unilateral renal agenesis with contralateral dysplasia and severe obstructive uropathy. Defects in RET are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 1 cadherin domain. Contains 1 protein kinase domain.

Keywords
Cellular component	Membrane
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Disease	Disease mutation Hirschsprung disease Proto-oncogene
Domain	Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	homophilic cell adhesion Inferred from electronic annotation. Source: InterPro posterior midgut development Ref.25 Traceable author statement. Source: ProtInc protein amino acid phosphorylation Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro calcium ion binding Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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Amino acid modifications

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