RET

Proto-oncogene tyrosine-protein kinase receptor Ret ;
Cadherin family member 12 ;
Proto-oncogene c-Ret ;
[Cleaved into: Soluble RET kinase fragment ;
Extracellular cell-membrane anchored RET cadherin 120 kDa fragment]

catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ,disease: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. ,disease: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. ,disease: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. ,disease: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. ,disease: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. ,disease: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. ,disease: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. ,disease: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. ,disease:Defects in RET may be a cause of colorectal cancer (CRC) [MIM:114500]. ,function:Probable receptor with tyrosine-protein kinase activity; important for development. ,polymorphism:The Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease. ,PTM:Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. ,PTM:Phosphorylated. ,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. ,similarity:Contains 1 cadherin domain. ,similarity:Contains 1 protein kinase domain. ,subunit:Phosphorylated form interacts with the PBT domain of DOK2 , DOK4 and DOK5. ,

MAPKKK cascade , microtubule cytoskeleton organization , urogenital system development , metanephros development ,ureteric bud development , ameboidal cell migration , neural crest cell migration , kidney development , embryonic epithelial tube formation , morphogenesis of an epithelium , protein amino acid phosphorylation , phosphorus metabolic process , phosphate metabolic process , cell motion , cytoskeleton organization , microtubule-based process , cell adhesion , homophilic cell adhesion , cell surface receptor linked signal transduction , enzyme linked receptor protein signaling pathway , transmembrane receptor protein tyrosine kinase signaling pathway , intracellular signaling cascade ,protein kinase cascade , midgut development , posterior midgut development , mesenchymal cell development , neural crest cell development , neural crest cell differentiation , phosphorylation , morphogenesis of embryonic epithelium , cell-cell adhesion , cell migration , developmental maturation , biological adhesion , neuron differentiation , tube lumen formation , tube morphogenesis , tube development , neuron maturation , cell maturation , autonomic nervous system development , enteric nervous system development , gut development , embryonic morphogenesis , neuron development , tissue morphogenesis , mesenchymal cell differentiation , cell motility , localization of cell , epithelium development , mesenchyme development , epithelial tube morphogenesis ,

Cell membrane ; Single-pass type I membrane protein . Endosome membrane ; Single-pass type I membrane protein . Predominantly located on the plasma membrane. In the presence of SORL1 and GFRA1 , directed to endosomes. .