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proto-oncogene tyrosine-protein kinase receptor ret; C-ret; (RET, CDHF12)

Function: - receptor tyrosine kinase - functional receptor for GDNFR-alpha - role in development - phosphorylated form interacts with the PBT domain of DOK2, DOK4 & DOK5 (putative) - phosphorylated - autophosphorylated on C-terminal Tyr upon ligand stimulation Structure: - belongs to the protein kinase superfamily, Tyr protein kinase family - contains 1 cadherin domain - contains 1 protein kinase domain Compartment: membrane Polymorphism: - the Cys-982 polymorphism may be associated with an increased risk for developing Hirschsprung disease Pathology: 1) defects in RET may cause a) colorectal cancer b) Hirschsprung disease c) medullary thyroid carcinoma d) multiple endocrine neoplasia type-2B (MEN2B) e) pheochromocytoma f) multiple endocrine neoplasia type-2A (MEN2A) g) renal aplasia h) congenital central hypoventilation syndrome (CCHS) 2) chromosomal aberrations involving RET are a cause of thyroid papillary carcinoma (PACT) [MIM:188550] a) inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene b) inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3)oncogene c) translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene; may occur secondary to radiation exposure d) translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion e) translocation t(6;10)(p21.3;q11.2) with RFP generates the delta RFP/RET oncogene f) translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene g) translocation t(7;10)(q32;q11) with TIF1 generates the TIF1/RET (PTC6) oncogene

Related

ret proto-oncogene

General

oligomerizing protein proto oncogene protein tyrosine kinase receptor (RTK)

Properties

SIZE: entity length = 1114 aa MW = 124 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-28} N-glycosylation site {N98} N-glycosylation site {N151} cadherin domain {168-272} MOTIF: N-glycosylation site {N199} N-glycosylation site {N336} N-glycosylation site {N343} N-glycosylation site {N361} N-glycosylation site {N367} N-glycosylation site {N377} N-glycosylation site {N394} N-glycosylation site {N448} N-glycosylation site {N468} N-glycosylation site {N554} transmembrane domain {636-657} breakpoint {712-713} kinase domain SITE: 724-1016 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 730-738 ATP-binding site NAME: ATP-binding site SITE: 758-758 Tyr phosphorylation site {Y806} Tyr phosphorylation site {Y809} aspartate residue {D874} Tyr phosphorylation site {Y900} Tyr phosphorylation site {Y905} Tyr phosphorylation site {Y981} Tyr phosphorylation site {Y1015} Tyr phosphorylation site {Y1062} Tyr phosphorylation site {Y1090} Tyr phosphorylation site {Y1096}

Database Correlations

OMIM correlations MORBIDMAP 164761 UniProt P07949 PFAM correlations Kegg hsa:5979 ENZYME 2.7.10.1

References

  1. UniProt :accession P07949
  2. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/RETID76.html
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=RET
  4. MEN2 RET database http://www.arup.utah.edu/database/MEN2/MEN2_welcome.php
  5. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249-70. Review. PMID: 1988147
  6. van Heyningen V. Genetics. One gene-four syndromes. Nature. 1994 Jan 27;367(6461):319-20. PMID: 7906865
  7. Romeo G et al. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature. 1994 Jan 27;367(6461):377-8. PMID: 8114938
  8. Trupp M et al. Functional receptor for GDNF encoded by the c-ret proto- oncogene. Nature. 1996 Jun 27;381(6585):785-9. PMID: 8657281

Component-of

glial derived neurotrophic factor [GDNF] receptor