Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Ret. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene, a member of the cadherin superfamily, encodes one of the receptor tyrosine kinases, which are cell-surface molecules that transduce signals for cell growth and differentiation. This gene plays a crucial role in neural crest development, and it can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Mutations in this gene are associated with the disorders multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, Hirschsprung disease, and medullary thyroid carcinoma. Two transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their biological validity has not been confirmed. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Ret
  • participates in the following biological processes:
    • embryonic epithelial tube formation ^[12]
    • neuron cell-cell adhesion ^[6]
• The gene product of Ret has been shown to bind to the gene products of Epha5, Gfra3. ^{[3, 4, 12, 14]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Ret
  • participates in the following biological processes:
    • enteric nervous system development ^[10]
    • nervous system development ^[11]
    • neural crest cell migration ^[15]
    • neuron maturation ^[5]
    • Peyer's patch morphogenesis ^[13]
    • positive regulation of metanephric glomerulus development ^[8]
    • positive regulation of transcription, DNA-dependent ^[8]
    • response to pain ^[9]
    • ureter maturation ^[7]
    • ureteric bud development ^[2]
• Researchers have inferred, based on genetic interactions, that the gene product of Ret
  • participates in the following biological processes:
    • embryonic epithelial tube formation based on interactions with Shank3 ^[12]
    • MAPK cascade based on interactions with Shank3 ^[12]
    • transmembrane receptor protein tyrosine kinase signaling pathway based on interactions with Gfra2, Nrtn ^[1]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Ret:
  • participates in the following biological processes:
    • cellular response to retinoic acid
    • innervation
    • membrane protein proteolysis
    • neuron cell-cell adhesion
    • positive regulation of cell adhesion mediated by integrin
    • positive regulation of cell migration
    • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
    • positive regulation of neuron maturation
    • positive regulation of neuron projection development
    • regulation of cell adhesion
  • performs the following molecular functions:
    • calcium ion binding
  • is located in the following cellular components:
    • endosome membrane
    • integral to plasma membrane
    • membrane raft

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Summary text based on GO annotations supported by structural data

• Ret encodes a protein or proteins that contain the following InterPro domains: Cadherin, Cadherin-like, Protein kinase, ATP binding site, Protein kinase, catalytic domain, Protein kinase-like domain, Serine-threonine/tyrosine-protein kinase catalytic domain, Tyrosine-protein kinase, active site, Tyrosine-protein kinase, catalytic domain, Tyrosine-protein kinase, Ret receptor, indicating that the gene product:
  • participates in the following biological processes:
    • homophilic cell adhesion
  • performs the following molecular functions:
    • ATP binding
    • protein kinase activity
    • protein tyrosine kinase activity
    • transferase activity, transferring phosphorus-containing groups
  • is located in the following cellular components:
    • membrane

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Ret indicates that it:
  • participates in the following biological processes:
    • cell adhesion
    • phosphorylation
  • performs the following molecular functions:
    • ATP binding
    • kinase activity
    • nucleotide binding
    • protein tyrosine kinase activity
    • transferase activity
  • is located in the following cellular components:
    • endosome
    • integral to membrane
    • membrane
    • plasma membrane

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References

1. Baloh RH et al. (1998) GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family. Proc Natl Acad Sci U S A, 95:5801-6. (PubMed:9576965)
2. Batourina E et al. (2002) Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat Genet, 32:109-15. (PubMed:12195422)
3. Bolon B et al. (2004) The candidate neuroprotective agent artemin induces autonomic neural dysplasia without preventing peripheral nerve dysfunction. Toxicol Pathol, 32:275-94. (PubMed:15204970)
4. Bonanomi D et al. (2012) Ret Is a Multifunctional Coreceptor that Integrates Diffusible- and Contact-Axon Guidance Signals. Cell, 148:568-82. (PubMed:22304922)
5. Burau K et al. (2004) c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice. Eur J Neurosci, 20:353-62. (PubMed:15233745)
6. Cabrera JR et al. (2011) RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. J Biol Chem, 286:14628-38. (PubMed:21357690)
7. Chia I et al. (2011) Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a Gata3-Raldh2-Ret molecular network in mice. Development, 138:2089-97. (PubMed:21521737)
8. Clarke JC et al. (2006) Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage. Hum Mol Genet, 15:3420-8. (PubMed:17047028)
9. Golden JP et al. (2010) RET signaling is required for survival and normal function of nonpeptidergic nociceptors. J Neurosci, 30:3983-94. (PubMed:20237269)
10. Natarajan D et al. (1999) Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture. Development, 126:157-68. (PubMed:9834195)
11. Rossi J et al. (2000) Distinct roles for GFRalpha1 and GFRalpha2 signalling in different cranial parasympathetic ganglia in vivo. Eur J Neurosci, 12:3944-52. (PubMed:11069590)
12. Schuetz G et al. (2004) The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J Cell Biol, 167:945-52. (PubMed:15569713)
13. Veiga-Fernandes H et al. (2007) Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature, 446:547-51. (PubMed:17322904)
14. Worby CA et al. (1998) Identification and characterization of GFRalpha-3, a novel Co-receptor belonging to the glial cell line-derived neurotrophic receptor family. J Biol Chem, 273:3502-8. (PubMed:9452475)
15. Yan H et al. (2004) Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent. Dev Biol, 272:118-33. (PubMed:15242795)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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