ID:RET_MOUSE DESCRIPTION: RecName: Full=Proto-oncogene tyrosine-protein kinase receptor Ret; EC=2.7.10.1; AltName: Full=Proto-oncogene c-Ret; Contains: RecName: Full=Soluble RET kinase fragment; Contains: RecName: Full=Extracellular cell-membrane anchored RET cadherin 120 kDa fragment; Flags: Precursor; 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Repressed by withaferin A (WA). SUBUNIT: Interacts (not phosphorylated) with CC PTK2/FAK1 (via FERM domain). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas. Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex (By similarity). Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5. The phosphorylated form interacts with PLCG1 and GRB7. Binds to ARTN. INTERACTION: Q60629:Epha5; NbExp=5; IntAct=EBI-5548911, EBI-1267609; SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein (By similarity). TISSUE SPECIFICITY: Expressed in peripheral nerve cells and hematopoietic cells. PTM: Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. Dephosphorylated by PTPRJ on Tyr-906, Tyr-1016 and Tyr-1063 (By similarity). PTM: Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell- membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons (By similarity). DISRUPTION PHENOTYPE: Exclusive loss in nociceptors results in a reduction in nociceptor number and size with a reduced epidermal innervation, but increased sensitivity to cold and increased formalin-induced pain. MISCELLANEOUS: Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC). SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SIMILARITY: Contains 1 cadherin domain. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P35546
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0000187 activation of MAPK activity GO:0001657 ureteric bud development GO:0001755 neural crest cell migration GO:0001838 embryonic epithelial tube formation GO:0006468 protein phosphorylation GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007155 cell adhesion GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules GO:0007158 neuron cell-cell adhesion GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007399 nervous system development GO:0009653 anatomical structure morphogenesis GO:0010628 positive regulation of gene expression GO:0010976 positive regulation of neuron projection development GO:0014042 positive regulation of neuron maturation GO:0016310 phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0030155 regulation of cell adhesion GO:0030182 neuron differentiation GO:0030335 positive regulation of cell migration GO:0033141 positive regulation of peptidyl-serine phosphorylation of STAT protein GO:0033619 membrane protein proteolysis GO:0033630 positive regulation of cell adhesion mediated by integrin GO:0035799 ureter maturation GO:0035860 glial cell-derived neurotrophic factor receptor signaling pathway GO:0042493 response to drug GO:0042551 neuron maturation GO:0043410 positive regulation of MAPK cascade GO:0045793 positive regulation of cell size GO:0045893 positive regulation of transcription, DNA-templated GO:0048265 response to pain GO:0048484 enteric nervous system development GO:0050770 regulation of axonogenesis GO:0051897 positive regulation of protein kinase B signaling GO:0060041 retina development in camera-type eye GO:0060384 innervation GO:0061146 Peyer's patch morphogenesis GO:0071300 cellular response to retinoic acid GO:0072300 positive regulation of metanephric glomerulus development GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand GO:0033139 regulation of peptidyl-serine phosphorylation of STAT protein