Tclin RET Proto-oncogene tyrosine-protein kinase receptor Ret

Protein Summary

Description

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. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846097, PubMed:28953886, PubMed:28846099). Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL (PubMed:28846099). This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]

Uniprot Accession IDs

• P07949
• A8K6Z2
• Q15250
• Q9BTB0
• Q9H4A2

Gene Name

• RET

Ensembl ID

• ENST00000340058
• ENSP00000344798
• ENSG00000165731
• ENST00000355710
• ENSP00000347942

Symbol

• CDHF12
• CDHR16
• PTC
• RET51
• PTC
• MTC1
• HSCR1
• MEN2A
• MEN2B
• CDHF12
• CDHR16
• RET-ELE1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
biological process	0.99
hub protein	0.99
molecular function	0.99
protein domain	0.99

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Ret Family / Proto-oncogene Tyrosine-protein Kinase Receptor Ret

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4517.14   (req: < 5)

Gene RIFs: 721   (req: <= 3)

Antibodies: 1078   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4517.14   (req: >= 5)

Gene RIFs: 721   (req: > 3)

Antibodies: 1078   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 48

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 274

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 15