lmmol · Proteins

Proto-oncogene tyrosine-protein kinase receptor Ret

UniProt P07949 Organism Homo sapiens Gene CDHF12, CDHR16, PTC, RET EC 2.7.10.1

Also known as: CDHF12, CDHR16, PTC, RET

Function

Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation. GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways. Acts as a dependence receptor via the GDNF-GFRA1 signaling: 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. Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: 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 (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses. 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. Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1.

Classification

Family (Pfam)
PF00028 Cadherin, PF07714 PK_Tyr_Ser-Thr, PF17756 RET_CLD1, PF17812 RET_CLD3, PF17813 RET_CLD4, PF22540 RET_CRD
InterPro
Cadherin-like_dom, Cadherin-like_sf, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ret_CLD1, Ret_CLD3, RET_CLD4, RET_CRD, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_Ret_rcpt
Functional cluster
Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 34

A predicted model is available from AlphaFold.

Gene Ontology · 32

Disease associations

Drugs targeting this protein · 14

Neighborhood · nearest proteins

CDHF12RetRetEphb4CCDC6AIPGOLGA5
Nearest neighbours of Proto-oncogene tyrosine-protein kinase receptor Ret: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 108 cited papers

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