Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

RET (P07949) - Overview - Molecular Target Synopsis


RET, Proto-oncogene tyrosine-protein kinase receptor Ret
Enzyme Classification
UniProt P07949

Also Known as RET_HUMAN, RET, CDHF12, CDHR16, PTC, RET51

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). Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 (By similarity). The phosphorylated form interacts with PLCG1 and GRB7 (By similarity). Interacts (not phosphorylated) with PTK2/FAK1 (via FERM domain) (PubMed:21454698). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas (PubMed:21357690). Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex (PubMed:19366855). Binds to ARTN (By similarity). Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction (PubMed:18753381). Interacts (via the extracellular domain) with GFRAL (via the extracellular domain); the interaction mediates cellular signaling upon interaction of GFRAL with its ligand GDF15 (PubMed:28953886, PubMed:28846097, PubMed:28846099). Interaction with GFRAL requires previous GDF15-binding to GFRAL (PubMed:28846097, PubMed:28846099).

Inspect Structure
See all 3D Structures for RET

Isoforms / Transcripts (Protein Coding)


RET is targeted by Approved Drugs Alectinib Hydrochloride, Sorafenib, Sunitinib, Vandetanib. (see details)
Alectinib Hydrochloride

Sub-cellular localization

UniProt: RET is active in the following subcellular-locations: cell membrane, endosome membrane.
GO terms: RET is active in the following subcellular-locations: axon, cytosol, dendrite, early endosome, endosome membrane, integral component of plasma membrane, intracellular membrane-bounded organelle, membrane raft, neuronal cell body, plasma membrane, plasma membrane protein complex, receptor complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project RET has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: MCF7, HL_60, SR

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK-N-FI, CHP-212, MHH-NB-11

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH_RA, SK-N-SH, MCF-7

(see details)

RNA Interference

RET was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB436, HUO3N1. (see details)

3D Structures

For RET there are:
15 structures (18 chains) solved
14 are solved in complex with at least one small molecule ligand
5 are solved with an approved drug

RET is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

RET has been screened with 1392 compounds (4099 bioactivities), 281 compounds have bioactivities that show binding affinity of <= 500nM (500 bioactivities). (see details)