DegronMD - P07949(RET)

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. 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). {ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886}. View more >>

GO - Biological processes (BP): activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; axon guidance [GO:0007411]; cellular response to retinoic acid [GO:0071300]; embryonic epithelial tube formation [GO:0001838]; enteric nervous system development [GO:0048484]; glial cell-derived neurotrophic factor receptor signaling pathway [GO:0035860]; homophilic cell adhesion via plasma membrane adhesion molecules [GO:0007156]; innervation [GO:0060384]; lymphocyte migration into lymphoid organs [GO:0097021]; MAPK cascade [GO:0000165]; membrane protein proteolysis [GO:0033619]; neural crest cell migration [GO:0001755]; neuron cell-cell adhesion [GO:0007158]; neuron maturation [GO:0042551]; Peyer's patch morphogenesis [GO:0061146]; positive regulation of cell adhesion mediated by integrin [GO:0033630]; positive regulation of cell migration [GO:0030335]; positive regulation of cell size [GO:0045793]; positive regulation of extrinsic apoptotic signaling pathway in absence of ligand [GO:2001241]; positive regulation of gene expression [GO:0010628]; positive regulation of kinase activity [GO:0033674]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of metanephric glomerulus development [GO:0072300]; positive regulation of neuron maturation [GO:0014042]; positive regulation of neuron projection development [GO:0010976]; positive regulation of peptidyl-serine phosphorylation of STAT protein [GO:0033141]; positive regulation of protein kinase B signaling [GO:0051897]; positive regulation of transcription, DNA-templated [GO:0045893]; posterior midgut development [GO:0007497]; protein phosphorylation [GO:0006468]; regulation of axonogenesis [GO:0050770]; regulation of cell adhesion [GO:0030155]; response to pain [GO:0048265]; response to xenobiotic stimulus [GO:0009410]; retina development in camera-type eye [GO:0060041]; signal transduction [GO:0007165]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]; ureteric bud development [GO:0001657]; ureter maturation [GO:0035799] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R693C	TCGA-2W-A8YY	CESC	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.719
p.R693C	DO223732	CESC	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.719
p.V757M	TCGA-62-A46Y	LUAD	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.25
p.V757M	DO48883	LUAD	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.25
p.A756G	TCGA-77-8140	LUSC	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.A756G	DO26834	LUSC	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.P766Q	TCGA-95-7039	LUAD	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2778
p.P766Q	DO23907	LUAD	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2778
p.N763K	TCGA-99-8025	LUAD	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation altering degron motif	0.6918
p.N763K	DO24255	LUAD	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation altering degron motif	0.6918
p.A756V	TCGA-AA-A010	COAD	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.V706M	TCGA-AA-A022	COAD	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1944
p.V706M	TCGA-CD-A48C	STAD	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1944
p.V706M	DO10647	COAD	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1944
p.V706M	DO233089	GACA	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1944
p.V706M	DO47912	STAD	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1944
p.E768G	TCGA-E6-A1LX	UCEC	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.E768G	DO41020	UCEC	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.V685I	TCGA-EE-A29D	SKCM	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1111
p.V685I	DO38123	SKCM	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1111
p.V685I	ACH-001651	Endometrial/Uterine Cancer	CCLE	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.1111
p.D698N	TCGA-FW-A3TV	SKCM	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.5821
p.D698N	DO38159	SKCM	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.5821
p.Q703H	TCGA-G5-6641	READ	TCGA	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.2778
p.Q703H	DO36909	READ	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.2778
p.A756D	TCGA-IB-7651	PAAD	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.A756D	DO46657	PAAD	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.2222
p.M759I	TCGA-MA-AA3X	CESC	TCGA	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.3056
p.M759I	DO219720	CESC	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.3056
p.G691S	DO228483	BRCA	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.2778
p.G691S	DO229505	LAML	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.2778
p.G691S	DO231207	LUSC	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation rewiring degron network	0.2778
p.A764T	DO230342	COCA	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation altering degron motif	0.6028
p.A764T	DO52496	COCA	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation altering degron motif	0.6028
p.A764T	DO42673	UCEC	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation altering degron motif	0.6028
p.S686I	DO228974	LICA	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.5833
p.L772P	DO233293	NACA	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.1111
p.T754M	DO228138	PBCA	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation blocking phosphorylation signal	0.6111
p.S705F	DO229446	SKCA	ICGC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6667
p.A750V	DO229264	THCA	ICGC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.0556
p.S765F	SIDM00336	Melanoma	GDSC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.3056
p.S765F	ACH-000881	Skin Cancer	CCLE	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.3056
p.S765F	MEL-JUSO	skin	COSMIC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.3056
p.S688F	SIDM00007	Other Solid Cancers	GDSC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.S688F	ACH-001550	Skin Cancer	CCLE	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.S688F	MCC13	skin	COSMIC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.S688Y	SIDM00598	Squamous Cell Lung Carcinoma	GDSC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.S688Y	ACH-000843	Lung Cancer	CCLE	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.S688Y	HARA	lung	COSMIC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation blocking phosphorylation signal	0.6389
p.A750T	SIDM00151	Ovarian Carcinoma	GDSC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.0556
p.A750T	ACH-000966	Ovarian Cancer	CCLE	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.0556
p.A750T	IGROV-1	ovary	COSMIC	LKENA	DEG_APCC_KENBOX_2	760:764	Mutation rewiring degron network	0.0556
p.P695A	SIDM01045	Endometrial Carcinoma	GDSC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.6392
p.P695A	ACH-000978	Endometrial/Uterine Cancer	CCLE	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.6392
p.P695A	EN	endometrium	COSMIC	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.6392
p.R693H	ACH-000333	Ovarian Cancer	CCLE	RRPSLDSME	DEG_APCC_DBOX_1	693:701	Mutation altering degron motif	0.7133

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

RET

UniProt ID: P07949

Entrez ID: 5979

Protein name: Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RET in