Ret
entrez
19713
canonical
uniprot
P35546
canonical
ensembl
ENSMUSG00000030110
resolver
ensp
ENSMUSP00000032201
resolver
ensp
ENSMUSP00000086169
resolver
genesymbol
Ret
resolver
uniprot
Q8BQ34
resolver
uniprot
Q9QXH9
resolver
uniprot_entry
RET_MOUSE
resolver
uniprot_sec
Q8BQ34
resolver
uniprot_sec
Q9QXH9
resolver
activity_regulation
ACTIVITY REGULATION: Repressed by withaferin A (WA). {ECO:0000269|PubMed:21134556}.
uniprot
proteins
amino_acid_sequence
MAKATSGAAGLGLKLILLLPLLGEAPLGLYFSRDAYWERLYVDQPAGTPLLYVHALRDAPGEVPSFRLGQHLYGVYRTRLHENDWIRINETTGLLYLNQSLDHSSWEQLSIRNGGFPLLTIFLQVFLGSTAQREGECHWPGCTRVYFSFINDTFPNCSSFKAQDLCIPETAVSFRVRENRPPGTFYHFHMLPVQFLCPNISVKYSLLGGDSLPFRCDPDCLEVSTRWALDRELREKYVLEALCIVAGPGANKETVTLSFPVTVYDEDDSAPTFSGGVGTASAVVEFKRKEGTVVATLQVFDADVVPASGELVRRYTNTLLSGDSWAQQTFRVEHSPIETLVQVNNNSVRATMHNYKLILNRSLSISESRVLQLAVLVNDSDFQGPGAGGILVLHFNVSVLPVTLNLPRAYSFPVNKRARRYAQIGKVCVENCQEFSGVSIQYKLQPSSINCTALGVVTSPEDTSGTLFVNDTEALRRPECTKLQYTVVATDRQTRRQTQASLVVTVEGTSITEEVGCPKSCAVNKRRPECEECGGLGSPTGRCEWRQGDGKGITRNFSTCSPSTRTCPDGHCDAVESRDANICPQDCLRADIVGGHERGERQGIKAGYGICNCFPDEKKCFCEPEDSQGPLCDALCRTIITAALFSLIISILLSIFCVCHHHKHGHKPPIASAEMTFCRPAQGFPISYSSSGTRRPSLDSTENQVPVDSFKIPEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFRLKGRAGYTTVAVKMLKENASQSELRDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRDSRKIGPAYVSGGGSRNSSSLDHPDERVLTMGDLISFAWQISRGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVKKSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKSRDYLDLAASTPSDSLLYDDGLSEEETPLVDCNNAPLPRSLPSTWIENKLYGMSDPNWPGESPVPLTRADGTSTGFPRYANDSVYANWMVSPSAAKLMDTFDS
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
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) (PubMed:17322904, PubMed:20237269, PubMed:28846099). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:17322904, PubMed:20237269, PubMed:28846099). 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 (PubMed:17322904, PubMed:28846099). 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 (PubMed:20237269). 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 (PubMed:17322904). 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 (PubMed:28846099). 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 (By similarity). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (By similarity). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (By similarity). Involved in the development of the neural crest (PubMed:15242795). Regulates nociceptor survival and size (PubMed:20237269). Phosphorylates PTK2/FAK1 (By similarity). {ECO:0000250|UniProtKB:P07949, ECO:0000269|PubMed:15242795, ECO:0000269|PubMed:17322904, ECO:0000269|PubMed:20237269, ECO:0000269|PubMed:28846099}.
uniprot
proteins
mass_dalton
123874
uniprot
proteins
mutagenesis
MUTAGEN 1063; /note="Y->F: Abolishes interaction with DOK proteins."; /evidence="ECO:0000269|PubMed:11470823
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation. {ECO:0000250|UniProtKB:P07949}.; 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). {ECO:0000250|UniProtKB:P07949}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
11470823
uniprot
proteins
pubmed
14607833
uniprot
proteins
pubmed
15242795
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17322904
uniprot
proteins
pubmed
18753381
uniprot
proteins
pubmed
20237269
uniprot
proteins
pubmed
21134556
uniprot
proteins
pubmed
28846099
uniprot
proteins
pubmed
28953886
uniprot
proteins
pubmed
29144449
uniprot
proteins
pubmed
8455936
uniprot
proteins
pubmed
8631863
uniprot
proteins
sequence_length
1115
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P07949}; Single-pass type I membrane protein. Endosome membrane {ECO:0000250|UniProtKB:P07949}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P07949}. Note=Predominantly located on the plasma membrane. In the presence of SORL1 and GFRA1, directed to endosomes. {ECO:0000250|UniProtKB:P07949}.
uniprot
proteins
transmembrane_region
TRANSMEM 638..659; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins