RET_MOUSE
ID RET_MOUSE Reviewed; 1115 AA.
AC P35546; Q8BQ34; Q9QXH9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase receptor Ret;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Ret;
DE Contains:
DE RecName: Full=Soluble RET kinase fragment;
DE Contains:
DE RecName: Full=Extracellular cell-membrane anchored RET cadherin 120 kDa fragment;
DE Flags: Precursor;
GN Name=Ret;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8455936;
RA Iwamoto T., Taniguchi M., Asai N., Ohkusu K., Nakashima I., Takahashi M.;
RT "cDNA cloning of mouse ret proto-oncogene and its sequence similarity to
RT the cadherin superfamily.";
RL Oncogene 8:1087-1091(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Phua C.Y.D., Too H.P.;
RT "Molecular characterization of mouse neuro-2a c-ret proto-oncogene.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ;
RA Wang Y.-Z., Yoong L.-F., Too H.-P.;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH GRB7 AND PLCG1.
RX PubMed=8631863; DOI=10.1074/jbc.271.18.10607;
RA Pandey A., Liu X., Dixon J.E., Di Fiore P.P., Dixit V.M.;
RT "Direct association between the Ret receptor tyrosine kinase and the Src
RT homology 2-containing adapter protein Grb7.";
RL J. Biol. Chem. 271:10607-10610(1996).
RN [7]
RP INTERACTION WITH DOK2; DOK4 AND DOK5, PHOSPHORYLATION, AND MUTAGENESIS OF
RP TYR-1063.
RX PubMed=11470823; DOI=10.1083/jcb.200102032;
RA Grimm J., Sachs M., Britsch S., Di Cesare S., Schwarz-Romond T.,
RA Alitalo K., Birchmeier W.;
RT "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret
RT receptor tyrosine kinase and mediate neuronal differentiation.";
RL J. Cell Biol. 154:345-354(2001).
RN [8]
RP FUNCTION IN PEYER'S PATCH ORGANOGENESIS, AND INTERACTION WITH ARTN.
RX PubMed=17322904; DOI=10.1038/nature05597;
RA Veiga-Fernandes H., Coles M.C., Foster K.E., Patel A., Williams A.,
RA Natarajan D., Barlow A., Pachnis V., Kioussis D.;
RT "Tyrosine kinase receptor RET is a key regulator of Peyer's patch
RT organogenesis.";
RL Nature 446:547-551(2007).
RN [9]
RP INTERACTION WITH CD2AP AND CBLC, AND TISSUE SPECIFICITY.
RX PubMed=18753381; DOI=10.1523/jneurosci.2738-08.2008;
RA Tsui C.C., Pierchala B.A.;
RT "CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation
RT of ret signal transduction.";
RL J. Neurosci. 28:8789-8800(2008).
RN [10]
RP FUNCTION IN NOCICEPTORS REGULATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20237269; DOI=10.1523/jneurosci.5930-09.2010;
RA Golden J.P., Hoshi M., Nassar M.A., Enomoto H., Wood J.N., Milbrandt J.,
RA Gereau R.W. IV, Johnson E.M. Jr., Jain S.;
RT "RET signaling is required for survival and normal function of
RT nonpeptidergic nociceptors.";
RL J. Neurosci. 30:3983-3994(2010).
RN [11]
RP ACTIVITY REGULATION.
RX PubMed=21134556; DOI=10.1016/j.surg.2010.09.026;
RA Samadi A.K., Mukerji R., Shah A., Timmermann B.N., Cohen M.S.;
RT "A novel RET inhibitor with potent efficacy against medullary thyroid
RT cancer in vivo.";
RL Surgery 148:1228-1236(2010).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=28953886; DOI=10.1038/nature24042;
RA Hsu J.Y., Crawley S., Chen M., Ayupova D.A., Lindhout D.A., Higbee J.,
RA Kutach A., Joo W., Gao Z., Fu D., To C., Mondal K., Li B., Kekatpure A.,
RA Wang M., Laird T., Horner G., Chan J., McEntee M., Lopez M.,
RA Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., Matern H.,
RA Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., Alice Chen Y.,
RA Tian H., Allan B.B.;
RT "Non-homeostatic body weight regulation through a brainstem-restricted
RT receptor for GDF15.";
RL Nature 550:255-259(2017).
RN [13]
RP ERRATUM OF PUBMED:28953886.
RX PubMed=29144449; DOI=10.1038/nature24481;
RA Hsu J.Y., Crawley S., Chen M., Ayupova D.A., Lindhout D.A., Higbee J.,
RA Kutach A., Joo W., Gao Z., Fu D., To C., Mondal K., Li B., Kekatpure A.,
RA Wang M., Laird T., Horner G., Chan J., McEntee M., Lopez M.,
RA Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., Matern H.,
RA Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., Alice Chen Y.,
RA Tian H., Allan B.B.;
RT "Non-homeostatic body weight regulation through a brainstem-restricted
RT receptor for GDF15.";
RL Nature 551:398-398(2017).
RN [14]
RP FUNCTION, AND INTERACTION WITH GFRAL.
RX PubMed=28846099; DOI=10.1038/nm.4394;
RA Yang L., Chang C.C., Sun Z., Madsen D., Zhu H., Padkjaer S.B., Wu X.,
RA Huang T., Hultman K., Paulsen S.J., Wang J., Bugge A., Frantzen J.B.,
RA Noergaard P., Jeppesen J.F., Yang Z., Secher A., Chen H., Li X., John L.M.,
RA Shan B., He Z., Gao X., Su J., Hansen K.T., Yang W., Joergensen S.B.;
RT "GFRAL is the receptor for GDF15 and is required for the anti-obesity
RT effects of the ligand.";
RL Nat. Med. 23:1158-1166(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1055-1067, AND PHOSPHORYLATION AT
RP TYR-1063.
RX PubMed=14607833; DOI=10.1074/jbc.m311030200;
RA Shi N., Ye S., Bartlam M., Yang M., Wu J., Liu Y., Sun F., Han X., Peng X.,
RA Qiang B., Yuan J., Rao Z.;
RT "Structural basis for the specific recognition of RET by the Dok1
RT phosphotyrosine binding domain.";
RL J. Biol. Chem. 279:4962-4969(2004).
CC -!- FUNCTION: Receptor tyrosine-protein kinase involved in numerous
CC cellular mechanisms including cell proliferation, neuronal navigation,
CC cell migration, and cell differentiation upon binding with glial cell
CC derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1.
CC Regulates both cell death/survival balance and positional information.
CC Required for the molecular mechanisms orchestration during intestine
CC organogenesis; involved in the development of enteric nervous system
CC and renal organogenesis during embryonic life, and promotes the
CC formation of Peyer's patch-like structures, a major component of the
CC gut-associated lymphoid tissue. Modulates cell adhesion via its
CC cleavage by caspase in sympathetic neurons and mediates cell migration
CC in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the
CC development of the neural crest. Active in the absence of ligand,
CC triggering apoptosis through a mechanism that requires receptor
CC intracellular caspase cleavage. Acts as a dependence receptor; in the
CC presence of the ligand GDNF in somatotrophs (within pituitary),
CC promotes survival and down regulates growth hormone (GH) production,
CC but triggers apoptosis in absence of GDNF. Regulates nociceptor
CC survival and size. Triggers the differentiation of rapidly adapting
CC (RA) mechanoreceptors. Mediator of several diseases such as
CC neuroendocrine cancers; these diseases are characterized by aberrant
CC integrins-regulated cell migration. Mediates, through interaction with
CC GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem
CC which induces inhibition of food-intake. Activates MAPK- and AKT-
CC signaling pathways (PubMed:28846099). {ECO:0000269|PubMed:17322904,
CC ECO:0000269|PubMed:20237269, ECO:0000269|PubMed:28846099}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Repressed by withaferin A (WA).
CC {ECO:0000269|PubMed:21134556}.
CC -!- SUBUNIT: Phosphorylated form interacts with the PBT domain of DOK2,
CC DOK4 and DOK5 (PubMed:11470823). The phosphorylated form interacts with
CC PLCG1 and GRB7 (PubMed:8631863). Interacts (not phosphorylated) with
CC PTK2/FAK1 (via FERM domain) (By similarity). Extracellular cell-
CC membrane anchored RET cadherin fragments form complex in neurons with
CC reduced trophic status, preferentially at the contact sites between
CC somas (By similarity). Interacts with AIP in the pituitary gland; this
CC interaction prevents the formation of the AIP-survivin complex (By
CC similarity). Binds to ARTN (PubMed:17322904). Interacts (inactive) with
CC CBLC and CD2AP; dissociates upon activation by GDNF which increases
CC CBLC:CD2AP interaction (PubMed:18753381). Interacts (via the
CC extracellular domain) with GFRAL (via the extracellular domain); the
CC interaction mediates cellular signaling upon interaction of GFRAL with
CC its ligand GDF15 (PubMed:28846099). Interaction with GFRAL requires
CC previous GDF15-binding to GFRAL (PubMed:28846099). Interacts with
CC GFRA1; in the presence of SORL1, the GFRA1/RET complex is targeted to
CC endosomes. Interacts with GDNF (By similarity).
CC {ECO:0000250|UniProtKB:P07949, ECO:0000269|PubMed:11470823,
CC ECO:0000269|PubMed:17322904, ECO:0000269|PubMed:18753381,
CC ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:8631863}.
CC -!- INTERACTION:
CC P35546-2; Q60629: Epha5; NbExp=5; IntAct=EBI-5548911, EBI-1267609;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P07949};
CC Single-pass type I membrane protein. Endosome membrane
CC {ECO:0000250|UniProtKB:P07949}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:P07949}. Note=Predominantly located on the
CC plasma membrane. In the presence of SORL1 and GFRA1, directed to
CC endosomes. {ECO:0000250|UniProtKB:P07949}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ret51;
CC IsoId=P35546-1; Sequence=Displayed;
CC Name=2; Synonyms=Ret9;
CC IsoId=P35546-2; Sequence=VSP_011304;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral nerve cells, hematopoietic
CC cells and podocytes (PubMed:18753381). Expressed in the brainstem,
CC restricted to cells in the area postrema and the immediately adjacent
CC region of the nucleus tractus solitarius (PubMed:28953886).
CC {ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:28953886}.
CC -!- PTM: Autophosphorylated on C-terminal tyrosine residues upon ligand
CC stimulation. Dephosphorylated by PTPRJ on Tyr-906, Tyr-1016 and Tyr-
CC 1063 (By similarity). {ECO:0000250|UniProtKB:P07949}.
CC -!- PTM: Proteolytically cleaved by caspase-3. The soluble RET kinase
CC fragment is able to induce cell death. The extracellular cell-membrane
CC anchored RET cadherin fragment accelerates cell adhesion in sympathetic
CC neurons (By similarity). {ECO:0000250|UniProtKB:P07949}.
CC -!- DISRUPTION PHENOTYPE: Exclusive loss in nociceptors results in a
CC reduction in nociceptor number and size with a reduced epidermal
CC innervation, but increased sensitivity to cold and increased formalin-
CC induced pain. {ECO:0000269|PubMed:20237269}.
CC -!- MISCELLANEOUS: Treatment with withaferin A (WA) leads tumor regression
CC in medullary thyroid carcinomas (MTC).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; X67812; CAA48013.1; -; mRNA.
DR EMBL; AF209436; AAF21033.1; -; mRNA.
DR EMBL; AY326397; AAP88379.1; -; mRNA.
DR EMBL; AK051633; BAC34699.1; -; mRNA.
DR EMBL; BC059012; AAH59012.1; -; mRNA.
DR CCDS; CCDS20470.1; -. [P35546-1]
DR CCDS; CCDS39608.1; -. [P35546-2]
DR PIR; I48735; S29926.
DR RefSeq; NP_001074249.1; NM_001080780.1. [P35546-2]
DR RefSeq; NP_033076.2; NM_009050.2. [P35546-1]
DR PDB; 1UEF; X-ray; 2.50 A; C/D=1055-1067.
DR PDBsum; 1UEF; -.
DR AlphaFoldDB; P35546; -.
DR SMR; P35546; -.
DR BioGRID; 202865; 23.
DR CORUM; P35546; -.
DR ELM; P35546; -.
DR IntAct; P35546; 12.
DR MINT; P35546; -.
DR STRING; 10090.ENSMUSP00000032201; -.
DR BindingDB; P35546; -.
DR ChEMBL; CHEMBL2034799; -.
DR GlyGen; P35546; 12 sites.
DR iPTMnet; P35546; -.
DR PhosphoSitePlus; P35546; -.
DR EPD; P35546; -.
DR MaxQB; P35546; -.
DR PaxDb; P35546; -.
DR PRIDE; P35546; -.
DR ProteomicsDB; 253117; -. [P35546-1]
DR ProteomicsDB; 253118; -. [P35546-2]
DR Antibodypedia; 1904; 1246 antibodies from 41 providers.
DR DNASU; 19713; -.
DR Ensembl; ENSMUST00000032201; ENSMUSP00000032201; ENSMUSG00000030110. [P35546-1]
DR Ensembl; ENSMUST00000088790; ENSMUSP00000086169; ENSMUSG00000030110. [P35546-2]
DR GeneID; 19713; -.
DR KEGG; mmu:19713; -.
DR UCSC; uc009dlm.1; mouse. [P35546-1]
DR UCSC; uc009dln.1; mouse. [P35546-2]
DR CTD; 5979; -.
DR MGI; MGI:97902; Ret.
DR VEuPathDB; HostDB:ENSMUSG00000030110; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000158499; -.
DR HOGENOM; CLU_009530_0_0_1; -.
DR InParanoid; P35546; -.
DR OMA; FHLGQHL; -.
DR OrthoDB; 153428at2759; -.
DR PhylomeDB; P35546; -.
DR TreeFam; TF317640; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 19713; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Ret; mouse.
DR EvolutionaryTrace; P35546; -.
DR PRO; PR:P35546; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P35546; protein.
DR Bgee; ENSMUSG00000030110; Expressed in ventral tegmental area and 206 other tissues.
DR Genevisible; P35546; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0098797; C:plasma membrane protein complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI.
DR GO; GO:0001838; P:embryonic epithelial tube formation; IGI:MGI.
DR GO; GO:0048484; P:enteric nervous system development; IMP:MGI.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0060384; P:innervation; ISO:MGI.
DR GO; GO:0000165; P:MAPK cascade; IGI:MGI.
DR GO; GO:0033619; P:membrane protein proteolysis; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0001755; P:neural crest cell migration; IMP:MGI.
DR GO; GO:0007158; P:neuron cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0042551; P:neuron maturation; IMP:MGI.
DR GO; GO:0061146; P:Peyer's patch morphogenesis; IMP:UniProtKB.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:MGI.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0072300; P:positive regulation of metanephric glomerulus development; IMP:UniProtKB.
DR GO; GO:0014042; P:positive regulation of neuron maturation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IMP:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; ISO:MGI.
DR GO; GO:0048265; P:response to pain; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IGI:MGI.
DR GO; GO:0035799; P:ureter maturation; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR IDEAL; IID50274; -.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR041163; Ret_CLD1.
DR InterPro; IPR040667; Ret_CLD3.
DR InterPro; IPR041317; RET_CLD4.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016249; Tyr_kinase_Ret_rcpt.
DR Pfam; PF00028; Cadherin; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17756; RET_CLD1; 1.
DR Pfam; PF17812; RET_CLD3; 1.
DR Pfam; PF17813; RET_CLD4; 1.
DR PIRSF; PIRSF000631; TyrPK_receptor_Ret; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49313; SSF49313; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50268; CADHERIN_2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell adhesion;
KW Cell membrane; Disulfide bond; Endosome; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..1115
FT /note="Proto-oncogene tyrosine-protein kinase receptor Ret"
FT /id="PRO_0000024451"
FT CHAIN 29..708
FT /note="Extracellular cell-membrane anchored RET cadherin
FT 120 kDa fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000415294"
FT CHAIN 709..1018
FT /note="Soluble RET kinase fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000415295"
FT TOPO_DOM 29..637
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..659
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 660..1115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 168..273
FT /note="Cadherin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 725..1017
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 875
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 731..739
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 759
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 708..709
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT SITE 1018..1019
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 807
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 810
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 901
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 906
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 982
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 1016
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 1063
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14607833"
FT MOD_RES 1091
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT MOD_RES 1097
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P07949"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 450
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 556
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 137..142
FT /evidence="ECO:0000250"
FT VAR_SEQ 1065..1115
FT /note="MSDPNWPGESPVPLTRADGTSTGFPRYANDSVYANWMVSPSAAKLMDTFDS
FT -> RISHAFTRF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|Ref.3"
FT /id="VSP_011304"
FT MUTAGEN 1063
FT /note="Y->F: Abolishes interaction with DOK proteins."
FT /evidence="ECO:0000269|PubMed:11470823"
FT CONFLICT 174
FT /note="F -> S (in Ref. 1; CAA48013)"
FT /evidence="ECO:0000305"
FT STRAND 1057..1059
FT /evidence="ECO:0007829|PDB:1UEF"
FT TURN 1061..1064
FT /evidence="ECO:0007829|PDB:1UEF"
SQ SEQUENCE 1115 AA; 123874 MW; A5CF1EF45A640413 CRC64;
MAKATSGAAG LGLKLILLLP LLGEAPLGLY FSRDAYWERL YVDQPAGTPL LYVHALRDAP
GEVPSFRLGQ HLYGVYRTRL HENDWIRINE TTGLLYLNQS LDHSSWEQLS IRNGGFPLLT
IFLQVFLGST AQREGECHWP GCTRVYFSFI NDTFPNCSSF KAQDLCIPET AVSFRVRENR
PPGTFYHFHM LPVQFLCPNI SVKYSLLGGD SLPFRCDPDC LEVSTRWALD RELREKYVLE
ALCIVAGPGA NKETVTLSFP VTVYDEDDSA PTFSGGVGTA SAVVEFKRKE GTVVATLQVF
DADVVPASGE LVRRYTNTLL SGDSWAQQTF RVEHSPIETL VQVNNNSVRA TMHNYKLILN
RSLSISESRV LQLAVLVNDS DFQGPGAGGI LVLHFNVSVL PVTLNLPRAY SFPVNKRARR
YAQIGKVCVE NCQEFSGVSI QYKLQPSSIN CTALGVVTSP EDTSGTLFVN DTEALRRPEC
TKLQYTVVAT DRQTRRQTQA SLVVTVEGTS ITEEVGCPKS CAVNKRRPEC EECGGLGSPT
GRCEWRQGDG KGITRNFSTC SPSTRTCPDG HCDAVESRDA NICPQDCLRA DIVGGHERGE
RQGIKAGYGI CNCFPDEKKC FCEPEDSQGP LCDALCRTII TAALFSLIIS ILLSIFCVCH
HHKHGHKPPI ASAEMTFCRP AQGFPISYSS SGTRRPSLDS TENQVPVDSF KIPEDPKWEF
PRKNLVLGKT LGEGEFGKVV KATAFRLKGR AGYTTVAVKM LKENASQSEL RDLLSEFNLL
KQVNHPHVIK LYGACSQDGP LLLIVEYAKY GSLRGFLRDS RKIGPAYVSG GGSRNSSSLD
HPDERVLTMG DLISFAWQIS RGMQYLAEMK LVHRDLAARN ILVAEGRKMK ISDFGLSRDV
YEEDSYVKKS KGRIPVKWMA IESLFDHIYT TQSDVWSFGV LLWEIVTLGG NPYPGIPPER
LFNLLKTGHR MERPDNCSEE MYRLMLQCWK QEPDKRPVFA DISKDLEKMM VKSRDYLDLA
ASTPSDSLLY DDGLSEEETP LVDCNNAPLP RSLPSTWIEN KLYGMSDPNW PGESPVPLTR
ADGTSTGFPR YANDSVYANW MVSPSAAKLM DTFDS
