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 14-DEC-2022, entry version 201. 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. {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 ProteomicsDB; 253117; -. [P35546-1] DR ProteomicsDB; 253118; -. [P35546-2] DR Antibodypedia; 1904; 1243 antibodies from 40 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 AGR; MGI:97902; -. 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: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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. 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: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; Cadherin-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 //