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 12-SEP-2018, entry version 176. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; 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., RA Takahashi M.; RT "cDNA cloning of mouse ret proto-oncogene and its sequence similarity RT to 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA 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 RT project: 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 RT Src 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 RP OF 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 RT c-Ret 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 RT regulation 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., RA Milbrandt J., 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., RA Kekatpure A., Wang M., Laird T., Horner G., Chan J., McEntee M., RA Lopez M., Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., RA Matern H., Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., RA Alice Chen Y., 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. 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., RA Kekatpure A., Wang M., Laird T., Horner G., Chan J., McEntee M., RA Lopez M., Lakshminarasimhan D., White A., Wang S.P., Yao J., Yie J., RA Matern H., Solloway M., Haldankar R., Parsons T., Tang J., Shen W.D., RA Alice Chen Y., 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., RA John L.M., Shan B., He Z., Gao X., Su J., Hansen K.T., Yang W., RA 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 RP PHOSPHORYLATION AT 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., RA Peng X., 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 CC navigation, cell migration, and cell differentiation upon binding CC with glial cell derived neurotrophic factor family ligands. CC Phosphorylates PTK2/FAK1. Regulates both cell death/survival CC balance and positional information. Required for the molecular CC mechanisms orchestration during intestine organogenesis; involved CC in the development of enteric nervous system and renal CC organogenesis during embryonic life, and promotes the formation of CC Peyer's patch-like structures, a major component of the gut- CC associated lymphoid tissue. Modulates cell adhesion via its CC cleavage by caspase in sympathetic neurons and mediates cell CC migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. CC Involved in the development of the neural crest. Active in the CC absence of ligand, triggering apoptosis through a mechanism that CC requires receptor intracellular caspase cleavage. Acts as a CC dependence receptor; in the presence of the ligand GDNF in CC somatotrophs (within pituitary), promotes survival and down CC regulates growth hormone (GH) production, but triggers apoptosis CC in absence of GDNF. Regulates nociceptor survival and size. CC Triggers the differentiation of rapidly adapting (RA) CC mechanoreceptors. Mediator of several diseases such as CC neuroendocrine cancers; these diseases are characterized by CC aberrant integrins-regulated cell migration. Mediates, through CC interaction with GDF15-receptor GFRAL, GDF15-induced cell- CC signaling in the brainstem which induces inhibition of food- CC intake. Activates MAPK- and AKT-signaling pathways CC (PubMed:28846099). {ECO:0000269|PubMed:17322904, CC ECO:0000269|PubMed:20237269, ECO:0000269|PubMed:28846099}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC 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 CC DOK2, DOK4 and DOK5 (PubMed:11470823). The phosphorylated form CC interacts with PLCG1 and GRB7 (PubMed:8631863). Interacts (not CC phosphorylated) with PTK2/FAK1 (via FERM domain) (By similarity). CC Extracellular cell-membrane anchored RET cadherin fragments form CC complex in neurons with reduced trophic status, preferentially at CC the contact sites between somas (By similarity). Interacts with CC AIP in the pituitary gland; this interaction prevents the CC formation of the AIP-survivin complex (By similarity). Binds to CC ARTN (PubMed:17322904). Interacts (inactive) with CBLC and CD2AP; CC dissociates upon activation by GDNF which increases CBLC:CD2AP CC interaction (PubMed:18753381). Interacts (via the extracellular CC domain) with GFRAL (via the extracellular domain); the interaction CC mediates cellular signaling upon interaction of GFRAL with its CC ligand GDF15 (PubMed:28846099). Interaction with GFRAL requires CC previous GDF15-binding to GFRAL (PubMed:28846099). 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 Q60629:Epha5; NbExp=5; IntAct=EBI-5548911, EBI-1267609; CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:P07949}; Single-pass type I membrane CC protein. Endosome membrane {ECO:0000250|UniProtKB:P07949}; Single- CC pass type I membrane protein {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, CC hematopoietic cells and podocytes (PubMed:18753381). Expressed in CC the brainstem, restricted to cells in the area postrema and the CC immediately adjacent region of the nucleus tractus solitarius CC (PubMed:28953886). {ECO:0000269|PubMed:18753381, CC ECO:0000269|PubMed:28953886}. CC -!- PTM: Autophosphorylated on C-terminal tyrosine residues upon CC ligand stimulation. Dephosphorylated by PTPRJ on Tyr-906, Tyr-1016 CC and Tyr-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- CC membrane anchored RET cadherin fragment accelerates cell adhesion CC in sympathetic neurons (By similarity). CC {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 CC formalin-induced pain. {ECO:0000269|PubMed:20237269}. CC -!- MISCELLANEOUS: Treatment with withaferin A (WA) leads tumor CC regression 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 UniGene; Mm.57199; -. DR PDB; 1UEF; X-ray; 2.50 A; C/D=1055-1067. DR PDBsum; 1UEF; -. DR ProteinModelPortal; P35546; -. DR SMR; P35546; -. DR BioGrid; 202865; 3. DR CORUM; P35546; -. DR ELM; P35546; -. DR IntAct; P35546; 10. DR MINT; P35546; -. DR STRING; 10090.ENSMUSP00000032201; -. DR BindingDB; P35546; -. DR ChEMBL; CHEMBL2034799; -. DR iPTMnet; P35546; -. DR PhosphoSitePlus; P35546; -. DR EPD; P35546; -. DR MaxQB; P35546; -. DR PaxDb; P35546; -. DR PRIDE; P35546; -. 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 eggNOG; KOG0200; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00760000118923; -. DR HOGENOM; HOG000010301; -. DR HOVERGEN; HBG002609; -. DR InParanoid; P35546; -. DR KO; K05126; -. DR OMA; WRQGDGK; -. DR OrthoDB; EOG091G0CQZ; -. 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 EvolutionaryTrace; P35546; -. DR PRO; PR:P35546; -. DR Proteomes; UP000000589; Chromosome 6. DR Bgee; ENSMUSG00000030110; Expressed in 244 organ(s), highest expression level in ventral tegmental area. DR CleanEx; MM_RET; -. DR Genevisible; P35546; MM. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0005829; C:cytosol; 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:0043231; C:intracellular membrane-bounded organelle; 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:0000187; P:activation of MAPK activity; ISS:UniProtKB. 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; IDA: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:0043410; P:positive regulation of MAPK cascade; ISO:MGI. 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; IDA: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:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0048265; P:response to pain; IMP:UniProtKB. 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 InterPro; IPR002126; Cadherin. DR InterPro; IPR015919; Cadherin-like. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. 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; Pkinase_Tyr; 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; Complete proteome; Disulfide bond; Endosome; KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Proto-oncogene; Reference proteome; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase. FT SIGNAL 1 28 {ECO:0000255}. FT CHAIN 29 1115 Proto-oncogene tyrosine-protein kinase FT receptor Ret. FT /FTId=PRO_0000024451. FT CHAIN 29 708 Extracellular cell-membrane anchored RET FT cadherin 120 kDa fragment. {ECO:0000250}. FT /FTId=PRO_0000415294. FT CHAIN 709 1018 Soluble RET kinase fragment. FT {ECO:0000250}. FT /FTId=PRO_0000415295. FT TOPO_DOM 29 637 Extracellular. {ECO:0000255}. FT TRANSMEM 638 659 Helical. {ECO:0000255}. FT TOPO_DOM 660 1115 Cytoplasmic. {ECO:0000255}. FT DOMAIN 168 273 Cadherin. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 725 1017 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 731 739 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 806 808 Inhibitors binding. {ECO:0000250}. FT ACT_SITE 875 875 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 759 759 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT BINDING 893 893 Inhibitor. {ECO:0000250}. FT SITE 708 709 Cleavage; by caspase-3. {ECO:0000250}. FT SITE 1018 1019 Cleavage; by caspase-3. {ECO:0000250}. FT MOD_RES 697 697 Phosphoserine. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 807 807 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 810 810 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 901 901 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 906 906 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 982 982 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 1016 1016 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 1063 1063 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:14607833}. FT MOD_RES 1091 1091 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT MOD_RES 1097 1097 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P07949}. FT CARBOHYD 89 89 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 98 98 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 151 151 N-linked (GlcNAc...) asparagine. FT {ECO:0000250}. FT CARBOHYD 156 156 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 199 199 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 345 345 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 360 360 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 378 378 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 396 396 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 450 450 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 470 470 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 556 556 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 137 142 {ECO:0000250}. FT VAR_SEQ 1065 1115 MSDPNWPGESPVPLTRADGTSTGFPRYANDSVYANWMVSPS FT AAKLMDTFDS -> RISHAFTRF (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16141072, FT ECO:0000303|Ref.3}. FT /FTId=VSP_011304. FT MUTAGEN 1063 1063 Y->F: Abolishes interaction with DOK FT proteins. {ECO:0000269|PubMed:11470823}. FT CONFLICT 174 174 F -> S (in Ref. 1; CAA48013). FT {ECO:0000305}. FT STRAND 1057 1059 {ECO:0000244|PDB:1UEF}. FT TURN 1061 1064 {ECO:0000244|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 //