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 04-DEC-2007, entry version 79. DE Proto-oncogene tyrosine-protein kinase receptor ret precursor DE (EC 2.7.10.1) (C-ret). GN Name=Ret; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=93205390; 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). RC STRAIN=A; 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/c; 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/6; 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 DOK2; DOK4 AND DOK5, PHOSPHORYLATION, AND MUTAGENESIS RP OF TYR-1063. RX MEDLINE=21363571; 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). CC -!- FUNCTION: Probable receptor with tyrosine-protein kinase activity; CC important for development. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Phosphorylated form interacts with the PBT domain of CC DOK2, DOK4 and DOK5. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; 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 and CC hematopoietic cells. CC -!- PTM: Phosphorylated. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CC -!- SIMILARITY: Contains 1 cadherin domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. 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 PIR; I48735; S29926. DR RefSeq; NP_033076.2; -. DR UniGene; Mm.57199; -. DR PDB; 1UEF; X-ray; 2.50 A; C/D=1055-1067. DR SMR; P35546; 714-1012. DR Ensembl; ENSMUSG00000030110; Mus musculus. DR GeneID; 19713; -. DR KEGG; mmu:19713; -. DR MGI; MGI:97902; Ret. DR ArrayExpress; P35546; -. DR CleanEx; MM_RET; -. DR GermOnline; ENSMUSG00000030110; Mus musculus. DR GO; GO:0005515; F:protein binding; IPI:MGI. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kin...; TAS: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:0000165; P:MAPKKK cascade; IGI:MGI. DR GO; GO:0001755; P:neural crest cell migration; IMP:MGI. DR GO; GO:0042551; P:neuron maturation; IMP:MGI. DR GO; GO:0001657; P:ureteric bud development; IMP:MGI. DR InterPro; IPR002126; Cadherin. DR InterPro; IPR000719; Prot_kinase_core. DR InterPro; IPR015777; RetRTK. DR InterPro; IPR001245; Tyr_pkinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR Gene3D; G3DSA:2.60.40.60; G3DSA:2.60.40.60; 1. DR PANTHER; PTHR23256:SF245; RetRTK; 2. DR Pfam; PF00028; Cadherin; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PRINTS; PR00109; TYRKINASE. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00112; CA; 1. DR SMART; SM00219; TyrKc; 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; Glycoprotein; Kinase; KW Membrane; Nucleotide-binding; Phosphoprotein; Proto-oncogene; Signal; KW Transferase; Transmembrane; Tyrosine-protein kinase. FT SIGNAL 1 28 Potential. FT CHAIN 29 1115 Proto-oncogene tyrosine-protein kinase FT receptor ret. FT /FTId=PRO_0000024451. FT TOPO_DOM 29 637 Extracellular (Potential). FT TRANSMEM 638 659 Potential. FT TOPO_DOM 660 1115 Cytoplasmic (Potential). FT DOMAIN 168 273 Cadherin. FT DOMAIN 725 1017 Protein kinase. FT NP_BIND 731 739 ATP (By similarity). FT ACT_SITE 875 875 Proton acceptor (By similarity). FT BINDING 759 759 ATP (By similarity). FT MOD_RES 807 807 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 810 810 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 901 901 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 906 906 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 982 982 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 1016 1016 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 1063 1063 Phosphotyrosine; by autocatalysis. FT MOD_RES 1091 1091 Phosphotyrosine; by autocatalysis (By FT similarity). FT MOD_RES 1097 1097 Phosphotyrosine; by autocatalysis (By FT similarity). FT CARBOHYD 89 89 N-linked (GlcNAc...) (Potential). FT CARBOHYD 98 98 N-linked (GlcNAc...) (Potential). FT CARBOHYD 151 151 N-linked (GlcNAc...) (Potential). FT CARBOHYD 156 156 N-linked (GlcNAc...) (Potential). FT CARBOHYD 199 199 N-linked (GlcNAc...) (Potential). FT CARBOHYD 345 345 N-linked (GlcNAc...) (Potential). FT CARBOHYD 360 360 N-linked (GlcNAc...) (Potential). FT CARBOHYD 378 378 N-linked (GlcNAc...) (Potential). FT CARBOHYD 396 396 N-linked (GlcNAc...) (Potential). FT CARBOHYD 450 450 N-linked (GlcNAc...) (Potential). FT CARBOHYD 470 470 N-linked (GlcNAc...) (Potential). FT CARBOHYD 556 556 N-linked (GlcNAc...) (Potential). FT VAR_SEQ 1065 1115 MSDPNWPGESPVPLTRADGTSTGFPRYANDSVYANWMVSPS FT AAKLMDTFDS -> RISHAFTRF (in isoform 2). FT /FTId=VSP_011304. FT MUTAGEN 1063 1063 Y->F: Abolishes interaction with DOK FT proteins. FT CONFLICT 174 174 F -> S (in Ref. 1). FT STRAND 1057 1059 FT TURN 1061 1064 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 //