RET_RAT
ID RET_RAT Reviewed; 1115 AA.
AC G3V9H8; Q9EPA1; Q9EPC3;
DT 22-JAN-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase receptor Ret;
DE EC=2.7.10.1;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11328649; DOI=10.3109/10425170009033991;
RA Matera I., De Miguel-Rodriguez M., Fernandez-Santos J.M., Santamaria G.,
RA Puliti A., Ravazzolo R., Romeo G., Galera-Davidson H., Ceccherini I.;
RT "cDNA sequence and genomic structure of the rat RET proto-oncogene.";
RL DNA Seq. 11:405-417(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH CBLC AND CD2AP, 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 [5]
RP INTERACTION WITH GFRA1.
RX PubMed=23333276; DOI=10.1016/j.celrep.2012.12.011;
RA Glerup S., Lume M., Olsen D., Nyengaard J.R., Vaegter C.B., Gustafsen C.,
RA Christensen E.I., Kjolby M., Hay-Schmidt A., Bender D., Madsen P.,
RA Saarma M., Nykjaer A., Petersen C.M.;
RT "SorLA controls neurotrophic activity by sorting of GDNF and its receptors
RT GFRalpha1 and RET.";
RL Cell Rep. 3:186-199(2013).
RN [6]
RP TISSUE SPECIFICITY.
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).
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 (By similarity). Mediates, through
CC interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in
CC the brainstem which induces inhibition of food-intake. Activates
CC MAPK- and AKT-signaling pathways (By similarity).
CC {ECO:0000250|UniProtKB:P07949, ECO:0000250|UniProtKB:P35546}.
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 -!- SUBUNIT: Phosphorylated form interacts with the PBT domain of DOK2,
CC DOK4 and DOK5 (By similarity). The phosphorylated form interacts with
CC PLCG1 and GRB7 (By similarity). 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 (By similarity). 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. Interaction with GFRAL requires previous GDF15-
CC binding to GFRAL (By similarity). Interacts with GFRA1; in the presence
CC of SORL1, the GFRA1/RET complex is targeted to endosomes
CC (PubMed:23333276). Interacts with GFRA1; in the presence of SORL1, the
CC GFRA1/RET complex is targeted to endosomes (PubMed:23333276). Interacts
CC with GDNF (By similarity). {ECO:0000250|UniProtKB:P07949,
CC ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:18753381,
CC ECO:0000269|PubMed:23333276}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P07949};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P07949}.
CC Endosome membrane {ECO:0000250|UniProtKB:P07949}; Single-pass type I
CC membrane protein {ECO:0000250|UniProtKB:P07949}. Note=Predominantly
CC located on the plasma membrane. In the presence of SORL1 and GFRA1,
CC directed to endosomes. {ECO:0000250|UniProtKB:P07949}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Ret51;
CC IsoId=G3V9H8-1; Sequence=Displayed;
CC Name=2; Synonyms=Ret9;
CC IsoId=G3V9H8-2; Sequence=VSP_053545, VSP_053546, VSP_053547;
CC -!- TISSUE SPECIFICITY: Expressed in neurons and kidney glomeruli podocytes
CC (at protein level) (PubMed:18753381). Detected at least in colon,
CC duodenum, adipose tissue, heart, jejenum, lung, muscle, spleen, stomac,
CC testis and thymus (PubMed:28846099). {ECO:0000269|PubMed:18753381,
CC ECO:0000269|PubMed:28846099}.
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 -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AJ299016; CAC10568.1; -; mRNA.
DR EMBL; AJ299017; CAC10569.1; -; mRNA.
DR EMBL; AJ298999; CAC10584.1; -; Genomic_DNA.
DR EMBL; AJ299000; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299001; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299002; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299003; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299004; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299005; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299006; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299007; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299008; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299009; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299010; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299011; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299012; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299013; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ299014; CAC10584.1; JOINED; Genomic_DNA.
DR EMBL; AJ298999; CAC10583.1; -; Genomic_DNA.
DR EMBL; AJ299000; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299001; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299002; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299003; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299004; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299005; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299006; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299007; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299008; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299009; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299010; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299011; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299012; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299013; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299014; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AJ299015; CAC10583.1; JOINED; Genomic_DNA.
DR EMBL; AABR06033186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473964; EDM02082.1; -; Genomic_DNA.
DR EMBL; CH473964; EDM02083.1; -; Genomic_DNA.
DR RefSeq; NP_036775.2; NM_012643.2. [G3V9H8-1]
DR RefSeq; XP_017447959.1; XM_017592470.1. [G3V9H8-1]
DR AlphaFoldDB; G3V9H8; -.
DR SMR; G3V9H8; -.
DR BioGRID; 246844; 4.
DR STRING; 10116.ENSRNOP00000047793; -.
DR BindingDB; G3V9H8; -.
DR ChEMBL; CHEMBL4295641; -.
DR GlyGen; G3V9H8; 9 sites.
DR iPTMnet; G3V9H8; -.
DR PhosphoSitePlus; G3V9H8; -.
DR PaxDb; G3V9H8; -.
DR PRIDE; G3V9H8; -.
DR DNASU; 24716; -.
DR Ensembl; ENSRNOT00000047685; ENSRNOP00000047793; ENSRNOG00000014751. [G3V9H8-1]
DR GeneID; 24716; -.
DR KEGG; rno:24716; -.
DR CTD; 5979; -.
DR RGD; 3556; Ret.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000158499; -.
DR HOGENOM; CLU_009530_0_0_1; -.
DR InParanoid; G3V9H8; -.
DR OMA; FHLGQHL; -.
DR OrthoDB; 153428at2759; -.
DR PhylomeDB; G3V9H8; -.
DR TreeFam; TF317640; -.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-8853659; RET signaling.
DR PRO; PR:G3V9H8; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Proteomes; UP000234681; Chromosome 4.
DR Bgee; ENSRNOG00000014751; Expressed in cerebellum and 16 other tissues.
DR Genevisible; G3V9H8; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0098797; C:plasma membrane protein complex; ISO:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:RGD.
DR GO; GO:0001838; P:embryonic epithelial tube formation; ISO:RGD.
DR GO; GO:0048484; P:enteric nervous system development; ISO:RGD.
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; IMP:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0033619; P:membrane protein proteolysis; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD.
DR GO; GO:0007158; P:neuron cell-cell adhesion; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0042551; P:neuron maturation; ISO:RGD.
DR GO; GO:0061146; P:Peyer's patch morphogenesis; ISO:RGD.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0014042; P:positive regulation of neuron maturation; IMP:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:RGD.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0050770; P:regulation of axonogenesis; ISO:RGD.
DR GO; GO:0030155; P:regulation of cell adhesion; ISO:RGD.
DR GO; GO:0048265; P:response to pain; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISO:RGD.
DR GO; GO:0035799; P:ureter maturation; ISO:RGD.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
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 Alternative splicing; ATP-binding; Calcium; Cell adhesion; Cell membrane;
KW Disulfide bond; Endosome; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1115
FT /note="Proto-oncogene tyrosine-protein kinase receptor Ret"
FT /id="PRO_0000424874"
FT CHAIN 29..708
FT /note="Extracellular cell-membrane anchored RET cadherin
FT 120 kDa fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424875"
FT CHAIN 709..1018
FT /note="Soluble RET kinase fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424876"
FT TOPO_DOM 24..637
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..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:0000250|UniProtKB:P07949"
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 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 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 469
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 555
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 137..142
FT /evidence="ECO:0000250"
FT VAR_SEQ 922..928
FT /note="ESLFDHI -> NSLSDHF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11328649"
FT /id="VSP_053545"
FT VAR_SEQ 1065..1073
FT /note="MSDPNWPGE -> RISHAFTRF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11328649"
FT /id="VSP_053546"
FT VAR_SEQ 1074..1115
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11328649"
FT /id="VSP_053547"
FT CONFLICT 30
FT /note="Y -> C (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="S -> A (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="Y -> YD (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="K -> R (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="V -> F (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="I -> T (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="G -> A (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 749
FT /note="G -> D (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 917
FT /note="K -> N (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
FT CONFLICT 975
FT /note="D -> N (in Ref. 1; CAC10568/CAC10583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1115 AA; 124237 MW; BF6EE55077F10F35 CRC64;
MAKARSGAAG LGLKLFLLLP LLGEAPLGLY FSRDAYWERL YVDQPAGTPL LYVHALRDAP
GEVPSFRLGQ YLYGVYRTRL HENDWIHIDS GTGLLYLNQS LDHSSWEQLS IRNGGFPLLT
VFLQVFLGST AQREGECHWP GCARVYFSFI NDTFPNCSSF KARDLCTPET GVSFRIRENR
PPGTFYQFRM LPVQFLCPNI SVKYKLLEGD GLPFRCDPDC LEVSTRWALD RELQEKYVLE
AECAVAGPGA NKEKVAVSFP VTVYDEDDSP PTFSGGVGTA SAVVEFKRKE GTVVATLQVF
DADVVPASGE LVRRYTSTLL SGDSWAQQTF RVEHTPNETL VQSNNNSVRA TMHNYKLVLN
RSLSISESRV LQLVVLVNDS DFQGPGSGVL FLHFNVSVLP VTLNLPMAYS FPVNRRARRY
AQIGKVCVEN CQEFSGVSIQ YKLQPSSTNC SALGVVTSTE DTSGTLYVND TEALRRPECT
ELQYTVVATD RQTRRQTQAS LVVTVEGTYI AEEVGCPKSC AVNKRRPECE ECGGLGSPTG
RCEWRQGDGK GITRNFSTCS PSTRTCPDGH CDALESRDIN ICPQDCLRGP IVGGHERGER
QGIKAGYGIC NCFPDEKKCF CEPEDSQGPL CDELCRTVIT AAVLFSFIIS VLLSTFCIHR
YHKHAHKPPI ASAEMTFCRP AQGFPISYSS SGTRRPSLDS MENQVSVDSF KIPEDPKWEF
PRKNLVLGKT LGEGEFGKVV KATAFRLKGR AGYTTVAVKM LKENASQSEL RDLLSEFNLL
KQVNHPHVIK LYGACSQDGP LLLIVEYAKY GSLRGFLRDS RKIGPAYVSS GGSRNSSSLD
HPDERVLTMG DLISFAWQIS RGMQYLAEMK LVHRDLAARN ILVAEGRKMK ISDFGLSRDV
YEEDSYVKKS KGRIPVKWMA IESLFDHIYT TQSDVWSFGV LLWEIVTLGG NPYPGIPPER
LFNLLKTGHR MERPDNCSEE MYRLMLQCWK QEPDKRPVFA DISKDLEKMM VKSRDYLDLA
ASTPSDSLLY DDGLSEEETP LVDCNSAPLP RSLPSTWIEN KLYGMSDPNW PGESPVPLTR
ADGTSTGFPR YANDSVYANW MVSPSAAKLM DTFDS
