ID F6WV32_HORSE Unreviewed; 1113 AA.
AC F6WV32;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 2.
DT 27-MAR-2024, entry version 83.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase receptor Ret {ECO:0000256|PIRNR:PIRNR000631};
DE EC=2.7.10.1 {ECO:0000256|PIRNR:PIRNR000631};
GN Name=RET {ECO:0000313|Ensembl:ENSECAP00000002849.2,
GN ECO:0000313|VGNC:VGNC:51660};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000002849.2, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000002849.2, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000002849.2,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000002849.2}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000002849.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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.
CC {ECO:0000256|PIRNR:PIRNR000631}.
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:0000256|ARBA:ARBA00001171,
CC ECO:0000256|PIRNR:PIRNR000631};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|PIRNR:PIRNR000631}.
CC Membrane {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane
CC protein {ECO:0000256|ARBA:ARBA00004479}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000256|PIRNR:PIRNR000631}.
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DR AlphaFoldDB; F6WV32; -.
DR SMR; F6WV32; -.
DR STRING; 9796.ENSECAP00000002849; -.
DR GlyCosmos; F6WV32; 1 site, No reported glycans.
DR PaxDb; 9796-ENSECAP00000002849; -.
DR Ensembl; ENSECAT00000004122.4; ENSECAP00000002849.2; ENSECAG00000001064.4.
DR VGNC; VGNC:51660; RET.
DR GeneTree; ENSGT00940000158499; -.
DR HOGENOM; CLU_009530_0_0_1; -.
DR InParanoid; F6WV32; -.
DR OMA; CDVVENQ; -.
DR OrthoDB; 1614410at2759; -.
DR TreeFam; TF317640; -.
DR Proteomes; UP000002281; Chromosome 1.
DR Bgee; ENSECAG00000001064; Expressed in oviduct epithelium and 19 other cell types or tissues.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:Ensembl.
DR GO; GO:0098797; C:plasma membrane protein complex; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005509; F:calcium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0001838; P:embryonic epithelial tube formation; IEA:Ensembl.
DR GO; GO:0048484; P:enteric nervous system development; IEA:Ensembl.
DR GO; GO:0035860; P:glial cell-derived neurotrophic factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0033619; P:membrane protein proteolysis; IEA:Ensembl.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0007158; P:neuron cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0042551; P:neuron maturation; IEA:Ensembl.
DR GO; GO:0061146; P:Peyer's patch morphogenesis; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0072300; P:positive regulation of metanephric glomerulus development; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR GO; GO:0050770; P:regulation of axonogenesis; IEA:Ensembl.
DR GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0035799; P:ureter maturation; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR CDD; cd11304; Cadherin_repeat; 2.
DR CDD; cd05045; PTKc_RET; 1.
DR Gene3D; 2.60.40.60; Cadherins; 2.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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 PANTHER; PTHR24416:SF485; PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
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 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRNR:PIRNR000631};
KW Calcium {ECO:0000256|PROSITE-ProRule:PRU00043};
KW Cell adhesion {ECO:0000256|PIRNR:PIRNR000631};
KW Cell membrane {ECO:0000256|PIRNR:PIRNR000631};
KW Kinase {ECO:0000256|PIRNR:PIRNR000631};
KW Membrane {ECO:0000256|PIRNR:PIRNR000631};
KW Nucleotide-binding {ECO:0000256|PIRNR:PIRNR000631, ECO:0000256|PROSITE-
KW ProRule:PRU10141}; Reference proteome {ECO:0000313|Proteomes:UP000002281};
KW Signal {ECO:0000256|SAM:SignalP};
KW Transferase {ECO:0000256|PIRNR:PIRNR000631};
KW Tyrosine-protein kinase {ECO:0000256|ARBA:ARBA00023137,
KW ECO:0000256|PIRNR:PIRNR000631}.
FT SIGNAL 1..21
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 22..1113
FT /note="Proto-oncogene tyrosine-protein kinase receptor Ret"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5018786852"
FT DOMAIN 166..270
FT /note="Cadherin"
FT /evidence="ECO:0000259|PROSITE:PS50268"
FT DOMAIN 723..1015
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT ACT_SITE 873
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000631-1"
FT BINDING 757
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000256|PIRSR:PIRSR000631-4"
FT DISULFID 135..140
FT /evidence="ECO:0000256|PIRSR:PIRSR000631-3"
SQ SEQUENCE 1113 AA; 124107 MW; E13AF03A0B65EE5D CRC64;
MAKATAGAAG LRLLLLLPLL GEAPLGLYFS RDAYWEKLYV DQPAGTPLLY VHALRDVPEE
VPTFRLGQHL YGAYRTRLHE NDWIRIQEDT GLLYLNQSLD HSSWEQLSVR NGGFPLLTVY
LQVFLSPTSL REGECQWPGC ARVYFSFINT SFPACGSLKP RELCFPETGL SFRVRENRPP
GTFHQFRLLP VQFLCPNVSV AYRLLGGESL PFRCARDSLE VSTRWALDRE RREKYELVAV
CTVRIGAREE EVMVPFLVTV YDEDDSAPTF LGGVDTASAV VEFKRKEGTV VATLRVFDAD
VVPASGELLR RYTSTLLPGD AWALQTFRVE HLPNETLVQA NGSFVRATVH DYRLVLNRSL
PISESRELQL AVLVNDSDFQ GPGEGILLLH FNVSVLPVSL RLPSAYSFTV SRRARRFAQI
GKVCVENCQE FSGIHVQYKL QLPNANCSAL GVVTSAEDTS GTLFVNDTEA LRRPECTQLQ
YTVVAADRPT RRQAQAPVLV TVEGTYMAEE PGCPLSCAVS KRRPECEECG GLGSLTGRCE
WRQGDGKGIT RNFSTCSPSI RTCPDGHCDA VESRDANVCP QDCLRGGSII GGHEPGERRG
IKAGFGICNC FPEEKKCFCE PEDSQALLCD ELCRTVIAAA VLFSFIVSVL LSTFCIHRYH
KNAHKPPIAS AEMTFRRPTQ AFPVSYSSAG ARRPSLDSME NQVSVDAFKI PEDPKWEFPR
KNLVLGKTLG EGEFGKVVEA TAFRLKGKAG YTTVAVKMLK ENASPSELRD LLSEFNLLKQ
VNHPQVIKLY GACSQDGPLL LIVEYAKYGS LRGFLRESRK AGPGYVGSGG SRNSSYLDNP
DERALTMGDL ISFAWQISRG MQYLAEMKLV HRDLAARNVL VAEGRKMKIS DFGLSRDVYE
EDSYVKRSKG RIPVKWMAIE SLFDHIYTTQ SDVWSFGVLL WEIVTLGGNP YPGIPPERLF
NLLKTGYRME RPDNCSEEMY GLMLQCWKQE PDKRPVFADI SKDLEKMMVK SRDYLDLAAS
TPSDSLLYDD GLSEEETPLV DCNNTPLPRT LPSTWIENKL YGMSDPNWPE ESPVPLTRAD
GTNTGCPRYA NDSVYANWMV SPSAAQLMDA FDS
//
