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WNT6_HUMAN
ID   WNT6_HUMAN              Reviewed;         365 AA.
AC   Q9Y6F9; Q9H1J6; Q9H238;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   20-JUN-2001, sequence version 2.
DT   03-AUG-2022, entry version 169.
DE   RecName: Full=Protein Wnt-6;
DE   Flags: Precursor;
GN   Name=WNT6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Testa T.T., Mossakowska D.E., Carter P.S., Hu E., Zhu Y., Kelsell D.P.,
RA   Murdock P.R., Herrity N.C., Lewis C.J., Cross D.A., Culbert A.A.,
RA   Reith A.D., Barnes M.R.;
RT   "Molecular cloning and characterization of six novel human WNT genes.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11350055; DOI=10.1006/bbrc.2001.4855;
RA   Kirikoshi H., Sekihara H., Katoh M.;
RT   "WNT10A and WNT6, clustered in human chromosome 2q35 region with head-to-
RT   tail manner, are strongly co-expressed in SW480 cells.";
RL   Biochem. Biophys. Res. Commun. 283:798-805(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-365.
RA   Rump A., Hayes C., Brown S.D.M., Rosenthal A.;
RT   "Genomic sequence of the Wnt6 gene and the Wnt10a gene from human 2q35.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 295-337.
RX   PubMed=10343101; DOI=10.1159/000015212;
RA   Rankin J., Strachan T., Lako M., Lindsay S.;
RT   "Partial cloning and assignment of WNT6 to human chromosome band 2q35 by in
RT   situ hybridization.";
RL   Cytogenet. Cell Genet. 84:50-52(1999).
RN   [7]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=22370641; DOI=10.1038/onc.2012.40;
RA   Yuan G., Regel I., Lian F., Friedrich T., Hitkova I., Hofheinz R.D.,
RA   Stroebel P., Langer R., Keller G., Roecken C., Zimmermann W., Schmid R.M.,
RA   Ebert M.P.A., Burgermeister E.;
RT   "WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to
RT   epirubicin in human gastric cancer cells.";
RL   Oncogene 32:375-387(2013).
CC   -!- FUNCTION: Ligand for members of the frizzled family of seven
CC       transmembrane receptors. Probable developmental protein. May be a
CC       signaling molecule which affects the development of discrete regions of
CC       tissues. Is likely to signal over only few cell diameters. Together
CC       with CAV1 may promote chemoresistance of gastric cancer cells to DNA-
CC       damaging anthracycline drugs through the activation of the canonical
CC       Wnt receptor signaling pathway. {ECO:0000269|PubMed:22370641}.
CC   -!- SUBUNIT: Interacts with PORCN. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix.
CC   -!- TISSUE SPECIFICITY: Expressed in gastric cancer cell lines and gastric
CC       cancer tissues (at protein level). Detected in the apical gland region
CC       of the gastric foveolar epithelium (at protein level).
CC       {ECO:0000269|PubMed:22370641}.
CC   -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC       receptors. Depalmitoleoylation leads to Wnt signaling pathway
CC       inhibition. {ECO:0000250|UniProtKB:P27467,
CC       ECO:0000250|UniProtKB:P56704}.
CC   -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR   EMBL; AY009401; AAG38661.1; -; mRNA.
DR   EMBL; AB059570; BAB55603.1; -; mRNA.
DR   EMBL; BT007456; AAP36124.1; -; mRNA.
DR   EMBL; BC004329; AAH04329.1; -; mRNA.
DR   EMBL; AF315943; AAG45154.1; -; Genomic_DNA.
DR   EMBL; AF079522; AAD41674.1; -; Genomic_DNA.
DR   CCDS; CCDS2425.1; -.
DR   PIR; JC7694; JC7694.
DR   RefSeq; NP_006513.1; NM_006522.3.
DR   AlphaFoldDB; Q9Y6F9; -.
DR   SMR; Q9Y6F9; -.
DR   BioGRID; 113312; 12.
DR   STRING; 9606.ENSP00000233948; -.
DR   GlyGen; Q9Y6F9; 2 sites.
DR   iPTMnet; Q9Y6F9; -.
DR   PhosphoSitePlus; Q9Y6F9; -.
DR   BioMuta; WNT6; -.
DR   DMDM; 14424016; -.
DR   MassIVE; Q9Y6F9; -.
DR   PaxDb; Q9Y6F9; -.
DR   PeptideAtlas; Q9Y6F9; -.
DR   PRIDE; Q9Y6F9; -.
DR   ProteomicsDB; 86672; -.
DR   Antibodypedia; 34291; 249 antibodies from 34 providers.
DR   DNASU; 7475; -.
DR   Ensembl; ENST00000233948.4; ENSP00000233948.3; ENSG00000115596.4.
DR   GeneID; 7475; -.
DR   KEGG; hsa:7475; -.
DR   MANE-Select; ENST00000233948.4; ENSP00000233948.3; NM_006522.4; NP_006513.1.
DR   UCSC; uc002vjc.2; human.
DR   CTD; 7475; -.
DR   DisGeNET; 7475; -.
DR   GeneCards; WNT6; -.
DR   HGNC; HGNC:12785; WNT6.
DR   HPA; ENSG00000115596; Low tissue specificity.
DR   MIM; 604663; gene.
DR   neXtProt; NX_Q9Y6F9; -.
DR   OpenTargets; ENSG00000115596; -.
DR   PharmGKB; PA37386; -.
DR   VEuPathDB; HostDB:ENSG00000115596; -.
DR   eggNOG; KOG3913; Eukaryota.
DR   GeneTree; ENSGT00940000159281; -.
DR   HOGENOM; CLU_033039_1_3_1; -.
DR   InParanoid; Q9Y6F9; -.
DR   OMA; EQTNCKC; -.
DR   OrthoDB; 624528at2759; -.
DR   PhylomeDB; Q9Y6F9; -.
DR   TreeFam; TF105310; -.
DR   PathwayCommons; Q9Y6F9; -.
DR   Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking.
DR   Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR   SignaLink; Q9Y6F9; -.
DR   SIGNOR; Q9Y6F9; -.
DR   BioGRID-ORCS; 7475; 48 hits in 1067 CRISPR screens.
DR   ChiTaRS; WNT6; human.
DR   GenomeRNAi; 7475; -.
DR   Pharos; Q9Y6F9; Tbio.
DR   PRO; PR:Q9Y6F9; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q9Y6F9; protein.
DR   Bgee; ENSG00000115596; Expressed in endometrium epithelium and 99 other tissues.
DR   Genevisible; Q9Y6F9; HS.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; TAS:Reactome.
DR   GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0005109; F:frizzled binding; IBA:GO_Central.
DR   GO; GO:0009798; P:axis specification; IEA:Ensembl.
DR   GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR   GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
DR   GO; GO:0061303; P:cornea development in camera-type eye; ISS:BHF-UCL.
DR   GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl.
DR   GO; GO:0072079; P:nephron tubule formation; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:BHF-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR   GO; GO:0070172; P:positive regulation of tooth mineralization; IMP:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR   Gene3D; 3.30.2460.20; -; 1.
DR   InterPro; IPR005817; Wnt.
DR   InterPro; IPR009143; Wnt6.
DR   InterPro; IPR043158; Wnt_C.
DR   InterPro; IPR018161; Wnt_CS.
DR   PANTHER; PTHR12027; PTHR12027; 1.
DR   Pfam; PF00110; wnt; 1.
DR   PRINTS; PR01845; WNT6PROTEIN.
DR   PRINTS; PR01349; WNTPROTEIN.
DR   SMART; SM00097; WNT1; 1.
DR   PROSITE; PS00246; WNT1; 1.
PE   1: Evidence at protein level;
KW   Developmental protein; Disulfide bond; Extracellular matrix; Glycoprotein;
KW   Lipoprotein; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..365
FT                   /note="Protein Wnt-6"
FT                   /id="PRO_0000041440"
FT   REGION          140..164
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        142..159
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   LIPID           228
FT                   /note="O-palmitoleoyl serine; by PORCN"
FT                   /evidence="ECO:0000250|UniProtKB:P56704"
FT   CARBOHYD        86
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        311
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        76..87
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        124..132
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        134..172
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        222..236
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        224..231
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        294..325
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        310..320
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        324..364
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        340..355
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        342..352
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        347..348
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
SQ   SEQUENCE   365 AA;  39721 MW;  928DE396C58E295B CRC64;
     MLPPLPSRLG LLLLLLLCPA HVGGLWWAVG SPLVMDPTSI CRKARRLAGR QAELCQAEPE
     VVAELARGAR LGVRECQFQF RFRRWNCSSH SKAFGRILQQ DIRETAFVFA ITAAGASHAV
     TQACSMGELL QCGCQAPRGR APPRPSGLPG TPGPPGPAGS PEGSAAWEWG GCGDDVDFGD
     EKSRLFMDAR HKRGRGDIRA LVQLHNNEAG RLAVRSHTRT ECKCHGLSGS CALRTCWQKL
     PPFREVGARL LERFHGASRV MGTNDGKALL PAVRTLKPPG RADLLYAADS PDFCAPNRRT
     GSPGTRGRAC NSSAPDLSGC DLLCCGRGHR QESVQLEENC LCRFHWCCVV QCHRCRVRKE
     LSLCL
 
 
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