ID WNT3A_HUMAN Reviewed; 352 AA. AC P56704; Q3SY79; Q3SY80; Q969P2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2002, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Protein Wnt-3a; DE Flags: Precursor; GN Name=WNT3A; 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] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=11414706; DOI=10.1006/bbrc.2001.5105; RA Saitoh T., Hirai M., Katoh M.; RT "Molecular cloning and characterization of WNT3a and WNT14 clustered in RT human chromosome 1q42 region."; RL Biochem. Biophys. Res. Commun. 284:1168-1175(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [MRNA] OF 207-330. RC TISSUE=Mammary gland; RX PubMed=8168088; RA Huguet E.L., McMahon J.A., McMahon A.P., Bicknell R., Harris A.L.; RT "Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast RT cell lines and normal and disease states of human breast tissue."; RL Cancer Res. 54:2615-2621(1994). RN [6] RP INTERACTION WITH GPC3. RX PubMed=16227623; DOI=10.1074/jbc.m507004200; RA Capurro M.I., Shi W., Sandal S., Filmus J.; RT "Processing by convertases is not required for glypican-3-induced RT stimulation of hepatocellular carcinoma growth."; RL J. Biol. Chem. 280:41201-41206(2005). RN [7] RP INTERACTION WITH WLS. RX PubMed=16678095; DOI=10.1016/j.cell.2006.02.049; RA Baenziger C., Soldini D., Schuett C., Zipperlen P., Hausmann G., Basler K.; RT "Wntless, a conserved membrane protein dedicated to the secretion of Wnt RT proteins from signaling cells."; RL Cell 125:509-522(2006). RN [8] RP INTERACTION WITH LRP6 IN THE WNT/FZD/LRP6 COMPLEX, AND FUNCTION. RX PubMed=20093360; DOI=10.1074/jbc.m109.092130; RA Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., Costa M., RA Cochran A.G., Hannoush R.N.; RT "Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals RT multiple Wnt and Dkk1 binding sites on LRP6."; RL J. Biol. Chem. 285:9172-9179(2010). RN [9] RP PALMITOLEOYLATION AT SER-209 BY PORCN, AND MUTAGENESIS OF SER-209. RX PubMed=20826466; DOI=10.1242/jcs.072132; RA Coombs G.S., Yu J., Canning C.A., Veltri C.A., Covey T.M., Cheong J.K., RA Utomo V., Banerjee N., Zhang Z.H., Jadulco R.C., Concepcion G.P., RA Bugni T.S., Harper M.K., Mihalek I., Jones C.M., Ireland C.M., RA Virshup D.M.; RT "WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar RT acidification."; RL J. Cell Sci. 123:3357-3367(2010). RN [10] RP INTERACTION WITH APCDD1. RX PubMed=20393562; DOI=10.1038/nature08875; RA Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A., RA Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A., RA Christiano A.M.; RT "APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis RT simplex."; RL Nature 464:1043-1047(2010). RN [11] RP FUNCTION, PRELIMINARY CYSTEINE PALMITOYLATION, PALMITOLEOYLATION AT RP SER-209, GLYCOSYLATION AT ASN-87 AND ASN-298, AND MUTAGENESIS OF ASN-87; RP SER-209 AND ASN-298. RX PubMed=21244856; DOI=10.1016/j.cellsig.2011.01.007; RA Doubravska L., Krausova M., Gradl D., Vojtechova M., Tumova L., Lukas J., RA Valenta T., Pospichalova V., Fafilek B., Plachy J., Sebesta O., Korinek V.; RT "Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for RT lipidation at cysteine and is essential for Wnt signalling."; RL Cell. Signal. 23:837-848(2011). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BONDS, AND MUTAGENESIS OF RP SER-209; CYS-334 AND CYS-335. RX PubMed=24841207; DOI=10.1074/jbc.m114.575027; RA MacDonald B.T., Hien A., Zhang X., Iranloye O., Virshup D.M., RA Waterman M.L., He X.; RT "Disulfide bond requirements for active wnt ligands."; RL J. Biol. Chem. 289:18122-18136(2014). RN [13] RP LACK OF PALMITOYLATION AT CYS-77, AND PALMITOLEOYLATION AT SER-209 BY RP PORCN. RX PubMed=24292069; DOI=10.1038/nchembio.1392; RA Gao X., Hannoush R.N.; RT "Single-cell imaging of Wnt palmitoylation by the acyltransferase RT porcupine."; RL Nat. Chem. Biol. 10:61-68(2014). RN [14] RP PALMITOLEOYLATION AT SER-209, AND DEPALMITOLEOYLATION. RX PubMed=25731175; DOI=10.1038/nature14259; RA Kakugawa S., Langton P.F., Zebisch M., Howell S.A., Chang T.H., Liu Y., RA Feizi T., Bineva G., O'Reilly N., Snijders A.P., Jones E.Y., Vincent J.P.; RT "Notum deacylates Wnt proteins to suppress signalling activity."; RL Nature 519:187-192(2015). RN [15] RP INTERACTION WITH AFM, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26902720; DOI=10.7554/elife.11621; RA Mihara E., Hirai H., Yamamoto H., Tamura-Kawakami K., Matano M., RA Kikuchi A., Sato T., Takagi J.; RT "Active and water-soluble form of lipidated Wnt protein is maintained by a RT serum glycoprotein afamin/alpha-albumin."; RL Elife 5:0-0(2016). RN [16] RP INTERACTION WITH PKD1. RX PubMed=27214281; DOI=10.1038/ncb3363; RA Kim S., Nie H., Nesin V., Tran U., Outeda P., Bai C.X., Keeling J., RA Maskey D., Watnick T., Wessely O., Tsiokas L.; RT "The polycystin complex mediates Wnt/Ca(2+) signalling."; RL Nat. Cell Biol. 18:752-764(2016). CC -!- FUNCTION: Ligand for members of the frizzled family of seven CC transmembrane receptors (Probable). Functions in the canonical Wnt CC signaling pathway that results in activation of transcription factors CC of the TCF/LEF family (PubMed:20093360, PubMed:21244856, CC PubMed:24841207, PubMed:26902720). Required for normal embryonic CC mesoderm development and formation of caudal somites. Required for CC normal morphogenesis of the developing neural tube (By similarity). CC Mediates self-renewal of the stem cells at the bottom on intestinal CC crypts (in vitro) (PubMed:26902720). {ECO:0000250|UniProtKB:P27467, CC ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:21244856, CC ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720, ECO:0000305}. CC -!- SUBUNIT: Forms a soluble 1:1 complex with AFM; this prevents CC oligomerization and is required for prolonged biological activity CC (PubMed:26902720). The complex with AFM may represent the physiological CC form in body fluids (PubMed:26902720). Homooligomer; disulfide-linked, CC leading to inactivation (By similarity). Interacts with PORCN CC (PubMed:20826466). Interacts with APCDD1 and WLS (PubMed:16678095, CC PubMed:20393562). Component of the Wnt-Fzd-LRP5-LRP6 signaling complex CC that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts CC directly in the complex with LRP6 (PubMed:20093360). Interacts with CC glypican GPC3 (PubMed:16227623). Interacts with PKD1 (via extracellular CC domain) (PubMed:27214281). {ECO:0000250|UniProtKB:P27467, CC ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:16678095, CC ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:20393562, CC ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720, CC ECO:0000269|PubMed:27214281, ECO:0000305|PubMed:20826466}. CC -!- INTERACTION: CC P56704; Q8J025: APCDD1; NbExp=3; IntAct=EBI-6173037, EBI-2683489; CC P56704; Q9H461: FZD8; NbExp=2; IntAct=EBI-6173037, EBI-6254212; CC P56704; O75581: LRP6; NbExp=2; IntAct=EBI-6173037, EBI-910915; CC P56704; Q5T9L3: WLS; NbExp=4; IntAct=EBI-6173037, EBI-2868748; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250|UniProtKB:P27467}. Secreted CC {ECO:0000269|PubMed:24841207, ECO:0000269|PubMed:26902720}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P56704-1; Sequence=Displayed; CC Name=2; CC IsoId=P56704-2; Sequence=VSP_046558; CC -!- TISSUE SPECIFICITY: Moderately expressed in placenta and at low levels CC in adult lung, spleen, and prostate. {ECO:0000269|PubMed:11414706}. CC -!- PTM: Palmitoleoylation by PORCN is required for efficient binding to CC frizzled receptors. Palmitoleoylation is required for proper CC trafficking to cell surface, vacuolar acidification is critical to CC release palmitoleoylated WNT3A from WLS in secretory vesicles CC (PubMed:20826466, PubMed:21244856, PubMed:24292069). Depalmitoleoylated CC by NOTUM, leading to inhibit Wnt signaling pathway, possibly by CC promoting disulfide bond formation and oligomerization CC (PubMed:25731175). {ECO:0000269|PubMed:20826466, CC ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24292069, CC ECO:0000269|PubMed:25731175}. CC -!- PTM: Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and CC formation of large disulfide-bond oligomers, leading to inactivation of CC WNT3A. {ECO:0000250|UniProtKB:P27467}. CC -!- PTM: Disulfide bonds have critical and distinct roles in secretion and CC activity. Loss of each conserved cysteine in WNT3A results in high CC molecular weight oxidized Wnt oligomers, which are formed through CC inter-Wnt disulfide bonding. {ECO:0000269|PubMed:24841207}. CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}. CC -!- CAUTION: A palmitoylation site was proposed at Cys-77, but it was later CC shown that this cysteine is engaged in a disulfide bond CC (PubMed:24292069). {ECO:0000269|PubMed:24292069}. 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; AB060284; BAB61052.1; -; mRNA. DR EMBL; AK056278; BAB71136.1; -; mRNA. DR EMBL; AL136379; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC103921; AAI03922.1; -; mRNA. DR EMBL; BC103922; AAI03923.1; -; mRNA. DR EMBL; BC103923; AAI03924.1; -; mRNA. DR CCDS; CCDS1564.1; -. [P56704-1] DR RefSeq; NP_149122.1; NM_033131.3. [P56704-1] DR PDB; 7DRT; EM; 2.20 A; A=1-352. DR PDB; 7URD; EM; 2.92 A; B=199-220. DR PDB; 7URE; EM; 3.19 A; B=199-220. DR PDB; 8TZR; EM; 3.50 A; A=1-352. DR PDBsum; 7DRT; -. DR PDBsum; 7URD; -. DR PDBsum; 7URE; -. DR PDBsum; 8TZR; -. DR AlphaFoldDB; P56704; -. DR EMDB; EMD-26709; -. DR EMDB; EMD-26710; -. DR EMDB; EMD-30827; -. DR EMDB; EMD-41767; -. DR SMR; P56704; -. DR BioGRID; 124599; 40. DR DIP; DIP-58592N; -. DR IntAct; P56704; 20. DR STRING; 9606.ENSP00000284523; -. DR BindingDB; P56704; -. DR ChEMBL; CHEMBL1255137; -. DR GlyCosmos; P56704; 2 sites, No reported glycans. DR GlyGen; P56704; 2 sites. DR iPTMnet; P56704; -. DR PhosphoSitePlus; P56704; -. DR BioMuta; WNT3A; -. DR DMDM; 20532424; -. DR MassIVE; P56704; -. DR PaxDb; 9606-ENSP00000284523; -. DR PeptideAtlas; P56704; -. DR ProteomicsDB; 56937; -. [P56704-1] DR Antibodypedia; 34658; 662 antibodies from 36 providers. DR DNASU; 89780; -. DR Ensembl; ENST00000284523.2; ENSP00000284523.1; ENSG00000154342.6. [P56704-1] DR GeneID; 89780; -. DR KEGG; hsa:89780; -. DR MANE-Select; ENST00000284523.2; ENSP00000284523.1; NM_033131.4; NP_149122.1. DR UCSC; uc001hrq.3; human. [P56704-1] DR AGR; HGNC:15983; -. DR CTD; 89780; -. DR DisGeNET; 89780; -. DR GeneCards; WNT3A; -. DR HGNC; HGNC:15983; WNT3A. DR HPA; ENSG00000154342; Tissue enriched (placenta). DR MalaCards; WNT3A; -. DR MIM; 606359; gene. DR neXtProt; NX_P56704; -. DR OpenTargets; ENSG00000154342; -. DR Orphanet; 85193; Idiopathic juvenile osteoporosis. DR PharmGKB; PA38074; -. DR VEuPathDB; HostDB:ENSG00000154342; -. DR eggNOG; KOG3913; Eukaryota. DR GeneTree; ENSGT00940000160510; -. DR HOGENOM; CLU_033039_1_0_1; -. DR InParanoid; P56704; -. DR OMA; GLTHVMA; -. DR OrthoDB; 2874082at2759; -. DR PhylomeDB; P56704; -. DR TreeFam; TF105310; -. DR PathwayCommons; P56704; -. DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT. DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists. DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination. DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants. DR Reactome; R-HSA-9793380; Formation of paraxial mesoderm. DR Reactome; R-HSA-9832991; Formation of the posterior neural plate. DR SignaLink; P56704; -. DR SIGNOR; P56704; -. DR BioGRID-ORCS; 89780; 15 hits in 1159 CRISPR screens. DR ChiTaRS; WNT3A; human. DR GeneWiki; WNT3A; -. DR GenomeRNAi; 89780; -. DR Pharos; P56704; Tchem. DR PRO; PR:P56704; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P56704; Protein. DR Bgee; ENSG00000154342; Expressed in placenta and 24 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome. 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:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0039706; F:co-receptor binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0005109; F:frizzled binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0048018; F:receptor ligand activity; IDA:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl. DR GO; GO:0090245; P:axis elongation involved in somitogenesis; IEA:Ensembl. DR GO; GO:0007411; P:axon guidance; IEA:Ensembl. DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl. DR GO; GO:0090676; P:calcium ion transmembrane transport via low voltage-gated calcium channel; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0060923; P:cardiac muscle cell fate commitment; IDA:BHF-UCL. DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0021846; P:cell proliferation in forebrain; ISS:BHF-UCL. DR GO; GO:0033278; P:cell proliferation in midbrain; TAS:ParkinsonsUK-UCL. DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB. DR GO; GO:0010387; P:COP9 signalosome assembly; ISS:BHF-UCL. DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IDA:BHF-UCL. DR GO; GO:0001947; P:heart looping; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0030879; P:mammary gland development; IEA:Ensembl. DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0045445; P:myoblast differentiation; IEA:Ensembl. DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IEA:Ensembl. DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:0050768; P:negative regulation of neurogenesis; ISS:BHF-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:0048343; P:paraxial mesodermal cell fate commitment; IEA:Ensembl. DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:2000081; P:positive regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation; IEA:Ensembl. DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IEA:Ensembl. DR GO; GO:0048697; P:positive regulation of collateral sprouting in absence of injury; IEA:Ensembl. DR GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl. DR GO; GO:0061184; P:positive regulation of dermatome development; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IEA:Ensembl. DR GO; GO:0048337; P:positive regulation of mesodermal cell fate specification; IDA:BHF-UCL. DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IEA:Ensembl. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:BHF-UCL. DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl. DR GO; GO:0099054; P:presynapse assembly; TAS:ParkinsonsUK-UCL. DR GO; GO:0008104; P:protein localization; IEA:Ensembl. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IEA:Ensembl. DR GO; GO:1905539; P:regulation of postsynapse to nucleus signaling pathway; IEA:Ensembl. DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO. DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO. DR GO; GO:0062009; P:secondary palate development; IMP:BHF-UCL. DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl. DR GO; GO:0048103; P:somatic stem cell division; IEA:Ensembl. DR GO; GO:0021527; P:spinal cord association neuron differentiation; IEA:Ensembl. DR GO; GO:0036465; P:synaptic vesicle recycling; TAS:ParkinsonsUK-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0021874; P:Wnt signaling pathway involved in forebrain neuroblast division; IEA:Ensembl. DR CDD; cd19335; Wnt_Wnt3_Wnt3a; 1. DR Gene3D; 3.30.2460.20; -; 1. DR InterPro; IPR005817; Wnt. DR InterPro; IPR009141; Wnt3. DR InterPro; IPR043158; Wnt_C. DR InterPro; IPR018161; Wnt_CS. DR PANTHER; PTHR12027:SF88; PROTEIN WNT-3A; 1. DR PANTHER; PTHR12027; WNT RELATED; 1. DR Pfam; PF00110; wnt; 1. DR PRINTS; PR01843; WNT3PROTEIN. DR PRINTS; PR01349; WNTPROTEIN. DR SMART; SM00097; WNT1; 1. DR PROSITE; PS00246; WNT1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Developmental protein; Disulfide bond; KW Extracellular matrix; Glycoprotein; Lipoprotein; Reference proteome; KW Secreted; Signal; Wnt signaling pathway. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..352 FT /note="Protein Wnt-3a" FT /id="PRO_0000041418" FT SITE 26..27 FT /note="Cleavage; by TIKI1 and TIKI2" FT /evidence="ECO:0000250|UniProtKB:P27467" FT LIPID 209 FT /note="O-palmitoleoyl serine; by PORCN" FT /evidence="ECO:0000269|PubMed:20826466, FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24292069, FT ECO:0000269|PubMed:25731175" FT CARBOHYD 87 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21244856" FT CARBOHYD 298 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21244856" FT DISULFID 77..88 FT /evidence="ECO:0000269|PubMed:24292069" FT DISULFID 128..136 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 138..155 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 203..217 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 205..212 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 281..312 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 297..307 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 311..351 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 327..342 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 329..339 FT /evidence="ECO:0000250|UniProtKB:P28026" FT DISULFID 334..335 FT /evidence="ECO:0000250|UniProtKB:P28026" FT VAR_SEQ 352 FT /note="K -> KNPGSRAGNSAHQPPHPQPPVRFHPPLRRAGKVP (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_046558" FT MUTAGEN 87 FT /note="N->Q: Strongly reduced ability to stimulate FT Wnt-responsive reporters; when associated with Q-298." FT /evidence="ECO:0000269|PubMed:21244856" FT MUTAGEN 209 FT /note="S->A: Abrogates WLS binding." FT /evidence="ECO:0000269|PubMed:20826466, FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207" FT MUTAGEN 209 FT /note="S->A: Complete loss of palmitoleoylation." FT /evidence="ECO:0000269|PubMed:20826466, FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207" FT MUTAGEN 209 FT /note="S->T: No effect on palmitoleoylation and secretion; FT the threonine can functionally replace the serine." FT /evidence="ECO:0000269|PubMed:20826466, FT ECO:0000269|PubMed:21244856, ECO:0000269|PubMed:24841207" FT MUTAGEN 298 FT /note="N->Q: Strongly reduced ability to stimulate FT Wnt-responsive reporters; when associated with Q-87." FT /evidence="ECO:0000269|PubMed:21244856" FT MUTAGEN 334 FT /note="C->A: No signaling activity despite the presence of FT significant amounts of secreted monomeric Wnt3a, exhibits FT dominant negative properties; when associated with A-335." FT /evidence="ECO:0000269|PubMed:24841207" FT MUTAGEN 335 FT /note="C->A: No signaling activity despite the presence of FT significant amounts of secreted monomeric Wnt3a, exhibits FT dominant negative properties; when associated with A-334." FT /evidence="ECO:0000269|PubMed:24841207" FT HELIX 23..27 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 35..38 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 50..58 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 63..80 FT /evidence="ECO:0007829|PDB:7DRT" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 100..103 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 107..129 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 134..137 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 145..148 FT /evidence="ECO:0007829|PDB:7DRT" FT TURN 150..153 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 161..169 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 176..178 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 179..197 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 200..207 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 210..220 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 224..237 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 239..246 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 248..251 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 253..258 FT /evidence="ECO:0007829|PDB:7DRT" FT TURN 260..262 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:7DRT" FT TURN 285..288 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 300..304 FT /evidence="ECO:0007829|PDB:7DRT" FT HELIX 307..310 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 319..328 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:7DRT" FT STRAND 340..348 FT /evidence="ECO:0007829|PDB:7DRT" SQ SEQUENCE 352 AA; 39365 MW; A317BD6D4A73920B CRC64; MAPLGYFLLL CSLKQALGSY PIWWSLAVGP QYSSLGSQPI LCASIPGLVP KQLRFCRNYV EIMPSVAEGI KIGIQECQHQ FRGRRWNCTT VHDSLAIFGP VLDKATRESA FVHAIASAGV AFAVTRSCAE GTAAICGCSS RHQGSPGKGW KWGGCSEDIE FGGMVSREFA DARENRPDAR SAMNRHNNEA GRQAIASHMH LKCKCHGLSG SCEVKTCWWS QPDFRAIGDF LKDKYDSASE MVVEKHRESR GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS SHGIDGCDLL CCGRGHNARA ERRREKCRCV FHWCCYVSCQ ECTRVYDVHT CK //