ID WNT3A_HUMAN Reviewed; 352 AA. AC P56704; Q3SY80; Q969P2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2002, sequence version 2. DT 25-JAN-2012, entry version 100. DE RecName: Full=Protein Wnt-3a; DE Flags: Precursor; GN Name=WNT3A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=21308441; 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 RT in human chromosome 1q42 region."; RL Biochem. Biophys. Res. Commun. 284:1168-1175(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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]. 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 207-330. RC TISSUE=Mammary gland; RX MEDLINE=94221588; 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 RT breast cell lines and normal and disease states of human breast RT tissue."; RL Cancer Res. 54:2615-2621(1994). RN [6] 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., RA Basler K.; RT "Wntless, a conserved membrane protein dedicated to the secretion of RT Wnt proteins from signaling cells."; RL Cell 125:509-522(2006). RN [7] RP INTERACTION WITH LRP6 IN THE WNT/FZD/LRP6 COMPLEX. RX PubMed=20093360; DOI=10.1074/jbc.M109.092130; RA Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., RA Costa M., 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 [8] RP PALMITOYLATION 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., RA Cheong J.K., Utomo V., Banerjee N., Zhang Z.H., Jadulco R.C., RA Concepcion G.P., Bugni T.S., Harper M.K., Mihalek I., Jones C.M., RA Ireland C.M., Virshup D.M.; RT "WLS-dependent secretion of WNT3A requires Ser209 acylation and RT vacuolar acidification."; RL J. Cell Sci. 123:3357-3367(2010). RN [9] 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). CC -!- FUNCTION: Ligand for members of the frizzled family of seven CC transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in CC cell-cell signaling during morphogenesis of the developing neural CC tube. CC -!- SUBUNIT: Interacts with PORCN. Interacts with APCDD1 and WLS. CC Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains CC a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly CC in the complex with LRP6. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix. CC -!- TISSUE SPECIFICITY: Moderately expressed in placenta and at low CC levels in adult lung, spleen, and prostate. CC -!- PTM: Palmitoylation at Ser-209 by PORCN is required for proper CC trafficking to cell surface, vacuolar acidification is critical to CC release palmitoylated WNT3A from WLS in secretory vesicles. CC -!- SIMILARITY: Belongs to the Wnt family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB060284; BAB61052.1; -; mRNA. DR EMBL; AK056278; BAB71136.1; -; mRNA. DR EMBL; AL136379; CAI23122.1; -; Genomic_DNA. DR EMBL; BC103922; AAI03923.1; -; mRNA. DR IPI; IPI00654606; -. DR RefSeq; NP_149122.1; NM_033131.3. DR UniGene; Hs.336930; -. DR ProteinModelPortal; P56704; -. DR DIP; DIP-58592N; -. DR STRING; P56704; -. DR DMDM; 20532424; -. DR PRIDE; P56704; -. DR Ensembl; ENST00000284523; ENSP00000284523; ENSG00000154342. DR Ensembl; ENST00000366753; ENSP00000355715; ENSG00000154342. DR GeneID; 89780; -. DR KEGG; hsa:89780; -. DR UCSC; uc001hrq.1; human. DR CTD; 89780; -. DR GeneCards; GC01P228194; -. DR H-InvDB; HIX0001654; -. DR HGNC; HGNC:15983; WNT3A. DR MIM; 606359; gene. DR neXtProt; NX_P56704; -. DR PharmGKB; PA38074; -. DR eggNOG; prNOG13814; -. DR GeneTree; ENSGT00600000084119; -. DR HOVERGEN; HBG001595; -. DR InParanoid; P56704; -. DR OrthoDB; EOG4XD3R9; -. DR PhylomeDB; P56704; -. DR Reactome; REACT_111102; Signal Transduction. DR NextBio; 76263; -. DR ArrayExpress; P56704; -. DR Bgee; P56704; -. DR CleanEx; HS_WNT3A; -. DR Genevestigator; P56704; -. DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL. DR GO; GO:0005769; C:early endosome; IBA:RefGenome. DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL. DR GO; GO:0005770; C:late endosome; IBA:RefGenome. DR GO; GO:0045121; C:membrane raft; IBA:RefGenome. DR GO; GO:0005886; C:plasma membrane; IBA:RefGenome. DR GO; GO:0005578; C:proteinaceous extracellular matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005201; F:extracellular matrix structural constituent; NAS:UniProtKB. DR GO; GO:0005110; F:frizzled-2 binding; IBA:RefGenome. DR GO; GO:0048018; F:receptor agonist activity; IDA:BHF-UCL. DR GO; GO:0003713; F:transcription coactivator activity; ISS:BHF-UCL. DR GO; GO:0009798; P:axis specification; IBA:RefGenome. DR GO; GO:0021846; P:cell proliferation in forebrain; ISS:BHF-UCL. DR GO; GO:0007267; P:cell-cell signaling; NAS:UniProtKB. DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB. DR GO; GO:0060026; P:convergent extension; IBA:RefGenome. DR GO; GO:0061054; P:dermatome development; IDA:BHF-UCL. DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IBA:RefGenome. DR GO; GO:0009880; P:embryonic pattern specification; IBA:RefGenome. DR GO; GO:0030198; P:extracellular matrix organization; IBA:RefGenome. DR GO; GO:0071425; P:hemopoietic stem cell proliferation; IBA:RefGenome. DR GO; GO:0021766; P:hippocampus development; IBA:RefGenome. DR GO; GO:0042472; P:inner ear morphogenesis; IBA:RefGenome. DR GO; GO:0030879; P:mammary gland development; IBA:RefGenome. DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IBA:RefGenome. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IBA:RefGenome. DR GO; GO:0003136; P:negative regulation of heart induction by canonical Wnt receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0030903; P:notochord development; IBA:RefGenome. DR GO; GO:0060021; P:palate development; IMP:BHF-UCL. DR GO; GO:0048343; P:paraxial mesodermal cell fate commitment; IBA:RefGenome. DR GO; GO:0035413; P:positive regulation of catenin import into nucleus; IDA:BHF-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0010387; P:signalosome assembly; ISS:BHF-UCL. DR GO; GO:0035121; P:tail morphogenesis; IBA:RefGenome. DR GO; GO:0021874; P:Wnt receptor signaling pathway involved in forebrain neuroblast division; IBA:RefGenome. DR GO; GO:0007223; P:Wnt receptor signaling pathway, calcium modulating pathway; IBA:RefGenome. DR InterPro; IPR005817; Wnt. DR InterPro; IPR009141; Wnt3. DR InterPro; IPR018161; Wnt_grthfactor_CS. DR KO; K00312; -. DR PANTHER; PTHR12027; Wnt; 1. DR PANTHER; PTHR12027:SF18; Wnt3; 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 Complete proteome; Developmental protein; Extracellular matrix; KW Glycoprotein; Lipoprotein; Palmitate; Reference proteome; Secreted; KW Signal; Wnt signaling pathway. FT SIGNAL 1 18 Potential. FT CHAIN 19 352 Protein Wnt-3a. FT /FTId=PRO_0000041418. FT LIPID 77 77 S-palmitoyl cysteine (By similarity). FT LIPID 209 209 O-palmitoyl serine. FT CARBOHYD 87 87 N-linked (GlcNAc...) (Potential). FT CARBOHYD 298 298 N-linked (GlcNAc...) (Potential). FT MUTAGEN 209 209 S->A: Abrogates WLS binding. 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 //