true1995-02-012024-03-27198WNT5A_HUMANMolecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21.Clark C.C.Cohen I.R.Eichstetter I.Cannizarro L.A.McPherson J.D.Wasmuth J.J.Iozzo R.V.doi:10.1006/geno.1993.14631993Genomics18249-260NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)TISSUE SPECIFICITYComplete sequencing and characterization of 21,243 full-length human cDNAs.Ota T.Suzuki Y.Nishikawa T.Otsuki T.Sugiyama T.Irie R.Wakamatsu A.Hayashi K.Sato H.Nagai K.Kimura K.Makita H.Sekine M.Obayashi M.Nishi T.Shibahara T.Tanaka T.Ishii S.Yamamoto J.Saito K.Kawai Y.Isono Y.Nakamura Y.Nagahari K.Murakami K.Yasuda T.Iwayanagi T.Wagatsuma M.Shiratori A.Sudo H.Hosoiri T.Kaku Y.Kodaira H.Kondo H.Sugawara M.Takahashi M.Kanda K.Yokoi T.Furuya T.Kikkawa E.Omura Y.Abe K.Kamihara K.Katsuta N.Sato K.Tanikawa M.Yamazaki M.Ninomiya K.Ishibashi T.Yamashita H.Murakawa K.Fujimori K.Tanai H.Kimata M.Watanabe M.Hiraoka S.Chiba Y.Ishida S.Ono Y.Takiguchi S.Watanabe S.Yosida M.Hotuta T.Kusano J.Kanehori K.Takahashi-Fujii A.Hara H.Tanase T.-O.Nomura Y.Togiya S.Komai F.Hara R.Takeuchi K.Arita M.Imose N.Musashino K.Yuuki H.Oshima A.Sasaki N.Aotsuka S.Yoshikawa Y.Matsunawa H.Ichihara T.Shiohata N.Sano S.Moriya S.Momiyama H.Satoh N.Takami S.Terashima Y.Suzuki O.Nakagawa S.Senoh A.Mizoguchi H.Goto Y.Shimizu F.Wakebe H.Hishigaki H.Watanabe T.Sugiyama A.Takemoto M.Kawakami B.Yamazaki M.'Watanabe K.Kumagai A.Itakura S.Fukuzumi Y.Fujimori Y.Komiyama M.Tashiro H.Tanigami A.Fujiwara T.Ono T.Yamada K.Fujii Y.Ozaki K.Hirao M.Ohmori Y.Kawabata A.Hikiji T.Kobatake N.Inagaki H.Ikema Y.Okamoto S.Okitani R.Kawakami T.Noguchi S.Itoh T.Shigeta K.Senba T.Matsumura K.Nakajima Y.Mizuno T.Morinaga M.Sasaki M.Togashi T.Oyama M.Hata H.Watanabe M.'Komatsu T.Mizushima-Sugano J.Satoh T.Shirai Y.Takahashi Y.Nakagawa K.Okumura K.Nagase T.Nomura N.Kikuchi H.Masuho Y.Yamashita R.Nakai K.Yada T.Nakamura Y.'Ohara O.Isogai T.Sugano S.doi:10.1038/ng12852004Nat. Genet.3640-45NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)Mesangial cellTongueMural R.J.Istrail S.Sutton G.G.Florea L.Halpern A.L.Mobarry C.M.Lippert R.Walenz B.Shatkay H.Dew I.Miller J.R.Flanigan M.J.Edwards N.J.Bolanos R.Fasulo D.Halldorsson B.V.Hannenhalli S.Turner R.Yooseph S.Lu F.Nusskern D.R.Shue B.C.Zheng X.H.Zhong F.Delcher A.L.Huson D.H.Kravitz S.A.Mouchard L.Reinert K.Remington K.A.Clark A.G.Waterman M.S.Eichler E.E.Adams M.D.Hunkapiller M.W.Myers E.W.Venter J.C.2005-07EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)PlacentaProcessing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements.De Cat B.Muyldermans S.Y.Coomans C.Degeest G.Vanderschueren B.Creemers J.Biemar F.Peers B.David G.doi:10.1083/jcb.2003021522003J. Cell Biol.163625-635INTERACTION WITH GPC3Wnt-5a has tumor suppressor activity in thyroid carcinoma.Kremenevskaja N.von Wasielewski R.Rao A.S.Schoefl C.Andersson T.Brabant G.doi:10.1038/sj.onc.12083702005Oncogene242144-2154FUNCTIONTISSUE SPECIFICITYThe Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition.Dissanayake S.K.Wade M.Johnson C.E.O'Connell M.P.Leotlela P.D.French A.D.Shah K.V.Hewitt K.J.Rosenthal D.T.Indig F.E.Jiang Y.Nickoloff B.J.Taub D.D.Trent J.M.Moon R.T.Bittner M.Weeraratna A.T.doi:10.1074/jbc.m7000752002007J. Biol. Chem.28217259-17271FUNCTIONActive and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin.Mihara E.Hirai H.Yamamoto H.Tamura-Kawakami K.Matano M.Kikuchi A.Sato T.Takagi J.doi:10.7554/elife.116212016Elife5INTERACTION WITH AFMSUBCELLULAR LOCATIONThe polycystin complex mediates Wnt/Ca(2+) signalling.Kim S.Nie H.Nesin V.Tran U.Outeda P.Bai C.X.Keeling J.Maskey D.Watnick T.Wessely O.Tsiokas L.doi:10.1038/ncb33632016Nat. Cell Biol.18752-764INTERACTION WITH PKD1Structure of the human Meckel-Gruber protein Meckelin.Liu D.Qian D.Shen H.Gong D.doi:10.1126/sciadv.abj97482021Sci. Adv.7eabj9748INTERACTION WITH TMEM67WNT5A mutations in patients with autosomal dominant Robinow syndrome.Person A.D.Beiraghi S.Sieben C.M.Hermanson S.Neumann A.N.Robu M.E.Schleiffarth J.R.Billington C.J. Jr.van Bokhoven H.Hoogeboom J.M.Mazzeu J.F.Petryk A.Schimmenti L.A.Brunner H.G.Ekker S.C.Lohr J.L.doi:10.1002/dvdy.221562010Dev. Dyn.239327-337VARIANTS DRS1 SER-83 AND ARG-182CHARACTERIZATION OF VARIANTS DRS1 SER-83 AND ARG-182WNT signaling perturbations underlie the genetic heterogeneity of Robinow syndrome.White J.J.Mazzeu J.F.Coban-Akdemir Z.Bayram Y.Bahrambeigi V.Hoischen A.van Bon B.W.M.Gezdirici A.Gulec E.Y.Ramond F.Touraine R.Thevenon J.Shinawi M.Beaver E.Heeley J.Hoover-Fong J.Durmaz C.D.Karabulut H.G.Marzioglu-Ozdemir E.Cayir A.Duz M.B.Seven M.Price S.Ferreira B.M.Vianna-Morgante A.M.Ellard S.Parrish A.Stals K.Flores-Daboub J.Jhangiani S.N.Gibbs R.A.Brunner H.G.Sutton V.R.Lupski J.R.Carvalho C.M.B.Baylor-Hopkins Center for Mendelian Genomicsdoi:10.1016/j.ajhg.2017.10.0022018Am. J. Hum. Genet.10227-43VARIANTS DRS1 CYS-160 AND GLY-CYS-164 INSAtlas of Genetics and Cytogenetics in Oncology and Haematology68242 N-Linked glycans (1 site)4 sites, 2 glycans4 sites, 2 N-linked glycans (1 site)657 antibodies from 39 providershumanWNT5ATissue enhanced (endometrium, salivary gland)genephenotypeAutosomal dominant Robinow syndromeEukaryotaTCF dependent signaling in response to WNTWNT ligand biogenesis and traffickingClass B/2 (Secretin family receptors)Negative regulation of TCF-dependent signaling by WNT ligand antagonistsCa2+ pathwayPCP/CE pathwayAsymmetric localization of PCP proteinsWNT5A-dependent internalization of FZD4WNT5A-dependent internalization of FZD2, FZD5 and ROR2Cargo recognition for clathrin-mediated endocytosisClathrin-mediated endocytosisWNT5:FZD7-mediated leishmania damping10 hits in 1145 CRISPR screenshumanTbioProteinExpressed in stromal cell of endometrium and 180 other cell types or tissuesbaseline and differentialWnt_Wnt5aWntWnt_CWnt_CSPROTEIN WNT-5AWNT RELATEDwntWNTPROTEINWNT1WNT1HSProtein Wnt-5aWNT5ALigand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor (PubMed:15735754). Mediates motility of melanoma cells (PubMed:17426020). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes (By similarity).Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). Homooligomer; disulfide-linked, leading to inactivation (in vitro). Interacts with PORCN. Interacts with WLS (By similarity). Interacts with glypican GCP3 (PubMed:14610063). Interacts with PKD1 (via extracellular domain) (PubMed:27214281). Interacts with TMEM67 (PubMed:34731008).Expression is increased in differentiated thyroid carcinomas compared to normal thyroid tissue and anaplastic thyroid tumors where expression is low or undetectable. Expression is found in thyrocytes but not in stromal cells (at protein level) (PubMed:15735754). Detected in neonate heart and lung (PubMed:8288227).Glycosylation is necessary for secretion but not for activity.Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT5A.The disease is caused by variants affecting the gene represented in this entry.Belongs to the Wnt family.1353661Protein Wnt-5a3579762380O-palmitoleoyl serine; by PORCN244N-linked (GlcNAc...) asparagine114N-linked (GlcNAc...) asparagine120N-linked (GlcNAc...) asparagine312N-linked (GlcNAc...) asparagine326104115154162164182238252240247309340325335339379355370357367362363In isoform 2.15In DRS1; hypomorphic mutation.S83In DRS1; uncertain significance.C160In DRS1.CGCIn DRS1; hypomorphic mutation.Rfalse2WIF12008-11-042true423392bbaedeb6f985e14559ea40e391483411MKKSIGILSPGVALGMAGSAMSSKFFLVALAIFFSFAQVVIEANSWWSLGMNNPVQMSEVYIIGAQPLCSQLAGLSQGQKKLCHLYQDHMQYIGEGAKTGIKECQYQFRHRRWNCSTVDNTSVFGRVMQIGSRETAFTYAVSAAGVVNAMSRACREGELSTCGCSRAARPKDLPRDWLWGGCGDNIDYGYRFAKEFVDARERERIHAKGSYESARILMNLHNNEAGRRTVYNLADVACKCHGVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMRLNSRGKLVQVNSRFNSPTTQDLVYIDPSPDYCVRNESTGSLGTQGRLCNKTSEGMDGCELMCCGRGYDQFKTVQTERCHCKFHWCCYVKCKKCTEIVDQFVCK2MAGSAMSSKFFLVALAIFFSFAQVVIEANSWWSLGMNNPVQMSEVYIIGAQPLCSQLAGLSQGQKKLCHLYQDHMQYIGEGAKTGIKECQYQFRHRRWNCSTVDNTSVFGRVMQIGSRETAFTYAVSAAGVVNAMSRACREGELSTCGCSRAARPKDLPRDWLWGGCGDNIDYGYRFAKEFVDARERERIHAKGSYESARILMNLHNNEAGRRTVYNLADVACKCHGVSGSCSLKTCWLQLADFRKVGDALKEKYDSAAAMRLNSRGKLVQVNSRFNSPTTQDLVYIDPSPDYCVRNESTGSLGTQGRLCNKTSEGMDGCELMCCGRGYDQFKTVQTERCHCKFHWCCYVKCKKCTEIVDQFVCKtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue