ID   WNT3_HUMAN              Reviewed;         355 AA.
AC   P56703; Q2M237; Q9H1J9;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   20-JUN-2001, sequence version 2.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Proto-oncogene Wnt-3;
DE   AltName: Full=Proto-oncogene Int-4 homolog;
DE   Flags: Precursor;
GN   Name=WNT3; Synonyms=INT4;
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=11604997; DOI=10.3892/ijo.19.5.977;
RA   Katoh M.;
RT   "Molecular cloning and characterization of human WNT3.";
RL   Int. J. Oncol. 19:977-982(2001).
RN   [3]
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-333.
RX   PubMed=8244403; DOI=10.1006/geno.1993.1412;
RA   Roelink H., Wang J., Black D.M., Solomon E., Nusse R.;
RT   "Molecular cloning and chromosomal localization to 17q21 of the human WNT3
RT   gene.";
RL   Genomics 17:790-792(1993).
RN   [5]
RP   INVOLVEMENT IN TETAMS1.
RX   PubMed=14872406; DOI=10.1086/382196;
RA   Niemann S., Zhao C., Pascu F., Stahl U., Aulepp U., Niswander L.,
RA   Weber J.L., Mueller U.;
RT   "Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous
RT   family.";
RL   Am. J. Hum. Genet. 74:558-563(2004).
RN   [6]
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).
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:26902720). Required for normal
CC       gastrulation, formation of the primitive streak, and for the formation
CC       of the mesoderm during early embryogenesis. Required for normal
CC       formation of the apical ectodermal ridge (By similarity). Required for
CC       normal embryonic development, and especially for limb development
CC       (PubMed:14872406). {ECO:0000250|UniProtKB:P17553,
CC       ECO:0000269|PubMed:14872406, 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).Interacts with PORCN. Interacts
CC       with WLS (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P56703; P43652: AFM; NbExp=3; IntAct=EBI-3644922, EBI-20737924;
CC       P56703; O75084: FZD7; NbExp=3; IntAct=EBI-3644922, EBI-746917;
CC       P56703; Q61091: Fzd8; Xeno; NbExp=2; IntAct=EBI-3644922, EBI-6171689;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000305}. Secreted {ECO:0000269|PubMed:26902720}.
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   -!- DISEASE: Tetraamelia syndrome 1 (TETAMS1) [MIM:273395]: A form of
CC       tetraamelia, a rare disease characterized by rudimentary appendages or
CC       complete absence of all four limbs, and other anomalies such as
CC       craniofacial, nervous system, pulmonary, skeletal and urogenital
CC       defects. TETAMS1 patients manifest complete limb agenesis without
CC       defects of scapulae or clavicles. Other features include bilateral
CC       cleft lip/palate, diaphragmatic defect with bilobar right lung, renal
CC       and adrenal agenesis, pelvic hypoplasia, and urogenital defects.
CC       TETAMS1 transmission pattern is consistent with autosomal recessive
CC       inheritance. {ECO:0000269|PubMed:14872406}. Note=The disease is caused
CC       by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR   EMBL; AY009397; AAG38657.1; -; mRNA.
DR   EMBL; AB067628; BAB70502.1; -; mRNA.
DR   EMBL; BC112116; AAI12117.1; -; mRNA.
DR   EMBL; BC112118; AAI12119.1; -; mRNA.
DR   EMBL; BC114219; AAI14220.1; -; mRNA.
DR   CCDS; CCDS11505.1; -.
DR   PIR; A47536; A47536.
DR   RefSeq; NP_110380.1; NM_030753.4.
DR   PDB; 6AHY; X-ray; 2.80 A; B/D/F=42-355.
DR   PDBsum; 6AHY; -.
DR   AlphaFoldDB; P56703; -.
DR   SMR; P56703; -.
DR   BioGRID; 113310; 62.
DR   IntAct; P56703; 5.
DR   STRING; 9606.ENSP00000225512; -.
DR   BindingDB; P56703; -.
DR   ChEMBL; CHEMBL6079; -.
DR   GlyCosmos; P56703; 2 sites, No reported glycans.
DR   GlyGen; P56703; 2 sites.
DR   iPTMnet; P56703; -.
DR   PhosphoSitePlus; P56703; -.
DR   BioMuta; WNT3; -.
DR   DMDM; 14424477; -.
DR   EPD; P56703; -.
DR   MassIVE; P56703; -.
DR   PaxDb; 9606-ENSP00000225512; -.
DR   PeptideAtlas; P56703; -.
DR   ProteomicsDB; 56936; -.
DR   Antibodypedia; 30108; 517 antibodies from 31 providers.
DR   DNASU; 7473; -.
DR   Ensembl; ENST00000225512.6; ENSP00000225512.5; ENSG00000108379.11.
DR   Ensembl; ENST00000611547.1; ENSP00000478327.1; ENSG00000277626.1.
DR   Ensembl; ENST00000616347.2; ENSP00000480990.1; ENSG00000277641.2.
DR   GeneID; 7473; -.
DR   KEGG; hsa:7473; -.
DR   MANE-Select; ENST00000225512.6; ENSP00000225512.5; NM_030753.5; NP_110380.1.
DR   UCSC; uc002ikv.3; human.
DR   AGR; HGNC:12782; -.
DR   CTD; 7473; -.
DR   DisGeNET; 7473; -.
DR   GeneCards; WNT3; -.
DR   HGNC; HGNC:12782; WNT3.
DR   HPA; ENSG00000108379; Group enriched (liver, skin).
DR   MalaCards; WNT3; -.
DR   MIM; 165330; gene.
DR   MIM; 273395; phenotype.
DR   neXtProt; NX_P56703; -.
DR   OpenTargets; ENSG00000108379; -.
DR   Orphanet; 3301; Tetraamelia-multiple malformations syndrome.
DR   PharmGKB; PA37383; -.
DR   VEuPathDB; HostDB:ENSG00000108379; -.
DR   eggNOG; KOG3913; Eukaryota.
DR   GeneTree; ENSGT00940000157854; -.
DR   HOGENOM; CLU_033039_1_0_1; -.
DR   InParanoid; P56703; -.
DR   OMA; WNCTTIE; -.
DR   OrthoDB; 2874082at2759; -.
DR   PhylomeDB; P56703; -.
DR   TreeFam; TF105310; -.
DR   PathwayCommons; P56703; -.
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   SignaLink; P56703; -.
DR   SIGNOR; P56703; -.
DR   BioGRID-ORCS; 7473; 16 hits in 1155 CRISPR screens.
DR   ChiTaRS; WNT3; human.
DR   GeneWiki; WNT3; -.
DR   GenomeRNAi; 7473; -.
DR   Pharos; P56703; Tchem.
DR   PRO; PR:P56703; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P56703; Protein.
DR   Bgee; ENSG00000108379; Expressed in skin of abdomen and 92 other cell types or tissues.
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:1990909; C:Wnt signalosome; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0048018; F:receptor ligand activity; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
DR   GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB.
DR   GO; GO:0044338; P:canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0044339; P:canonical Wnt signaling pathway involved in osteoblast differentiation; IMP:BHF-UCL.
DR   GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR   GO; GO:0000902; P:cell morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
DR   GO; GO:0009950; P:dorsal/ventral axis specification; IEA:Ensembl.
DR   GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl.
DR   GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR   GO; GO:0007276; P:gamete generation; IEA:Ensembl.
DR   GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR   GO; GO:0060323; P:head morphogenesis; IEA:Ensembl.
DR   GO; GO:0060174; P:limb bud formation; IMP:BHF-UCL.
DR   GO; GO:0061180; P:mammary gland epithelium development; IEP:UniProtKB.
DR   GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR   GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IEA:Ensembl.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0048697; P:positive regulation of collateral sprouting in absence of injury; IEA:Ensembl.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR   GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:2000739; P:regulation of mesenchymal stem cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0050767; P:regulation of neurogenesis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0060064; P:Spemann organizer formation at the anterior end of the primitive streak; IEA:Ensembl.
DR   GO; GO:0072089; P:stem cell proliferation; IMP:ParkinsonsUK-UCL.
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:SF82; PROTO-ONCOGENE WNT-3; 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.
DR   Genevisible; P56703; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Developmental protein; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Lipoprotein; Proto-oncogene; Reference proteome; Secreted;
KW   Signal; Wnt signaling pathway.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..355
FT                   /note="Proto-oncogene Wnt-3"
FT                   /id="PRO_0000041416"
FT   LIPID           212
FT                   /note="O-palmitoleoyl serine; by PORCN"
FT                   /evidence="ECO:0000250|UniProtKB:P56704"
FT   CARBOHYD        90
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        80..91
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        131..139
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        141..158
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        206..220
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        208..215
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        284..315
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        300..310
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        314..354
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        330..345
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        332..342
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        337..338
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   HELIX           53..61
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           63..65
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           66..83
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   TURN            84..86
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          87..89
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           98..100
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           110..132
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          153..155
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           162..174
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           182..200
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          203..210
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           211..213
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          217..223
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   HELIX           227..239
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          242..251
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          254..261
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          299..303
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   TURN            310..316
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          319..329
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          333..335
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   TURN            336..338
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          339..341
FT                   /evidence="ECO:0007829|PDB:6AHY"
FT   STRAND          344..355
FT                   /evidence="ECO:0007829|PDB:6AHY"
SQ   SEQUENCE   355 AA;  39645 MW;  85D15F2C7884A64F CRC64;
     MEPHLLGLLL GLLLGGTRVL AGYPIWWSLA LGQQYTSLGS QPLLCGSIPG LVPKQLRFCR
     NYIEIMPSVA EGVKLGIQEC QHQFRGRRWN CTTIDDSLAI FGPVLDKATR ESAFVHAIAS
     AGVAFAVTRS CAEGTSTICG CDSHHKGPPG EGWKWGGCSE DADFGVLVSR EFADARENRP
     DARSAMNKHN NEAGRTTILD HMHLKCKCHG LSGSCEVKTC WWAQPDFRAI GDFLKDKYDS
     ASEMVVEKHR ESRGWVETLR AKYSLFKPPT ERDLVYYENS PNFCEPNPET GSFGTRDRTC
     NVTSHGIDGC DLLCCGRGHN TRTEKRKEKC HCIFHWCCYV SCQECIRIYD VHTCK
//