WNT3_HUMAN
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 03-AUG-2022, entry version 181.
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 -!- 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; 61.
DR IntAct; P56703; 3.
DR STRING; 9606.ENSP00000225512; -.
DR BindingDB; P56703; -.
DR ChEMBL; CHEMBL6079; -.
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; P56703; -.
DR PeptideAtlas; P56703; -.
DR PRIDE; P56703; -.
DR ProteomicsDB; 56936; -.
DR Antibodypedia; 30108; 473 antibodies from 31 providers.
DR DNASU; 7473; -.
DR Ensembl; ENST00000225512.6; ENSP00000225512.5; ENSG00000108379.10.
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 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; GYLMCVC; -.
DR OrthoDB; 965867at2759; -.
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; 14 hits in 1079 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 91 other tissues.
DR Genevisible; P56703; HS.
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:1904954; P:canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0044339; P:canonical Wnt signaling pathway involved in osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:1905474; P:canonical Wnt signaling pathway involved in stem cell proliferation; IDA:ParkinsonsUK-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: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:0030177; P:positive regulation of Wnt signaling pathway; IEA:Ensembl.
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 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; PTHR12027; 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; 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
