ID WNT3_MOUSE Reviewed; 355 AA.
AC P17553;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 27-MAR-2024, entry version 184.
DE RecName: Full=Proto-oncogene Wnt-3;
DE AltName: Full=Proto-oncogene Int-4;
DE Flags: Precursor;
GN Name=Wnt3; Synonyms=Int-4, Wnt-3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Embryo;
RX PubMed=2162045; DOI=10.1073/pnas.87.12.4519;
RA Roelink H., Wagenaar E., Lopes da Silva S., Nusse R.;
RT "Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is
RT homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and
RT adult brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:4519-4523(1990).
RN [2]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=10431240; DOI=10.1038/11932;
RA Liu P., Wakamiya M., Shea M.J., Albrecht U., Behringer R.R., Bradley A.;
RT "Requirement for Wnt3 in vertebrate axis formation.";
RL Nat. Genet. 22:361-365(1999).
RN [3]
RP INTERACTION WITH PORCN.
RX PubMed=10866835; DOI=10.1046/j.1432-1033.2000.01478.x;
RA Tanaka K., Okabayashi H., Asashima M., Perrimon N., Kadowaki T.;
RT "The evolutionarily conserved porcupine gene family is involved in the
RT processing of the Wnt family.";
RL Eur. J. Biochem. 267:4300-4311(2000).
RN [4]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=12569130; DOI=10.1101/gad.1044903;
RA Barrow J.R., Thomas K.R., Boussadia-Zahui O., Moore R., Kemler R.,
RA Capecchi M.R., McMahon A.P.;
RT "Ectodermal Wnt3/beta-catenin signaling is required for the establishment
RT and maintenance of the apical ectodermal ridge.";
RL Genes Dev. 17:394-409(2003).
RN [5]
RP INTERACTION WITH WLS, AND DEVELOPMENTAL STAGE.
RX PubMed=19841259; DOI=10.1073/pnas.0904894106;
RA Fu J., Jiang M., Mirando A.J., Yu H.-M., Hsu W.;
RT "Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for
RT embryonic axis formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:18598-18603(2009).
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 (By similarity). Required for normal
CC gastrulation, formation of the primitive streak, and for the formation
CC of the mesoderm during early embryogenesis (PubMed:10431240). Required
CC for normal formation of the apical ectodermal ridge and for normal
CC embryonic limb development (PubMed:12569130).
CC {ECO:0000250|UniProtKB:P56703, ECO:0000269|PubMed:10431240,
CC ECO:0000269|PubMed:12569130, ECO:0000305}.
CC -!- SUBUNIT: Forms a soluble 1:1 complex with AFM; this prevents
CC oligomerization and is required for prolonged biological activity. The
CC complex with AFM may represent the physiological form in body fluids
CC (By similarity). Interacts with PORCN (PubMed:10866835). Interacts with
CC WLS (PubMed:19841259). {ECO:0000250|UniProtKB:P56703,
CC ECO:0000269|PubMed:10866835, ECO:0000269|PubMed:19841259}.
CC -!- INTERACTION:
CC P17553; O35082: Kl; NbExp=4; IntAct=EBI-1570853, EBI-1570828;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:P56703}. Secreted
CC {ECO:0000250|UniProtKB:P56703}.
CC -!- TISSUE SPECIFICITY: Detected at low levels in adult brain
CC (PubMed:2162045). Dorsal portion of the neural tube, dorsal ectoderm,
CC the branchial arches, and the limb buds. {ECO:0000269|PubMed:2162045}.
CC -!- DEVELOPMENTAL STAGE: Detected at 6.25 to 7.5 dpc in primitive streak,
CC proximal epiblast, visceral endoderm and at the junction between the
CC embryonic and extraembryonic ectoderm, with higher levels in the
CC posterior region (PubMed:10431240, PubMed:19841259). Detected in the
CC ectoderm at forelimb buds at 9.5 dpc (PubMed:12569130). Detected in all
CC outgrowing limbs and in ectoderm flanking the limbs at least till 11.5
CC dpc (PubMed:12569130). Highly expressed in embryos at 11.5 and 12.5
CC dpc, with very low expression levels before and after this period
CC (PubMed:2162045). {ECO:0000269|PubMed:10431240,
CC ECO:0000269|PubMed:12569130, ECO:0000269|PubMed:19841259,
CC ECO:0000269|PubMed:2162045}.
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 -!- MISCELLANEOUS: Some mouse mammary tumors induced by mouse mammary tumor
CC virus (MMTV) contain a provirus integrated into a host cell region
CC which has been named Wnt3. {ECO:0000269|PubMed:2162045}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; M32502; AAB38109.1; -; mRNA.
DR CCDS; CCDS25523.1; -.
DR PIR; A35503; A35503.
DR RefSeq; NP_033547.1; NM_009521.2.
DR AlphaFoldDB; P17553; -.
DR SMR; P17553; -.
DR BioGRID; 204574; 3.
DR DIP; DIP-39897N; -.
DR IntAct; P17553; 2.
DR STRING; 10090.ENSMUSP00000000127; -.
DR GlyCosmos; P17553; 2 sites, No reported glycans.
DR GlyGen; P17553; 2 sites.
DR PhosphoSitePlus; P17553; -.
DR SwissPalm; P17553; -.
DR MaxQB; P17553; -.
DR PaxDb; 10090-ENSMUSP00000000127; -.
DR ProteomicsDB; 297854; -.
DR Antibodypedia; 30108; 517 antibodies from 31 providers.
DR DNASU; 22415; -.
DR Ensembl; ENSMUST00000000127.6; ENSMUSP00000000127.6; ENSMUSG00000000125.6.
DR GeneID; 22415; -.
DR KEGG; mmu:22415; -.
DR UCSC; uc007lvs.2; mouse.
DR AGR; MGI:98955; -.
DR CTD; 7473; -.
DR MGI; MGI:98955; Wnt3.
DR VEuPathDB; HostDB:ENSMUSG00000000125; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000157854; -.
DR HOGENOM; CLU_033039_1_0_1; -.
DR InParanoid; P17553; -.
DR OMA; WNCTTIE; -.
DR OrthoDB; 2874082at2759; -.
DR PhylomeDB; P17553; -.
DR TreeFam; TF105310; -.
DR Reactome; R-MMU-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR BioGRID-ORCS; 22415; 1 hit in 80 CRISPR screens.
DR PRO; PR:P17553; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P17553; Protein.
DR Bgee; ENSMUSG00000000125; Expressed in external ectoderm and 74 other cell types or tissues.
DR ExpressionAtlas; P17553; baseline and differential.
DR Genevisible; P17553; MM.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005109; F:frizzled binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; TAS:MGI.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:MGI.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IDA:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0044338; P:canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation; ISO:MGI.
DR GO; GO:1904954; P:canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; ISO:MGI.
DR GO; GO:0044339; P:canonical Wnt signaling pathway involved in osteoblast differentiation; ISO:MGI.
DR GO; GO:1905474; P:canonical Wnt signaling pathway involved in stem cell proliferation; ISO:MGI.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0000902; P:cell morphogenesis; ISO:MGI.
DR GO; GO:0007267; P:cell-cell signaling; TAS:MGI.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0007276; P:gamete generation; IGI:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0060323; P:head morphogenesis; IGI:MGI.
DR GO; GO:0060174; P:limb bud formation; ISO:MGI.
DR GO; GO:0060173; P:limb development; IMP:MGI.
DR GO; GO:0061180; P:mammary gland epithelium development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IDA:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0048697; P:positive regulation of collateral sprouting in absence of injury; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IDA:CACAO.
DR GO; GO:2000739; P:regulation of mesenchymal stem cell differentiation; ISO:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:0060064; P:Spemann organizer formation at the anterior end of the primitive streak; IMP:MGI.
DR GO; GO:0072089; P:stem cell proliferation; ISO:MGI.
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.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Lipoprotein; Proto-oncogene; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..355
FT /note="Proto-oncogene Wnt-3"
FT /id="PRO_0000041417"
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"
SQ SEQUENCE 355 AA; 39659 MW; F31CFD65E43E9C17 CRC64;
MEPHLLGLLL GLLLSGTRVL AGYPIWWSLA LGQQYTSLAS QPLLCGSIPG LVPKQLRFCR
NYIEIMPSVA EGVKLGIQEC QHQFRGRRWN CTTIDDSLAI FGPVLDKATR ESAFVHAIAS
AGVAFAVTRS CAEGTSTICG CDSHHKGPPG EGWKWGGCSE DADFGVLVSR EFADARENRP
DARSAMNKHN NEAGRTTILD HMHLKCKCHG LSGSCEVKTC WWAQPDFRAI GDFLKDKYDS
ASEMVVEKHR ESRGWVETLR AKYALFKPPT ERDLVYYENS PNFCEPNPET GSFGTRDRTC
NVTSHGIDGC DLLCCGRGHN TRTEKRKEKC HCVFHWCCYV SCQECIRIYD VHTCK
//
