WNT9B_MOUSE
ID WNT9B_MOUSE Reviewed; 359 AA.
AC O35468; Q8VI90;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Protein Wnt-9b;
DE AltName: Full=Protein Wnt-14b {ECO:0000303|PubMed:11786923};
DE AltName: Full=Protein Wnt-15 {ECO:0000303|PubMed:9441749};
DE Flags: Precursor;
GN Name=Wnt9b;
GN Synonyms=Wnt14b {ECO:0000303|PubMed:11786923},
GN Wnt15 {ECO:0000303|PubMed:9441749};
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].
RX PubMed=11786923;
RA Kirikoshi H., Katoh M.;
RT "Molecular cloning and characterization of mouse Wnt14b, clustered with
RT mouse Wnt3 in mouse chromosome 11.";
RL Int. J. Mol. Med. 9:135-139(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=12573259; DOI=10.1016/s0888-7543(02)00012-5;
RA Qian J., Jiang Z., Li M., Heaphy P., Liu Y.H., Shackleford G.M.;
RT "Mouse Wnt9b transforming activity, tissue-specific expression, and
RT evolution.";
RL Genomics 81:34-46(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 211-310.
RX PubMed=9441749; DOI=10.1006/geno.1997.5041;
RA Bergstein I., Eisenberg L.M., Bhalerao J., Jenkins N.A., Copeland N.G.,
RA Osborne M.P., Bowcock A.M., Brown A.M.C.;
RT "Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is
RT closely linked to WNT3 on human chromosome 17q21.";
RL Genomics 46:450-458(1997).
RN [4]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16054034; DOI=10.1016/j.devcel.2005.05.016;
RA Carroll T.J., Park J.S., Hayashi S., Majumdar A., McMahon A.P.;
RT "Wnt9b plays a central role in the regulation of mesenchymal to epithelial
RT transitions underlying organogenesis of the mammalian urogenital system.";
RL Dev. Cell 9:283-292(2005).
RN [5]
RP FUNCTION.
RX PubMed=17537789; DOI=10.1242/dev.006155;
RA Park J.S., Valerius M.T., McMahon A.P.;
RT "Wnt/beta-catenin signaling regulates nephron induction during mouse kidney
RT development.";
RL Development 134:2533-2539(2007).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22461561; DOI=10.1242/dev.075796;
RA Jin Y.R., Han X.H., Taketo M.M., Yoon J.K.;
RT "Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and
RT maxillary processes during upper jaw and lip development.";
RL Development 139:1821-1830(2012).
RN [7]
RP DISEASE, FUNCTION, AND DEVELOPMENTAL STAGE.
RC STRAIN=A/WySn {ECO:0000303|PubMed:25257647};
RX PubMed=25257647; DOI=10.1002/bdra.23320;
RA Juriloff D.M., Harris M.J., Mager D.L., Gagnier L.;
RT "Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip
RT and palate in the A/WySn mouse strain.";
RL Birth Defects Res. A Clin. Mol. Teratol. 100:772-788(2014).
CC -!- FUNCTION: Ligand for members of the frizzled family of seven
CC transmembrane receptors (Probable). Functions in the canonical
CC Wnt/beta-catenin signaling pathway (PubMed:22461561, PubMed:16054034,
CC PubMed:17537789). Required for normal embryonic kidney development, and
CC for normal development of the urogenital tract, including uterus and
CC part of the oviduct and the upper vagina in females, and epididymis and
CC vas deferens in males (PubMed:16054034). Activates a signaling cascade
CC in the metanephric mesenchyme that induces tubulogenesis
CC (PubMed:16054034, PubMed:17537789). Acts upstream of WNT4 in the
CC signaling pathways that mediate development of kidney tubules and the
CC Muellerian ducts (PubMed:16054034). Plays a role in cranofacial
CC development and is required for normal fusion of the palate during
CC embryonic development (PubMed:16054034, PubMed:22461561,
CC PubMed:25257647). {ECO:0000269|PubMed:16054034,
CC ECO:0000269|PubMed:17537789, ECO:0000269|PubMed:22461561,
CC ECO:0000269|PubMed:25257647, 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 Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a
CC WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the
CC complex with LRP6. Interacts with PKD1 (via extracellular domain).
CC {ECO:0000250|UniProtKB:O14905}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:O14905}. Secreted
CC {ECO:0000250|UniProtKB:O14905}.
CC -!- DEVELOPMENTAL STAGE: Detected throughout the Wolffian duct epithelium
CC from 9.5 dpc to 14.5 dpc. Detected in the stalk region of the ureteric
CC bud at 10.5 to 11.0 dpc. Continues to be expressed in the developing
CC collecting duct system throughout nephrogenesis, but is not detected at
CC branching tips. Within the urogenital tract, expression is restricted
CC to the kidney at 15.5 dpc (PubMed:16054034). Detected in embryonic head
CC from early headfold stages to at least 12 dpc.
CC {ECO:0000269|PubMed:16054034, ECO:0000269|PubMed:25257647}.
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: Note=Spontaneous insertion of a retrotransposon in the Wnt9b
CC promoter region causes reduced Wnt9b expression. Decreased Wnt9b
CC expression is correlated with increased incidence of cleft lip and
CC palate. {ECO:0000269|PubMed:25257647}.
CC -!- DISRUPTION PHENOTYPE: Complete perinatal lethality. All pups die within
CC the first 24 hours after birth (PubMed:16054034). Mutant pups lack
CC kidneys. In addition, females have normal ovaries, but no uterus. Males
CC have testes, but lack the epididymis (PubMed:16054034). The early
CC stages of the development of the ureteric component of the metanephric
CC kidney appear normal, but branching after the T-stage is disrupted, and
CC mutants lack mesonephric tubules at 11.5 dpc (PubMed:16054034). Mutant
CC embryos have a cleft lip and palate phenotype at 18.5 dpc, plus
CC additional, bilateral defects in upper jaw skeleton development
CC (PubMed:16054034, PubMed:22461561). Embryos appear normal at 10.5 dpc,
CC but display hypoplasia of the lateral and medial nasal process at 11
CC dpc. At 11.5 dpc, they display a clear bilateral gap between the medial
CC nasal process and the fused medial end of the lateral nasal process and
CC the maxillary process. The palatal shelves display lack of midline
CC contact at 14.5 dpc. {ECO:0000269|PubMed:16054034,
CC ECO:0000269|PubMed:22461561}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; AB073819; BAB83866.1; -; mRNA.
DR EMBL; AF469004; AAL82385.1; -; mRNA.
DR EMBL; AF031169; AAC39950.1; -; Genomic_DNA.
DR CCDS; CCDS25522.1; -.
DR RefSeq; NP_035849.3; NM_011719.4.
DR AlphaFoldDB; O35468; -.
DR SMR; O35468; -.
DR DIP; DIP-59409N; -.
DR IntAct; O35468; 2.
DR MINT; O35468; -.
DR STRING; 10090.ENSMUSP00000018630; -.
DR GlyGen; O35468; 1 site.
DR PhosphoSitePlus; O35468; -.
DR PaxDb; O35468; -.
DR PRIDE; O35468; -.
DR Antibodypedia; 17705; 167 antibodies from 34 providers.
DR DNASU; 22412; -.
DR Ensembl; ENSMUST00000018630; ENSMUSP00000018630; ENSMUSG00000018486.
DR GeneID; 22412; -.
DR KEGG; mmu:22412; -.
DR UCSC; uc007lvr.1; mouse.
DR CTD; 7484; -.
DR MGI; MGI:1197020; Wnt9b.
DR VEuPathDB; HostDB:ENSMUSG00000018486; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000158599; -.
DR HOGENOM; CLU_033039_2_0_1; -.
DR InParanoid; O35468; -.
DR OMA; RLELWVP; -.
DR OrthoDB; 866763at2759; -.
DR PhylomeDB; O35468; -.
DR TreeFam; TF105310; -.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR BioGRID-ORCS; 22412; 3 hits in 73 CRISPR screens.
DR PRO; PR:O35468; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O35468; protein.
DR Bgee; ENSMUSG00000018486; Expressed in interventricular septum and 86 other tissues.
DR ExpressionAtlas; O35468; baseline and differential.
DR Genevisible; O35468; MM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; IC:ParkinsonsUK-UCL.
DR GO; GO:0039706; F:co-receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005109; F:frizzled binding; IBA:GO_Central.
DR GO; GO:0048018; F:receptor ligand activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IMP:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IEP:MGI.
DR GO; GO:0072044; P:collecting duct development; IMP:MGI.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR GO; GO:0072046; P:establishment of planar polarity involved in nephron morphogenesis; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0060993; P:kidney morphogenesis; IMP:MGI.
DR GO; GO:0072003; P:kidney rudiment formation; IMP:MGI.
DR GO; GO:0030539; P:male genitalia development; IMP:MGI.
DR GO; GO:0072038; P:mesenchymal stem cell maintenance involved in nephron morphogenesis; IMP:MGI.
DR GO; GO:0072181; P:mesonephric duct formation; IMP:MGI.
DR GO; GO:0072164; P:mesonephric tubule development; IMP:MGI.
DR GO; GO:0072170; P:metanephric tubule development; IMP:MGI.
DR GO; GO:0072174; P:metanephric tubule formation; IMP:MGI.
DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; ISO:MGI.
DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; ISO:MGI.
DR GO; GO:0072078; P:nephron tubule morphogenesis; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:1905438; P:non-canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; ISO:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:MGI.
DR GO; GO:0009786; P:regulation of asymmetric cell division; IMP:MGI.
DR GO; GO:0003339; P:regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; IDA:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0035150; P:regulation of tube size; IMP:MGI.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:0061038; P:uterus morphogenesis; IMP:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IMP:MGI.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IMP:MGI.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR026535; WNT9B.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR PANTHER; PTHR12027:SF84; PTHR12027:SF84; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01349; WNTPROTEIN.
DR SMART; SM00097; WNT1; 1.
DR PROSITE; PS00246; WNT1; 1.
PE 2: Evidence at transcript level;
KW Developmental protein; Disulfide bond; Extracellular matrix; Glycoprotein;
KW Lipoprotein; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..359
FT /note="Protein Wnt-9b"
FT /id="PRO_0000041459"
FT LIPID 218
FT /note="O-palmitoleoyl serine; by PORCN"
FT /evidence="ECO:0000250|UniProtKB:P56704"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 91..102
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 137..145
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 147..164
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 212..226
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 214..221
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 293..318
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 307..313
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 317..357
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 333..348
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 335..345
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 340..341
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT CONFLICT 310
FT /note="D -> G (in Ref. 3; AAC39950)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 38982 MW; C98D7B5F566B70F5 CRC64;
MRPAPALALA ALCLLVLPAA AAAAAYFGLT GREVLTPFPG LGTAAAPAQA GAHLKQCDLL
KLSRRQKQLC RREPGLAETL RDAAHLGLLE CQFQFRQERW NCSLEGRTGL LQRGFKETAF
LYAVSAAALT HALARACSAG RMERCTCDDS PGLESRQAWQ WGVCGDNLKY STKFLSNFLG
PKRGSKDLRA RADAHNTHVG IKAVKSGLRT TCKCHGVSGS CAVRTCWKQL SPFRETGQVL
KLRYDTAVKV SSATNEALGR LELWAPAKPG GPAKGLAPRP GDLVYMEDSP SFCRPSKYSP
GTAGRVCSRD SSCSSLCCGR GYDTQSRMVV FSCHCQVQWC CYVECQQCAQ QELVYTCKR
