WNT2_MOUSE
ID WNT2_MOUSE Reviewed; 360 AA.
AC P21552; Q9CZW3;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Protein Wnt-2;
DE AltName: Full=INT-1-related protein {ECO:0000303|PubMed:2693041};
DE Short=IRP;
DE Flags: Precursor;
GN Name=Wnt2; Synonyms=Irp, Wnt-2;
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=2693041; DOI=10.1242/dev.107.3.643;
RA McMahon J.A., McMahon A.P.;
RT "Nucleotide sequence, chromosomal localization and developmental expression
RT of the mouse int-1-related gene.";
RL Development 107:643-650(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2279700; DOI=10.1101/gad.4.12b.2319;
RA Gavin B.J., McMahon J.A., McMahon A.P.;
RT "Expression of multiple novel Wnt-1/int-1-related genes during fetal and
RT adult mouse development.";
RL Genes Dev. 4:2319-2332(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=19686689; DOI=10.1016/j.devcel.2009.06.005;
RA Goss A.M., Tian Y., Tsukiyama T., Cohen E.D., Zhou D., Lu M.M.,
RA Yamaguchi T.P., Morrisey E.E.;
RT "Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify
RT lung progenitors in the foregut.";
RL Dev. Cell 17:290-298(2009).
RN [7]
RP DEVELOPMENTAL STAGE, AND FUNCTION.
RX PubMed=20018874; DOI=10.1074/jbc.m109.079822;
RA Sousa K.M., Villaescusa J.C., Cajanek L., Ondr J.K., Castelo-Branco G.,
RA Hofstra W., Bryja V., Palmberg C., Bergman T., Wainwright B., Lang R.A.,
RA Arenas E.;
RT "Wnt2 regulates progenitor proliferation in the developing ventral
RT midbrain.";
RL J. Biol. Chem. 285:7246-7253(2010).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21704027; DOI=10.1016/j.ydbio.2011.06.011;
RA Goss A.M., Tian Y., Cheng L., Yang J., Zhou D., Cohen E.D., Morrisey E.E.;
RT "Wnt2 signaling is necessary and sufficient to activate the airway smooth
RT muscle program in the lung by regulating myocardin/Mrtf-B and Fgf10
RT expression.";
RL Dev. Biol. 356:541-552(2011).
CC -!- FUNCTION: Ligand for members of the frizzled family of seven
CC transmembrane receptors. Functions in the canonical Wnt/beta-catenin
CC signaling pathway (PubMed:19686689). Functions as upstream regulator of
CC FGF10 expression (PubMed:19686689). Plays an important role in
CC embryonic lung development (PubMed:19686689). May contribute to
CC embryonic brain development by regulating the proliferation of
CC dopaminergic precursors and neurons (PubMed:20018874).
CC {ECO:0000269|PubMed:19686689, ECO:0000305,
CC ECO:0000305|PubMed:20018874}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250|UniProtKB:P09544}. Secreted
CC {ECO:0000250|UniProtKB:P09544}.
CC -!- TISSUE SPECIFICITY: In embryos in the developing allantois, pericardium
CC heart, and ventral-lateral mesoderm; in adults in lung, brain, heart
CC and placenta.
CC -!- DEVELOPMENTAL STAGE: Detected in ventral mesencephalon from 10.5 to
CC 15.5 dpc; expression levels decrease moderately, but steadily during
CC this period (PubMed:20018874). Detected in the lateral plate mesoderm
CC surrounding the ventral aspect of the anterior foregut from 9.0 to 10.5
CC dpc (PubMed:19686689). Detected in the developing mesenchyme with
CC higher levels surrounding the distal regions of the branching airways
CC from 12.5 to 18.5 dpc (PubMed:19686689). {ECO:0000269|PubMed:19686689,
CC ECO:0000269|PubMed:20018874}.
CC -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC receptors. Depalmitoleoylation leads to Wnt signaling pathway
CC inhibition. {ECO:0000250|UniProtKB:P09544}.
CC -!- DISRUPTION PHENOTYPE: Nearly complete perinatal lethality within
CC minutes after birth, due to lung hypoplasia (PubMed:19686689). About 4%
CC survive for more than 30 days (PubMed:19686689). Combined disruption of
CC Wnt2 and Wnt2b leads to lung agenesis and loss of trachea development
CC (PubMed:19686689). In contrast, development of liver, stomach,
CC intestine, pancreas and kidneys appears grossly normal
CC (PubMed:19686689). {ECO:0000269|PubMed:19686689}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; AK012093; BAB28025.1; -; mRNA.
DR EMBL; CH466533; EDL13868.1; -; Genomic_DNA.
DR EMBL; BC026373; AAH26373.1; -; mRNA.
DR CCDS; CCDS19928.1; -.
DR PIR; B36470; B36470.
DR RefSeq; NP_076142.3; NM_023653.5.
DR AlphaFoldDB; P21552; -.
DR SMR; P21552; -.
DR BioGRID; 204572; 2.
DR STRING; 10090.ENSMUSP00000010941; -.
DR BindingDB; P21552; -.
DR GlyGen; P21552; 1 site.
DR iPTMnet; P21552; -.
DR PhosphoSitePlus; P21552; -.
DR MaxQB; P21552; -.
DR PaxDb; P21552; -.
DR PRIDE; P21552; -.
DR ProteomicsDB; 299995; -.
DR Antibodypedia; 4474; 282 antibodies from 34 providers.
DR DNASU; 22413; -.
DR Ensembl; ENSMUST00000010941; ENSMUSP00000010941; ENSMUSG00000010797.
DR GeneID; 22413; -.
DR KEGG; mmu:22413; -.
DR UCSC; uc009bag.2; mouse.
DR CTD; 7472; -.
DR MGI; MGI:98954; Wnt2.
DR VEuPathDB; HostDB:ENSMUSG00000010797; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000159231; -.
DR HOGENOM; CLU_033039_1_4_1; -.
DR InParanoid; P21552; -.
DR OMA; PKSADWT; -.
DR OrthoDB; 745245at2759; -.
DR PhylomeDB; P21552; -.
DR TreeFam; TF105310; -.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR BioGRID-ORCS; 22413; 4 hits in 72 CRISPR screens.
DR PRO; PR:P21552; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P21552; protein.
DR Bgee; ENSMUSG00000010797; Expressed in prostatic urethra and 112 other tissues.
DR Genevisible; P21552; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031232; C:extrinsic component of external side of plasma membrane; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR GO; GO:0005109; F:frizzled binding; ISO:MGI.
DR GO; GO:0048018; F:receptor ligand activity; ISO:MGI.
DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IMP:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:1904954; P:canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; ISO:MGI.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IMP:MGI.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0033278; P:cell proliferation in midbrain; IMP:CACAO.
DR GO; GO:0007267; P:cell-cell signaling; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0060492; P:lung induction; IGI:MGI.
DR GO; GO:0061180; P:mammary gland epithelium development; IEA:Ensembl.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IDA:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IGI:MGI.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR009140; Wnt2.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01842; WNT2PROTEIN.
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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..360
FT /note="Protein Wnt-2"
FT /id="PRO_0000041411"
FT LIPID 212
FT /note="O-palmitoleoyl serine; by PORCN"
FT /evidence="ECO:0000250|UniProtKB:P56704"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 76..87
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 127..135
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 137..157
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 278..309
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 294..304
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 308..348
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 324..339
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 326..336
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 331..332
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT CONFLICT 232
FT /note="D -> E (in Ref. 1; no nucleotide entry and 2; no
FT nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 40482 MW; 5E37644D3815EEAD CRC64;
MNVPLGGIWL WLPLLLTWLT PEVSSSWWYM RATGGSSRVM CDNVPGLVSR QRQLCHRHPD
VMRAIGLGVA EWTAECQHQF RQHRWNCNTL DRDHSLFGRV LLRSSRESAF VYAISSAGVV
FAITRACSQG ELKSCSCDPK KKGSAKDSKG TFDWGGCSDN IDYGIKFARA FVDAKERKGK
DARALMNLHN NRAGRKAVKR FLKQECKCHG VSGSCTLRTC WLAMADFRKT GDYLWRKYNG
AIQVVMNQDG TGFTVANKRF KKPTKNDLVY FENSPDYCIR DREAGSLGTA GRVCNLTSRG
MDSCEVMCCG RGYDTSHVTR MTKCECKFHW CCAVRCQDCL EALDVHTCKA PKSADWATPT
