ID WNT2_HUMAN Reviewed; 360 AA. AC P09544; A4D0V1; Q75N05; Q9UDP9; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 24-JAN-2024, entry version 202. DE RecName: Full=Protein Wnt-2; DE AltName: Full=Int-1-like protein 1; DE AltName: Full=Int-1-related protein; DE Short=IRP; DE Flags: Precursor; GN Name=WNT2; Synonyms=INT1L1, IRP; 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]. RC TISSUE=Lung; RX PubMed=2971536; DOI=10.1002/j.1460-2075.1988.tb03003.x; RA Wainwright B.J., Scambler P.J., Stanier P., Watson E.K., Bell G., RA Wicking C., Estivill X., Courtney M., Boue A., Pedersen P.S., RA Williamson R., Farrall M.; RT "Isolation of a human gene with protein sequence similarity to human and RT murine int-1 and the Drosophila segment polarity mutant wingless."; RL EMBO J. 7:1743-1748(1988). RN [2] RP SEQUENCE REVISION. RA Farrall M.; RL Submitted (APR-1988) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Lung, and Testis; 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 [9] RP FUNCTION, SUBCELLULAR LOCATION, AND PALMITOLEOYLATION. 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 [10] RP VARIANTS ARG-5 AND TRP-299, AND TISSUE SPECIFICITY. RX PubMed=11449391; DOI=10.1002/ajmg.1401; RA Wassink T.H., Piven J., Vieland V.J., Huang J., Swiderski R.E., Pietila J., RA Braun T., Beck G., Folstein S.E., Haines J.L., Sheffield V.C.; RT "Evidence supporting WNT2 as an autism susceptibility gene."; RL Am. J. Med. Genet. 105:406-413(2001). RN [11] RP SHOWS THAT WNT2 IS NOT LINKED TO AUTISM SUSCEPTIBILITY. RX PubMed=11840514; DOI=10.1002/ajmg.10182; RA McCoy P.A., Shao Y., Wolpert C.M., Donnelly S.L., Ashley-Koch A., RA Abel H.L., Ravan S.A., Abramson R.K., Wright H.H., DeLong G.R., RA Cuccaro M.L., Gilbert J.R., Pericak-Vance M.A.; RT "No association between the WNT2 gene and autistic disorder."; RL Am. J. Med. Genet. 114:106-109(2002). CC -!- FUNCTION: Ligand for members of the frizzled family of seven CC transmembrane receptors. Functions in the canonical Wnt signaling CC pathway that results in activation of transcription factors of the CC TCF/LEF family (PubMed:20018874). Functions as a upstream regulator of CC FGF10 expression. Plays an important role in embryonic lung CC development. May contribute to embryonic brain development by CC regulating the proliferation of dopaminergic precursors and neurons (By CC similarity). {ECO:0000250|UniProtKB:P21552, CC ECO:0000269|PubMed:20018874}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000305}. Secreted {ECO:0000269|PubMed:20018874}. CC -!- TISSUE SPECIFICITY: Expressed in brain in the thalamus, in fetal and CC adult lung and in placenta. {ECO:0000269|PubMed:11449391}. CC -!- PTM: Palmitoleoylation is required for efficient binding to frizzled CC receptors. Depalmitoleoylation leads to Wnt signaling pathway CC inhibition. {ECO:0000269|PubMed:20018874}. CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07876; CAA30725.1; -; mRNA. DR EMBL; AK056742; BAG51800.1; -; mRNA. DR EMBL; BT019608; AAV38415.1; -; mRNA. DR EMBL; AC002465; AAB67043.1; -; Genomic_DNA. DR EMBL; AC006326; AAD28351.1; -; Genomic_DNA. DR EMBL; CH236947; EAL24355.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83525.1; -; Genomic_DNA. DR EMBL; BC029854; AAH29854.1; -; mRNA. DR EMBL; BC078170; AAH78170.1; -; mRNA. DR CCDS; CCDS5771.1; -. DR PIR; S00834; S00834. DR RefSeq; NP_003382.1; NM_003391.2. DR AlphaFoldDB; P09544; -. DR SMR; P09544; -. DR BioGRID; 113309; 26. DR IntAct; P09544; 7. DR STRING; 9606.ENSP00000265441; -. DR ChEMBL; CHEMBL1255132; -. DR GlyCosmos; P09544; 1 site, No reported glycans. DR GlyGen; P09544; 1 site. DR iPTMnet; P09544; -. DR PhosphoSitePlus; P09544; -. DR BioMuta; WNT2; -. DR DMDM; 139750; -. DR MassIVE; P09544; -. DR PaxDb; 9606-ENSP00000265441; -. DR PeptideAtlas; P09544; -. DR ProteomicsDB; 52246; -. DR ABCD; P09544; 5 sequenced antibodies. DR Antibodypedia; 4474; 322 antibodies from 34 providers. DR DNASU; 7472; -. DR Ensembl; ENST00000265441.8; ENSP00000265441.3; ENSG00000105989.10. DR GeneID; 7472; -. DR KEGG; hsa:7472; -. DR MANE-Select; ENST00000265441.8; ENSP00000265441.3; NM_003391.3; NP_003382.1. DR UCSC; uc003viz.4; human. DR AGR; HGNC:12780; -. DR CTD; 7472; -. DR DisGeNET; 7472; -. DR GeneCards; WNT2; -. DR HGNC; HGNC:12780; WNT2. DR HPA; ENSG00000105989; Tissue enriched (placenta). DR MIM; 147870; gene. DR neXtProt; NX_P09544; -. DR OpenTargets; ENSG00000105989; -. DR PharmGKB; PA37381; -. DR VEuPathDB; HostDB:ENSG00000105989; -. DR eggNOG; KOG3913; Eukaryota. DR GeneTree; ENSGT00940000159231; -. DR HOGENOM; CLU_033039_1_4_1; -. DR InParanoid; P09544; -. DR OMA; ITRMTKC; -. DR OrthoDB; 2874082at2759; -. DR PhylomeDB; P09544; -. DR TreeFam; TF105310; -. DR PathwayCommons; P09544; -. DR Reactome; R-HSA-3238698; WNT ligand biogenesis and trafficking. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR SignaLink; P09544; -. DR SIGNOR; P09544; -. DR BioGRID-ORCS; 7472; 8 hits in 1146 CRISPR screens. DR GeneWiki; WNT2; -. DR GenomeRNAi; 7472; -. DR Pharos; P09544; Tbio. DR PRO; PR:P09544; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P09544; Protein. DR Bgee; ENSG00000105989; Expressed in stromal cell of endometrium and 111 other cell types or tissues. DR ExpressionAtlas; P09544; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:1990909; C:Wnt signalosome; IC:ParkinsonsUK-UCL. DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL. DR GO; GO:0005109; F:frizzled binding; IPI:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IEA:Ensembl. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central. DR GO; GO:0033278; P:cell proliferation in midbrain; IDA:ParkinsonsUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; IDA:BHF-UCL. DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:UniProtKB. DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl. DR GO; GO:0061072; P:iris morphogenesis; ISS:BHF-UCL. DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl. DR GO; GO:0002088; P:lens development in camera-type eye; ISS:BHF-UCL. DR GO; GO:0060492; P:lung induction; IEA:Ensembl. DR GO; GO:0061180; P:mammary gland epithelium development; IEP:UniProtKB. DR GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; IDA:ParkinsonsUK-UCL. DR GO; GO:0022008; P:neurogenesis; TAS:ParkinsonsUK-UCL. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL. DR CDD; cd19345; Wnt_Wnt2; 1. 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:SF86; PROTEIN WNT-2; 1. DR PANTHER; PTHR12027; WNT RELATED; 1. DR Pfam; PF00110; wnt; 1. DR PRINTS; PR01842; WNT2PROTEIN. DR PRINTS; PR01349; WNTPROTEIN. DR SMART; SM00097; WNT1; 1. DR PROSITE; PS00246; WNT1; 1. DR Genevisible; P09544; HS. 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_0000041410" 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 VARIANT 5 FT /note="L -> R (in dbSNP:rs145839592)" FT /evidence="ECO:0000269|PubMed:11449391" FT /id="VAR_013865" FT VARIANT 294 FT /note="C -> F (in dbSNP:rs1051751)" FT /id="VAR_052954" FT VARIANT 299 FT /note="R -> W (in dbSNP:rs148046128)" FT /evidence="ECO:0000269|PubMed:11449391" FT /id="VAR_013866" SQ SEQUENCE 360 AA; 40418 MW; AA96325BF68C4788 CRC64; MNAPLGGIWL WLPLLLTWLT PEVNSSWWYM RATGGSSRVM CDNVPGLVSS QRQLCHRHPD VMRAISQGVA EWTAECQHQF RQHRWNCNTL DRDHSLFGRV LLRSSRESAF VYAISSAGVV FAITRACSQG EVKSCSCDPK KMGSAKDSKG IFDWGGCSDN IDYGIKFARA FVDAKERKGK DARALMNLHN NRAGRKAVKR FLKQECKCHG VSGSCTLRTC WLAMADFRKT GDYLWRKYNG AIQVVMNQDG TGFTVANERF KKPTKNDLVY FENSPDYCIR DREAGSLGTA GRVCNLTSRG MDSCEVMCCG RGYDTSHVTR MTKCGCKFHW CCAVRCQDCL EALDVHTCKA PKNADWTTAT //