WNT9A_HUMAN
ID WNT9A_HUMAN Reviewed; 365 AA.
AC O14904; A6NLW2; Q2M2J3; Q5VWU0; Q96S50;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Protein Wnt-9a;
DE AltName: Full=Protein Wnt-14;
DE Flags: Precursor;
GN Name=WNT9A; Synonyms=WNT14;
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].
RX PubMed=11414706; DOI=10.1006/bbrc.2001.5105;
RA Saitoh T., Hirai M., Katoh M.;
RT "Molecular cloning and characterization of WNT3a and WNT14 clustered in
RT human chromosome 1q42 region.";
RL Biochem. Biophys. Res. Commun. 284:1168-1175(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 221-343.
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 [6]
RP INTERACTION WITH AFM, 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. Functions in the canonical Wnt/beta-catenin
CC signaling pathway. Required for normal timing of IHH expression during
CC embryonic bone development, normal chondrocyte maturation and for
CC normal bone mineralization during embryonic bone development. Plays a
CC redundant role in maintaining joint integrity.
CC {ECO:0000250|UniProtKB:O42280, ECO:0000250|UniProtKB:Q8R5M2}.
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). {ECO:0000269|PubMed:26902720}.
CC -!- INTERACTION:
CC O14904; O43829: ZBTB14; NbExp=3; IntAct=EBI-12053451, EBI-10176632;
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 -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; AB060283; BAB61051.1; -; mRNA.
DR EMBL; AL360269; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69821.1; -; Genomic_DNA.
DR EMBL; BC111960; AAI11961.1; -; mRNA.
DR EMBL; BC113431; AAI13432.1; -; mRNA.
DR EMBL; AF028702; AAC39550.1; -; Genomic_DNA.
DR CCDS; CCDS31045.1; -.
DR RefSeq; NP_003386.1; NM_003395.2.
DR AlphaFoldDB; O14904; -.
DR SMR; O14904; -.
DR BioGRID; 113320; 3.
DR IntAct; O14904; 3.
DR STRING; 9606.ENSP00000272164; -.
DR GlyGen; O14904; 1 site.
DR PhosphoSitePlus; O14904; -.
DR BioMuta; WNT9A; -.
DR jPOST; O14904; -.
DR MassIVE; O14904; -.
DR PaxDb; O14904; -.
DR PeptideAtlas; O14904; -.
DR PRIDE; O14904; -.
DR ProteomicsDB; 48289; -.
DR Antibodypedia; 2495; 243 antibodies from 29 providers.
DR DNASU; 7483; -.
DR Ensembl; ENST00000272164.6; ENSP00000272164.5; ENSG00000143816.8.
DR GeneID; 7483; -.
DR KEGG; hsa:7483; -.
DR MANE-Select; ENST00000272164.6; ENSP00000272164.5; NM_003395.4; NP_003386.1.
DR UCSC; uc001hri.3; human.
DR CTD; 7483; -.
DR DisGeNET; 7483; -.
DR GeneCards; WNT9A; -.
DR HGNC; HGNC:12778; WNT9A.
DR HPA; ENSG00000143816; Tissue enhanced (skeletal).
DR MIM; 602863; gene.
DR neXtProt; NX_O14904; -.
DR OpenTargets; ENSG00000143816; -.
DR PharmGKB; PA37379; -.
DR VEuPathDB; HostDB:ENSG00000143816; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000159618; -.
DR HOGENOM; CLU_033039_2_0_1; -.
DR InParanoid; O14904; -.
DR OMA; AGRKCHR; -.
DR OrthoDB; 866763at2759; -.
DR PhylomeDB; O14904; -.
DR TreeFam; TF105310; -.
DR PathwayCommons; O14904; -.
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 Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR SignaLink; O14904; -.
DR SIGNOR; O14904; -.
DR BioGRID-ORCS; 7483; 14 hits in 1071 CRISPR screens.
DR ChiTaRS; WNT9A; human.
DR GeneWiki; WNT9A; -.
DR GenomeRNAi; 7483; -.
DR Pharos; O14904; Tbio.
DR PRO; PR:O14904; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O14904; protein.
DR Bgee; ENSG00000143816; Expressed in decidua and 140 other tissues.
DR ExpressionAtlas; O14904; baseline and differential.
DR Genevisible; O14904; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IBA:GO_Central.
DR GO; GO:0048018; F:receptor ligand activity; IDA:WormBase.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:WormBase.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
DR GO; GO:0061303; P:cornea development in camera-type eye; ISS:BHF-UCL.
DR GO; GO:0072498; P:embryonic skeletal joint development; ISS:BHF-UCL.
DR GO; GO:0061072; P:iris morphogenesis; ISS:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:BHF-UCL.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR013303; Wnt9a.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR PANTHER; PTHR12027:SF75; PTHR12027:SF75; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01894; WNT14PROTEIN.
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; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..365
FT /note="Protein Wnt-9a"
FT /id="PRO_0000041455"
FT REGION 260..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 221
FT /note="O-palmitoleoyl serine; by PORCN"
FT /evidence="ECO:0000250|UniProtKB:P56704"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 93..104
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 141..149
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 151..168
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 215..229
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 217..224
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 299..324
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 313..319
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 323..363
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 339..354
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 341..351
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 346..347
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT VARIANT 260
FT /note="A -> T (in dbSNP:rs8192633)"
FT /id="VAR_052956"
SQ SEQUENCE 365 AA; 40320 MW; 1E1284D744C6A9B2 CRC64;
MLDGSPLARW LAAAFGLTLL LAALRPSAAY FGLTGSEPLT ILPLTLEPEA AAQAHYKACD
RLKLERKQRR MCRRDPGVAE TLVEAVSMSA LECQFQFRFE RWNCTLEGRY RASLLKRGFK
ETAFLYAISS AGLTHALAKA CSAGRMERCT CDEAPDLENR EAWQWGGCGD NLKYSSKFVK
EFLGRRSSKD LRARVDFHNN LVGVKVIKAG VETTCKCHGV SGSCTVRTCW RQLAPFHEVG
KHLKHKYETA LKVGSTTNEA AGEAGAISPP RGRASGAGGS DPLPRTPELV HLDDSPSFCL
AGRFSPGTAG RRCHREKNCE SICCGRGHNT QSRVVTRPCQ CQVRWCCYVE CRQCTQREEV
YTCKG
