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WNT5A_RABIT
ID   WNT5A_RABIT             Reviewed;         380 AA.
AC   Q27Q52;
DT   14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 1.
DT   03-AUG-2022, entry version 83.
DE   RecName: Full=Protein Wnt-5a {ECO:0000303|PubMed:16754689};
DE   Flags: Precursor;
GN   Name=WNT5A {ECO:0000303|PubMed:16754689};
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:ABD47459.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RC   TISSUE=Articular cartilage {ECO:0000312|EMBL:ABD47459.1};
RX   PubMed=16754689; DOI=10.1074/jbc.m601804200;
RA   Ryu J.-H., Chun J.-S.;
RT   "Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of
RT   type II collagen expression in articular chondrocytes.";
RL   J. Biol. Chem. 281:22039-22047(2006).
CC   -!- FUNCTION: Ligand for members of the frizzled family of seven
CC       transmembrane receptors. Can activate or inhibit canonical Wnt
CC       signaling, depending on receptor context. In the presence of FZD4,
CC       activates beta-catenin signaling. In the presence of ROR2, inhibits the
CC       canonical Wnt pathway by promoting beta-catenin degradation through a
CC       GSK3-independent pathway which involves down-regulation of beta-
CC       catenin-induced reporter gene expression (By similarity). Suppression
CC       of the canonical pathway allows chondrogenesis to occur
CC       (PubMed:16754689). Inhibits tumor formation. Stimulates cell migration.
CC       Decreases proliferation, migration, invasiveness and clonogenicity of
CC       carcinoma cells and may act as a tumor suppressor. Mediates motility of
CC       melanoma cells (By similarity). Required during embryogenesis for
CC       extension of the primary anterior-posterior axis and for outgrowth of
CC       limbs and the genital tubercle (By similarity). Inhibits type II
CC       collagen expression in chondrocytes (PubMed:16754689).
CC       {ECO:0000250|UniProtKB:P22725, ECO:0000250|UniProtKB:P41221,
CC       ECO:0000269|PubMed:16754689}.
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). Homooligomer; disulfide-linked, leading to
CC       inactivation (in vitro). Interacts with PORCN. Interacts with WLS (By
CC       similarity). Interacts with glypican GCP3 (By similarity). Interacts
CC       with PKD1 (via extracellular domain) (By similarity).
CC       {ECO:0000250|UniProtKB:P22725, ECO:0000250|UniProtKB:P41221}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250|UniProtKB:P41221}. Secreted
CC       {ECO:0000269|PubMed:16754689}.
CC   -!- INDUCTION: In cartilage and cultured chondrocytes, induced by
CC       interleukin IL1B. {ECO:0000269|PubMed:16754689}.
CC   -!- PTM: Glycosylation is necessary for secretion but not for activity.
CC       {ECO:0000250|UniProtKB:P22725}.
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   -!- PTM: Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and
CC       formation of large disulfide-bond oligomers, leading to inactivation of
CC       WNT5A. {ECO:0000250|UniProtKB:P22725}.
CC   -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000255}.
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DR   EMBL; DQ388600; ABD47459.1; -; mRNA.
DR   RefSeq; NP_001076134.1; NM_001082665.1.
DR   AlphaFoldDB; Q27Q52; -.
DR   SMR; Q27Q52; -.
DR   STRING; 9986.ENSOCUP00000000333; -.
DR   PRIDE; Q27Q52; -.
DR   Ensembl; ENSOCUT00000000379; ENSOCUP00000000333; ENSOCUG00000000380.
DR   GeneID; 100009381; -.
DR   KEGG; ocu:100009381; -.
DR   CTD; 7474; -.
DR   eggNOG; KOG3913; Eukaryota.
DR   GeneTree; ENSGT00940000158894; -.
DR   InParanoid; Q27Q52; -.
DR   OrthoDB; 695671at2759; -.
DR   Proteomes; UP000001811; Chromosome 9.
DR   Bgee; ENSOCUG00000000380; Expressed in uterus and 15 other tissues.
DR   ExpressionAtlas; Q27Q52; baseline.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0098794; C:postsynapse; IEA:GOC.
DR   GO; GO:1902379; F:chemoattractant activity involved in axon guidance; IEA:Ensembl.
DR   GO; GO:0005125; F:cytokine activity; IEA:Ensembl.
DR   GO; GO:0005109; F:frizzled binding; IEA:Ensembl.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0005115; F:receptor tyrosine kinase-like orphan receptor binding; IEA:Ensembl.
DR   GO; GO:0090630; P:activation of GTPase activity; IEA:Ensembl.
DR   GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR   GO; GO:0008595; P:anterior/posterior axis specification, embryo; IEA:Ensembl.
DR   GO; GO:0003283; P:atrial septum development; IEA:Ensembl.
DR   GO; GO:0048846; P:axon extension involved in axon guidance; IEA:Ensembl.
DR   GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR   GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
DR   GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR   GO; GO:0060067; P:cervix development; IEA:Ensembl.
DR   GO; GO:0036517; P:chemoattraction of serotonergic neuron axon; IEA:Ensembl.
DR   GO; GO:0036518; P:chemorepulsion of dopaminergic neuron axon; IEA:Ensembl.
DR   GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl.
DR   GO; GO:0060028; P:convergent extension involved in axis elongation; IEA:Ensembl.
DR   GO; GO:0060029; P:convergent extension involved in organogenesis; IEA:Ensembl.
DR   GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR   GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR   GO; GO:0010631; P:epithelial cell migration; IEA:Ensembl.
DR   GO; GO:0060750; P:epithelial cell proliferation involved in mammary gland duct elongation; IEA:Ensembl.
DR   GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IEA:Ensembl.
DR   GO; GO:0001736; P:establishment of planar polarity; IEA:Ensembl.
DR   GO; GO:0060324; P:face development; IEA:Ensembl.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR   GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl.
DR   GO; GO:0007442; P:hindgut morphogenesis; IEA:Ensembl.
DR   GO; GO:0048850; P:hypophysis morphogenesis; IEA:Ensembl.
DR   GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR   GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR   GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR   GO; GO:0060599; P:lateral sprouting involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR   GO; GO:0060744; P:mammary gland branching involved in thelarche; IEA:Ensembl.
DR   GO; GO:0140013; P:meiotic nuclear division; IEA:Ensembl.
DR   GO; GO:0097325; P:melanocyte proliferation; IEA:Ensembl.
DR   GO; GO:0010463; P:mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:0060638; P:mesenchymal-epithelial cell signaling; IEA:Ensembl.
DR   GO; GO:0060809; P:mesodermal to mesenchymal transition involved in gastrulation; IEA:Ensembl.
DR   GO; GO:0007494; P:midgut development; IEA:Ensembl.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IEA:Ensembl.
DR   GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR   GO; GO:1904934; P:negative regulation of cell proliferation in midbrain; IEA:Ensembl.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl.
DR   GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0048022; P:negative regulation of melanin biosynthetic process; IEA:Ensembl.
DR   GO; GO:0072201; P:negative regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:0060686; P:negative regulation of prostatic bud formation; IEA:Ensembl.
DR   GO; GO:0051964; P:negative regulation of synapse assembly; IEA:Ensembl.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR   GO; GO:0038031; P:non-canonical Wnt signaling pathway via JNK cascade; IEA:Ensembl.
DR   GO; GO:0048570; P:notochord morphogenesis; IEA:Ensembl.
DR   GO; GO:0021891; P:olfactory bulb interneuron development; IEA:Ensembl.
DR   GO; GO:0048341; P:paraxial mesoderm formation; IEA:Ensembl.
DR   GO; GO:0003402; P:planar cell polarity pathway involved in axis elongation; IEA:Ensembl.
DR   GO; GO:1904938; P:planar cell polarity pathway involved in axon guidance; IEA:Ensembl.
DR   GO; GO:0061350; P:planar cell polarity pathway involved in cardiac muscle tissue morphogenesis; IEA:Ensembl.
DR   GO; GO:0061349; P:planar cell polarity pathway involved in cardiac right atrium morphogenesis; IEA:Ensembl.
DR   GO; GO:0060775; P:planar cell polarity pathway involved in gastrula mediolateral intercalation; IEA:Ensembl.
DR   GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IEA:Ensembl.
DR   GO; GO:0061347; P:planar cell polarity pathway involved in outflow tract morphogenesis; IEA:Ensembl.
DR   GO; GO:0061354; P:planar cell polarity pathway involved in pericardium morphogenesis; IEA:Ensembl.
DR   GO; GO:0061348; P:planar cell polarity pathway involved in ventricular septum morphogenesis; IEA:Ensembl.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR   GO; GO:2000049; P:positive regulation of cell-cell adhesion mediated by cadherin; IEA:Ensembl.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR   GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; IEA:Ensembl.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl.
DR   GO; GO:0090082; P:positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IEA:Ensembl.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; IEA:Ensembl.
DR   GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR   GO; GO:0045836; P:positive regulation of meiotic nuclear division; IEA:Ensembl.
DR   GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR   GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR   GO; GO:0150012; P:positive regulation of neuron projection arborization; IEA:Ensembl.
DR   GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR   GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0045778; P:positive regulation of ossification; IEA:Ensembl.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR   GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Ensembl.
DR   GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR   GO; GO:1900020; P:positive regulation of protein kinase C activity; IEA:Ensembl.
DR   GO; GO:0090037; P:positive regulation of protein kinase C signaling; IEA:Ensembl.
DR   GO; GO:0010820; P:positive regulation of T cell chemotaxis; IEA:Ensembl.
DR   GO; GO:0070245; P:positive regulation of thymocyte apoptotic process; IEA:Ensembl.
DR   GO; GO:0051885; P:positive regulation of timing of anagen; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR   GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IEA:Ensembl.
DR   GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR   GO; GO:0003138; P:primary heart field specification; IEA:Ensembl.
DR   GO; GO:0090009; P:primitive streak formation; IEA:Ensembl.
DR   GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR   GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR   GO; GO:0060762; P:regulation of branching involved in mammary gland duct morphogenesis; IEA:Ensembl.
DR   GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR   GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
DR   GO; GO:0099566; P:regulation of postsynaptic cytosolic calcium ion concentration; IEA:Ensembl.
DR   GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR   GO; GO:0003139; P:secondary heart field specification; IEA:Ensembl.
DR   GO; GO:0062009; P:secondary palate development; IEA:Ensembl.
DR   GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR   GO; GO:0070242; P:thymocyte apoptotic process; IEA:Ensembl.
DR   GO; GO:0003323; P:type B pancreatic cell development; IEA:Ensembl.
DR   GO; GO:0060157; P:urinary bladder development; IEA:Ensembl.
DR   GO; GO:0060065; P:uterus development; IEA:Ensembl.
DR   GO; GO:0060068; P:vagina development; IEA:Ensembl.
DR   GO; GO:1904953; P:Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; IEA:Ensembl.
DR   GO; GO:0007223; P:Wnt signaling pathway, calcium modulating pathway; IEA:Ensembl.
DR   GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR   Gene3D; 3.30.2460.20; -; 1.
DR   InterPro; IPR005817; Wnt.
DR   InterPro; IPR026538; Wnt5a.
DR   InterPro; IPR043158; Wnt_C.
DR   InterPro; IPR018161; Wnt_CS.
DR   PANTHER; PTHR12027; PTHR12027; 1.
DR   PANTHER; PTHR12027:SF33; PTHR12027:SF33; 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   Chondrogenesis; Developmental protein; Differentiation; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Lipoprotein; Reference proteome;
KW   Secreted; Signal; Wnt signaling pathway.
FT   SIGNAL          1..35
FT                   /evidence="ECO:0000255"
FT   PROPEP          36..61
FT                   /evidence="ECO:0000250|UniProtKB:P22725"
FT                   /id="PRO_0000352753"
FT   CHAIN           62..380
FT                   /note="Protein Wnt-5a"
FT                   /evidence="ECO:0000250|UniProtKB:P22725"
FT                   /id="PRO_0000352754"
FT   LIPID           244
FT                   /note="O-palmitoleoyl serine; by PORCN"
FT                   /evidence="ECO:0000250|UniProtKB:P56704"
FT   CARBOHYD        114
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        312
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        326
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        104..115
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        154..162
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        164..182
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        238..252
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        240..247
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        309..340
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        325..335
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        339..379
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        355..370
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        357..367
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        362..363
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
SQ   SEQUENCE   380 AA;  42313 MW;  4EC0F57F69B7D886 CRC64;
     MKKSIGILSP GVALGTAGSA MSSKFFVMAL AVFFSFAQVV IEANSWWSLG MNNPVQMSEV
     YIIGAQPLCS QLAGLSQGQK KLCHLYQDHM QYIGEGAKTG IKECQYQFRH RRWNCSTVDN
     TSVFGRVMQI GSRETAFTYA VSAAGVVNAM SRACREGELS TCGCSRAARP KDLPRDWLWG
     GCGDNIDYGY RFAKEFVDAR ERERIHAKGS YESARILMNL HNNEAGRRTV YNLADVACKC
     HGVSGSCSLK TCWLQLADFR KVGDALKEKY DSAAAMRLNS RGKLVQVNSR FNSPTTQDLV
     YIDPSPDYCV RNESTGSLGT QGRLCNKTSE GMDGCELMCC GRGYDQFKTV QTERCHCKFH
     WCCYVKCKKC TEIVDQFVCK
 
 
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