WNT8A_HUMAN
ID WNT8A_HUMAN Reviewed; 351 AA.
AC Q9H1J5; Q96S51;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Protein Wnt-8a;
DE AltName: Full=Protein Wnt-8d;
DE Flags: Precursor;
GN Name=WNT8A; Synonyms=WNT8D;
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] (ISOFORM 1).
RX PubMed=11408932;
RA Saitoh T., Katoh M.;
RT "Molecular cloning and characterization of human WNT8A.";
RL Int. J. Oncol. 19:123-127(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Testa T.T., Mossakowska D.E., Carter P.S., Hu E., Zhu Y., Kelsell D.P.,
RA Murdock P.R., Herrity N.C., Lewis C.J., Cross D.A., Culbert A.A.,
RA Reith A.D., Barnes M.R.;
RT "Molecular cloning and characterization of six novel human WNT genes.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
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. Plays a role in embryonic patterning.
CC {ECO:0000250|UniProtKB:P51028}.
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).
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305}. Secreted {ECO:0000269|PubMed:26902720}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H1J5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H1J5-2; Sequence=VSP_038706;
CC -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC receptors (By similarity). Depalmitoleoylation leads to Wnt signaling
CC pathway inhibition (By similarity). {ECO:0000250|UniProtKB:P28026,
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 WNT8A. {ECO:0000250|UniProtKB:P28026}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
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DR EMBL; AB057725; BAB60960.1; -; mRNA.
DR EMBL; AY009402; AAG38662.1; -; mRNA.
DR CCDS; CCDS43368.1; -. [Q9H1J5-1]
DR RefSeq; NP_001287867.1; NM_001300938.1.
DR RefSeq; NP_001287868.1; NM_001300939.1.
DR RefSeq; NP_490645.1; NM_058244.3. [Q9H1J5-1]
DR PDB; 7KC4; EM; 3.19 A; D=1-351.
DR PDBsum; 7KC4; -.
DR AlphaFoldDB; Q9H1J5; -.
DR SMR; Q9H1J5; -.
DR BioGRID; 113315; 28.
DR IntAct; Q9H1J5; 3.
DR STRING; 9606.ENSP00000426653; -.
DR GlyGen; Q9H1J5; 3 sites.
DR iPTMnet; Q9H1J5; -.
DR PhosphoSitePlus; Q9H1J5; -.
DR BioMuta; WNT8A; -.
DR DMDM; 288558833; -.
DR REPRODUCTION-2DPAGE; Q9H1J5; -.
DR jPOST; Q9H1J5; -.
DR MassIVE; Q9H1J5; -.
DR PaxDb; Q9H1J5; -.
DR PeptideAtlas; Q9H1J5; -.
DR PRIDE; Q9H1J5; -.
DR ProteomicsDB; 80418; -. [Q9H1J5-1]
DR ProteomicsDB; 80419; -. [Q9H1J5-2]
DR Antibodypedia; 26566; 226 antibodies from 31 providers.
DR DNASU; 7478; -.
DR Ensembl; ENST00000361560.6; ENSP00000354726.2; ENSG00000061492.12. [Q9H1J5-2]
DR Ensembl; ENST00000398754.1; ENSP00000381739.1; ENSG00000061492.12. [Q9H1J5-1]
DR GeneID; 7478; -.
DR KEGG; hsa:7478; -.
DR UCSC; uc003lcd.1; human. [Q9H1J5-1]
DR CTD; 7478; -.
DR DisGeNET; 7478; -.
DR GeneCards; WNT8A; -.
DR HGNC; HGNC:12788; WNT8A.
DR HPA; ENSG00000061492; Not detected.
DR MIM; 606360; gene.
DR neXtProt; NX_Q9H1J5; -.
DR OpenTargets; ENSG00000061492; -.
DR PharmGKB; PA37389; -.
DR VEuPathDB; HostDB:ENSG00000061492; -.
DR eggNOG; KOG3913; Eukaryota.
DR GeneTree; ENSGT00940000157840; -.
DR HOGENOM; CLU_033039_1_2_1; -.
DR InParanoid; Q9H1J5; -.
DR OrthoDB; 618621at2759; -.
DR PhylomeDB; Q9H1J5; -.
DR TreeFam; TF105310; -.
DR PathwayCommons; Q9H1J5; -.
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-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR SignaLink; Q9H1J5; -.
DR SIGNOR; Q9H1J5; -.
DR BioGRID-ORCS; 7478; 6 hits in 1063 CRISPR screens.
DR GenomeRNAi; 7478; -.
DR Pharos; Q9H1J5; Tbio.
DR PRO; PR:Q9H1J5; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H1J5; protein.
DR Bgee; ENSG00000061492; Expressed in nucleus accumbens and 20 other tissues.
DR ExpressionAtlas; Q9H1J5; baseline and differential.
DR Genevisible; Q9H1J5; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:BHF-UCL.
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:0009948; P:anterior/posterior axis specification; ISS:ARUK-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:WormBase.
DR GO; GO:0061317; P:canonical Wnt signaling pathway involved in cardiac muscle cell fate commitment; IEP:BHF-UCL.
DR GO; GO:0044335; P:canonical Wnt signaling pathway involved in neural crest cell differentiation; ISS:BHF-UCL.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0014034; P:neural crest cell fate commitment; ISS:BHF-UCL.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0032526; P:response to retinoic acid; NAS:BHF-UCL.
DR GO; GO:0062009; P:secondary palate development; IMP:BHF-UCL.
DR Gene3D; 3.30.2460.20; -; 1.
DR InterPro; IPR034312; Protein_Wnt-8A/8C.
DR InterPro; IPR005817; Wnt.
DR InterPro; IPR013301; Wnt8.
DR InterPro; IPR043158; Wnt_C.
DR InterPro; IPR018161; Wnt_CS.
DR PANTHER; PTHR12027; PTHR12027; 1.
DR PANTHER; PTHR12027:SF92; PTHR12027:SF92; 1.
DR Pfam; PF00110; wnt; 1.
DR PRINTS; PR01892; WNT8PROTEIN.
DR PRINTS; PR01349; WNTPROTEIN.
DR SMART; SM00097; WNT1; 1.
DR PROSITE; PS00246; WNT1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Developmental protein; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Lipoprotein; Reference proteome;
KW Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..351
FT /note="Protein Wnt-8a"
FT /id="PRO_0000041448"
FT LIPID 186
FT /note="O-palmitoleoyl serine"
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..65
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 104..112
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 114..132
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 180..194
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 182..189
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 259..297
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 275..290
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 294..336
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 312..327
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 314..324
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT DISULFID 319..320
FT /evidence="ECO:0000250|UniProtKB:P28026"
FT VAR_SEQ 348..351
FT /note="KGSA -> RVWFGVYI (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038706"
FT HELIX 25..30
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 40..57
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 83..105
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 127..130
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 137..148
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 156..175
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:7KC4"
FT HELIX 201..213
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 263..266
FT /evidence="ECO:0007829|PDB:7KC4"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:7KC4"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:7KC4"
SQ SEQUENCE 351 AA; 38849 MW; B3432171301C17E5 CRC64;
MGNLFMLWAA LGICCAAFSA SAWSVNNFLI TGPKAYLTYT TSVALGAQSG IEECKFQFAW
ERWNCPENAL QLSTHNRLRS ATRETSFIHA ISSAGVMYII TKNCSMGDFE NCGCDGSNNG
KTGGHGWIWG GCSDNVEFGE RISKLFVDSL EKGKDARALM NLHNNRAGRL AVRATMKRTC
KCHGISGSCS IQTCWLQLAE FREMGDYLKA KYDQALKIEM DKRQLRAGNS AEGHWVPAEA
FLPSAEAELI FLEESPDYCT CNSSLGIYGT EGRECLQNSH NTSRWERRSC GRLCTECGLQ
VEERKTEVIS SCNCKFQWCC TVKCDQCRHV VSKYYCARSP GSAQSLGKGS A
