ID   WNT8_XENLA              Reviewed;         358 AA.
AC   P28026;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 128.
DE   RecName: Full=Protein Wnt-8;
DE            Short=XWnt-8;
DE   Flags: Precursor;
GN   Name=wnt8;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Neurula;
RX   PubMed=1879349; DOI=10.1242/dev.111.4.1045;
RA   Christian J.L., McMahon J.A., McMahon A.P., Moon R.T.;
RT   "Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing
RT   growth factors, may play a role in ventral mesodermal patterning during
RT   embryogenesis.";
RL   Development 111:1045-1055(1991).
RN   [2]
RP   SEQUENCE REVISION TO C-TERMINUS.
RX   PubMed=7635061; DOI=10.1242/dev.121.7.2177;
RA   Cui Y., Brown J.D., Moon R.T., Christian J.L.;
RT   "Xwnt-8b: a maternally expressed Xenopus Wnt gene with a potential role in
RT   establishing the dorsoventral axis.";
RL   Development 121:2177-2186(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 181-321.
RC   TISSUE=Neurula;
RX   PubMed=1991549; DOI=10.1016/0012-1606(91)90073-c;
RA   Christian J.L., Gavin B.J., McMahon A.P., Moon R.T.;
RT   "Isolation of cDNAs partially encoding four Xenopus Wnt-1/int-1-related
RT   proteins and characterization of their transient expression during
RT   embryonic development.";
RL   Dev. Biol. 143:230-234(1991).
RN   [4]
RP   FUNCTION.
RX   PubMed=7906224; DOI=10.1002/j.1460-2075.1994.tb06268.x;
RA   Cunliffe V., Smith J.C.;
RT   "Specification of mesodermal pattern in Xenopus laevis by interactions
RT   between Brachyury, noggin and Xwnt-8.";
RL   EMBO J. 13:349-359(1994).
RN   [5]
RP   INTERACTION WITH CER1.
RX   PubMed=10067895; DOI=10.1038/17820;
RA   Piccolo S., Agius E., Leyns L., Bhattacharyya S., Grunz H., Bouwmeester T.,
RA   De Robertis E.M.;
RT   "The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP
RT   and Wnt signals.";
RL   Nature 397:707-710(1999).
RN   [6]
RP   PROTEOLYTIC PROCESSING BY TIKI1 AND TIKI2, AND SUBUNIT.
RX   PubMed=22726442; DOI=10.1016/j.cell.2012.04.039;
RA   Zhang X., Abreu J.G., Yokota C., Macdonald B.T., Singh S., Coburn K.L.,
RA   Cheong S.M., Zhang M.M., Ye Q.Z., Hang H.C., Steen H., He X.;
RT   "Tiki1 is required for head formation via Wnt cleavage-oxidation and
RT   inactivation.";
RL   Cell 149:1565-1577(2012).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 23-338 IN COMPLEX WITH MOUSE
RP   FZD8, GLYCOSYLATION AT ASN-104 AND ASN-263, PALMITOLEOYLATION AT SER-187,
RP   AND DISULFIDE BONDS.
RX   PubMed=22653731; DOI=10.1126/science.1222879;
RA   Janda C.Y., Waghray D., Levin A.M., Thomas C., Garcia K.C.;
RT   "Structural basis of Wnt recognition by Frizzled.";
RL   Science 337:59-64(2012).
CC   -!- FUNCTION: Ligand for members of the frizzled family of seven
CC       transmembrane receptors. Plays a role in ventral mesodermal patterning
CC       during embryogenesis. Mimics Nieuwkoop center activity. Causes dorsal
CC       mesodermal differentiation of animal cap ectoderm when coexpressed with
CC       noggin and nuclear, sequence-specific DNA-binding protein xBra. None of
CC       these molecules causes dorsal mesoderm formation when expressed alone.
CC       {ECO:0000269|PubMed:7906224}.
CC   -!- SUBUNIT: Homooligomer; disulfide-linked, leading to inactivation.
CC       Interacts with the long chain of cer1. {ECO:0000269|PubMed:10067895,
CC       ECO:0000269|PubMed:22653731, ECO:0000269|PubMed:22726442}.
CC   -!- INTERACTION:
CC       P28026; Q6PA07: ptk7.L; NbExp=2; IntAct=EBI-6257743, EBI-7036323;
CC       P28026; Q61091: Fzd8; Xeno; NbExp=3; IntAct=EBI-6257743, EBI-6171689;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix.
CC   -!- DEVELOPMENTAL STAGE: Mid-blastula, decline by tailbud.
CC   -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC       receptors (PubMed:22653731). Depalmitoleoylation leads to Wnt signaling
CC       pathway inhibition (By similarity). {ECO:0000250|UniProtKB:P56704,
CC       ECO:0000269|PubMed:22653731}.
CC   -!- PTM: Proteolytic processing by tiki1 and tiki2 promotes oxidation and
CC       formation of large disulfide-bond oligomers, leading to inactivation of
CC       wnt8. {ECO:0000269|PubMed:22726442}.
CC   -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA50012.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR   EMBL; X57234; CAA40510.1; -; mRNA.
DR   EMBL; M55058; AAA50012.1; ALT_SEQ; mRNA.
DR   PIR; S18771; S18771.
DR   RefSeq; NP_001081637.1; NM_001088168.1.
DR   PDB; 4F0A; X-ray; 3.25 A; B=23-338.
DR   PDB; 8CTG; EM; 3.80 A; B=22-329.
DR   PDBsum; 4F0A; -.
DR   PDBsum; 8CTG; -.
DR   AlphaFoldDB; P28026; -.
DR   EMDB; EMD-26989; -.
DR   SMR; P28026; -.
DR   BioGRID; 99305; 1.
DR   IntAct; P28026; 3.
DR   MINT; P28026; -.
DR   GlyCosmos; P28026; 3 sites, No reported glycans.
DR   iPTMnet; P28026; -.
DR   DNASU; 397970; -.
DR   GeneID; 397970; -.
DR   KEGG; xla:397970; -.
DR   AGR; Xenbase:XB-GENE-866281; -.
DR   CTD; 397970; -.
DR   Xenbase; XB-GENE-866281; wnt8a.L.
DR   OrthoDB; 2874082at2759; -.
DR   Proteomes; UP000186698; Chromosome 3L.
DR   Bgee; 397970; Expressed in gastrula and 3 other cell types or tissues.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005109; F:frizzled binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0002020; F:protease binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0009948; P:anterior/posterior axis specification; IMP:BHF-UCL.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0000578; P:embryonic axis specification; IMP:BHF-UCL.
DR   GO; GO:2000044; P:negative regulation of cardiac cell fate specification; IMP:BHF-UCL.
DR   GO; GO:0014034; P:neural crest cell fate commitment; IMP:BHF-UCL.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0060061; P:Spemann organizer formation; IMP:BHF-UCL.
DR   GO; GO:0016055; P:Wnt signaling pathway; IDA:BHF-UCL.
DR   CDD; cd19351; Wnt_Wnt8a; 1.
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:SF92; PROTEIN WNT-8A; 1.
DR   PANTHER; PTHR12027; WNT RELATED; 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; Developmental protein; Disulfide bond; Extracellular matrix;
KW   Glycoprotein; Lipoprotein; Reference proteome; Secreted; Signal;
KW   Wnt signaling pathway.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..358
FT                   /note="Protein Wnt-8"
FT                   /id="PRO_0000041447"
FT   SITE            39..40
FT                   /note="Cleavage; by tiki1 and tiki2"
FT                   /evidence="ECO:0000269|PubMed:22726442"
FT   SITE            42..43
FT                   /note="Cleavage; by tiki1 and tiki2"
FT                   /evidence="ECO:0000269|PubMed:22726442"
FT   LIPID           187
FT                   /note="O-palmitoleoyl serine"
FT                   /evidence="ECO:0000269|PubMed:22653731"
FT   CARBOHYD        104
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        55..66
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        105..113
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        115..133
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        181..195
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        183..190
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        260..298
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        276..291
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        295..337
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        313..328
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        315..325
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   DISULFID        320..321
FT                   /evidence="ECO:0000269|PubMed:22653731,
FT                   ECO:0007744|PDB:4F0A"
FT   CONFLICT        243
FT                   /note="S -> T (in Ref. 3; AAA50012)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        292
FT                   /note="K -> R (in Ref. 3; AAA50012)"
FT                   /evidence="ECO:0000305"
FT   HELIX           34..58
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   TURN            59..61
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          62..64
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           72..75
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           84..106
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   TURN            107..109
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   TURN            118..121
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          122..125
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          128..130
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           137..151
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          154..156
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           157..175
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          178..183
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           186..188
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          192..198
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           202..214
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           236..243
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          247..249
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          261..263
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   TURN            264..267
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           285..288
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           290..294
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   HELIX           296..298
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          301..312
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          319..321
FT                   /evidence="ECO:0007829|PDB:4F0A"
FT   STRAND          327..338
FT                   /evidence="ECO:0007829|PDB:4F0A"
SQ   SEQUENCE   358 AA;  40176 MW;  8BC8B9E20016E504 CRC64;
     MQNTTLFILA TLLIFCPFFT ASAWSVNNFL MTGPKAYLTY SASVAVGAQN GIEECKYQFA
     WERWNCPEST LQLATHNGLR SATRETSFVH AISSAGVMYT LTRNCSMGDF DNCGCDDSRN
     GRIGGRGWVW GGCSDNAEFG ERISKLFVDG LETGQDARAL MNLHNNEAGR LAVKETMKRT
     CKCHGISGSC SIQTCWLQLA EFRDIGNHLK IKHDQALKLE MDKRKMRSGN SADNRGAIAD
     AFSSVAGSEL IFLEDSPDYC LKNISLGLQG TEGRECLQSG KNLSQWERRS CKRLCTDCGL
     RVEEKKTEII SSCNCKFHWC CTVKCEQCKQ VVIKHFCARR ERDSNMLNTK RKNRGHRR
//