WNT8_XENLA
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 03-AUG-2022, entry version 121.
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 PDBsum; 4F0A; -.
DR AlphaFoldDB; P28026; -.
DR SMR; P28026; -.
DR BioGRID; 99305; 1.
DR IntAct; P28026; 3.
DR MINT; P28026; -.
DR iPTMnet; P28026; -.
DR DNASU; 397970; -.
DR GeneID; 397970; -.
DR KEGG; xla:397970; -.
DR CTD; 397970; -.
DR Xenbase; XB-GENE-866281; wnt8a.L.
DR OrthoDB; 618621at2759; -.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 397970; Expressed in gastrula and 3 other 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:0044335; P:canonical Wnt signaling pathway involved in neural crest cell differentiation; IMP: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 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; 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
