P28026 (WNT8_XENLA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Wnt-8
Short name=XWnt-8

Gene names

Name:

wnt8

Organism

Xenopus laevis (African clawed frog)

Taxonomic identifier

8355 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amphibia › Batrachia › Anura › Pipoidea › Pipidae › Xenopodinae › Xenopus › Xenopus

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand for members of the frizzled family of seven transmembrane receptors. Plays a role in ventral mesodermal patterning during embryogenesis. Mimics Nieuwkoop center activity. Causes dorsal mesodermal differentiation of animal cap ectoderm when coexpressed with noggin and nuclear, sequence-specific DNA-binding protein xBra. None of these molecules causes dorsal mesoderm formation when expressed alone. Ref.4
Subunit structure	Homooligomer; disulfide-linked, leading to inactivation. Interacts with the long chain of cer1. Ref.5 Ref.6 Ref.7
Subcellular location	Secreted › extracellular space › extracellular matrix.
Developmental stage	Mid-blastula, decline by tailbud.
Post-translational modification	Palmitoylation at Ser-187 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-55. Palmitoylation is necessary for proper trafficking to cell surface By similarity. Ref.7 Proteolytic processing by tiki1 and tiki2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of wnt8.
Sequence similarities	Belongs to the Wnt family.
Sequence caution	The sequence AAA50012.1 differs from that shown. Reason:

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Extracellular matrix Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure
Gene Ontology (GO)
Biological_process	Spemann organizer formation Inferred from mutant phenotype PubMed 9192640. Source: BHF-UCL canonical Wnt receptor signaling pathway involved in neural crest cell differentiation Inferred from mutant phenotype PubMed 18997112. Source: BHF-UCL embryonic axis specification Inferred from mutant phenotype PubMed 12121999. Source: BHF-UCL negative regulation of cardiac cell fate specification Inferred from mutant phenotype PubMed 19862329. Source: BHF-UCL neural crest cell fate commitment Inferred from mutant phenotype PubMed 18997112. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18945944. Source: BHF-UCL regulation of transcription involved in anterior/posterior axis specification Inferred from mutant phenotype PubMed 19623617. Source: BHF-UCL
Cellular_component	proteinaceous extracellular matrix Inferred from direct assay PubMed 19906850. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 358

336

Protein Wnt-8

PRO_0000041447

Sites

Site

39 – 40

2

Cleavage; by tiki1 and tiki2

Site

42 – 43

2

Cleavage; by tiki1 and tiki2

Amino acid modifications

Lipidation

55

1

S-palmitoyl cysteine By similarity

Lipidation

187

1

O-palmitoyl serine Ref.7

Glycosylation

104

1

N-linked (GlcNAc...) Ref.7

Glycosylation

263

1

N-linked (GlcNAc...) Ref.7

Glycosylation

282

1

N-linked (GlcNAc...) Potential

Disulfide bond

55 ↔ 66

Ref.7

Disulfide bond

105 ↔ 113

Ref.7

Disulfide bond

115 ↔ 133

Ref.7

Disulfide bond

181 ↔ 195

Ref.7

Disulfide bond

183 ↔ 190

Ref.7

Disulfide bond

260 ↔ 298

Ref.7

Disulfide bond

276 ↔ 291

Ref.7

Disulfide bond

295 ↔ 337

Ref.7

Disulfide bond

313 ↔ 328

Ref.7

Disulfide bond

315 ↔ 325

Ref.7

Disulfide bond

320 ↔ 321

Ref.7

Experimental info

Sequence conflict

243

1

S → T in AAA50012. Ref.3

Sequence conflict

292

1

K → R in AAA50012. Ref.3

Secondary structure

1

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358

Helix Strand Turn

Details...

Helix

34 – 58

25

Turn

59 – 61

3

Beta strand

62 – 64

3

Helix

72 – 75

4

Helix

84 – 106

23

Turn

107 – 109

3

Turn

118 – 121

4

Beta strand

122 – 125

4

Beta strand

128 – 130

3

Helix

137 – 151

15

Beta strand

154 – 156

3

Helix

157 – 175

19

Beta strand

178 – 183

6

Helix

186 – 188

3

Beta strand

192 – 198

7

Helix

202 – 214

13

Helix

236 – 243

8

Beta strand

247 – 249

3

Beta strand

261 – 263

3

Turn

264 – 267

4

Helix

285 – 288

4

Helix

290 – 294

5

Helix

296 – 298

3

Beta strand

301 – 312

12

Beta strand

319 – 321

3

Beta strand

327 – 338

12

Sequences

	Sequence		Length	Mass (Da)
	P28026 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 8BC8B9E20016E504	FASTA	358	40,176
	10 20 30 40 50 60 MQNTTLFILA TLLIFCPFFT ASAWSVNNFL MTGPKAYLTY SASVAVGAQN GIEECKYQFA 70 80 90 100 110 120 WERWNCPEST LQLATHNGLR SATRETSFVH AISSAGVMYT LTRNCSMGDF DNCGCDDSRN 130 140 150 160 170 180 GRIGGRGWVW GGCSDNAEFG ERISKLFVDG LETGQDARAL MNLHNNEAGR LAVKETMKRT 190 200 210 220 230 240 CKCHGISGSC SIQTCWLQLA EFRDIGNHLK IKHDQALKLE MDKRKMRSGN SADNRGAIAD 250 260 270 280 290 300 AFSSVAGSEL IFLEDSPDYC LKNISLGLQG TEGRECLQSG KNLSQWERRS CKRLCTDCGL 310 320 330 340 350 RVEEKKTEII SSCNCKFHWC CTVKCEQCKQ VVIKHFCARR ERDSNMLNTK RKNRGHRR

References

[1]	"Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis." Christian J.L., McMahon J.A., McMahon A.P., Moon R.T. Development 111:1045-1055(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Neurula.
[2]	"Xwnt-8b: a maternally expressed Xenopus Wnt gene with a potential role in establishing the dorsoventral axis." Cui Y., Brown J.D., Moon R.T., Christian J.L. Development 121:2177-2186(1995) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO C-TERMINUS.
[3]	"Isolation of cDNAs partially encoding four Xenopus Wnt-1/int-1-related proteins and characterization of their transient expression during embryonic development." Christian J.L., Gavin B.J., McMahon A.P., Moon R.T. Dev. Biol. 143:230-234(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 181-321. Tissue: Neurula.
[4]	"Specification of mesodermal pattern in Xenopus laevis by interactions between Brachyury, noggin and Xwnt-8." Cunliffe V., Smith J.C. EMBO J. 13:349-359(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals." Piccolo S., Agius E., Leyns L., Bhattacharyya S., Grunz H., Bouwmeester T., De Robertis E.M. Nature 397:707-710(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CER1.
[6]	"Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation." Zhang X., Abreu J.G., Yokota C., Macdonald B.T., Singh S., Coburn K.L., Cheong S.M., Zhang M.M., Ye Q.Z., Hang H.C., Steen H., He X. Cell 149:1565-1577(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING BY TIKI1 AND TIKI2, SUBUNIT.
[7]	"Structural basis of Wnt recognition by Frizzled." Janda C.Y., Waghray D., Levin A.M., Thomas C., Garcia K.C. Science 337:59-64(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 23-338 IN COMPLEX WITH MOUSE FZD8, GLYCOSYLATION AT ASN-104 AND ASN-263, PALMITOYLATION AT SER-187, DISULFIDE BONDS.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X57234 mRNA. Translation: CAA40510.1.
M55058 mRNA. Translation: AAA50012.1. Sequence problems.

PIR

S18771.

RefSeq

NP_001081637.1. NM_001088168.1.

UniGene

Xl.49.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F0A	X-ray	3.25	B	23-338	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P28026. 1 interaction.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

397970.

KEGG

xla:397970.

Organism-specific databases

CTD

7478.

Xenbase

XB-GENE-866281. wnt8a.

Phylogenomic databases

HOVERGEN

HBG001595.

KO

K00714.

Family and domain databases

InterPro

IPR005817. Wnt.
IPR013301. Wnt8.
IPR018161. Wnt_CS.
[Graphical view]

PANTHER

PTHR12027. PTHR12027. 1 hit.
PTHR12027:SF6. PTHR12027:SF6. 1 hit.

Pfam

PF00110. wnt. 1 hit.
[Graphical view]

PRINTS

PR01892. WNT8PROTEIN.
PR01349. WNTPROTEIN.

SMART

SM00097. WNT1. 1 hit.
[Graphical view]

PROSITE

PS00246. WNT1. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

WNT8_XENLA

Accession

Primary (citable) accession number: P28026

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program