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Protein

Protein Wnt-10b

Gene

WNT10B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-catenin/LEF/TCF-mediated transcriptional programs. Involved in signaling networks controlling stemness, pluripotency and cell fate decisions. Acts in the immune system, mammary gland, adipose tissue, bone and skin.3 Publications

GO - Molecular functioni

  • frizzled binding Source: GO_Central
  • receptor agonist activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-3238698. WNT ligand biogenesis and trafficking.
R-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiO00744.
SIGNORiO00744.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Wnt-10b
Alternative name(s):
Protein Wnt-12
Gene namesi
Name:WNT10B
Synonyms:WNT12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000169884.13.
HGNCiHGNC:12775. WNT10B.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Split-hand/foot malformation 6 (SHFM6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.
See also OMIM:225300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062516332R → W in SHFM6. 1 PublicationCorresponds to variant dbSNP:rs121918349Ensembl.1
Tooth agenesis, selective, 8 (STHAG8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. Potential genotype-phenotype correlation between variants and the positions of missing teeth.1 Publication
Disease descriptionA form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG8 inheritance is autosomal dominant.
See also OMIM:617073
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076926211R → Q in STHAG8; reduced activation of Wnt signaling; reduced endothelial differentiation. 1 PublicationCorresponds to variant dbSNP:rs779326570Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7480.
MalaCardsiWNT10B.
MIMi225300. phenotype.
617073. phenotype.
OpenTargetsiENSG00000169884.
Orphaneti2440. Split hand-split foot malformation.
PharmGKBiPA37377.

Polymorphism and mutation databases

BioMutaiWNT10B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000004146329 – 389Protein Wnt-10bAdd BLAST361

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46PhosphothreonineCombined sources1
Disulfide bondi83 ↔ 94By similarity
Glycosylationi93N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi136 ↔ 144By similarity
Disulfide bondi146 ↔ 199By similarity
Disulfide bondi247 ↔ 261By similarity
Disulfide bondi249 ↔ 256By similarity
Lipidationi253O-palmitoleyl serine; by PORCNBy similarity1
Disulfide bondi334 ↔ 349By similarity
Glycosylationi335N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi364 ↔ 379By similarity
Disulfide bondi366 ↔ 376By similarity
Disulfide bondi371 ↔ 372By similarity

Post-translational modificationi

Palmitoleylation is required for efficient binding to frizzled receptors. Depalmitoleylation leads to Wnt signaling pathway inhibition.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Phosphoprotein

Proteomic databases

EPDiO00744.
PaxDbiO00744.
PeptideAtlasiO00744.
PRIDEiO00744.

PTM databases

iPTMnetiO00744.
PhosphoSitePlusiO00744.

Expressioni

Tissue specificityi

Detected in most adult tissues. Highest levels were found in heart and skeletal muscle. Low levels are found in brain.

Developmental stagei

Infant brain has higher levels of WNT10B than adult brain.

Gene expression databases

BgeeiENSG00000169884.
CleanExiHS_WNT10B.
ExpressionAtlasiO00744. baseline and differential.
GenevisibleiO00744. HS.

Organism-specific databases

HPAiHPA055048.
HPA062539.

Interactioni

GO - Molecular functioni

  • frizzled binding Source: GO_Central
  • receptor agonist activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi113317. 6 interactors.
STRINGi9606.ENSP00000301061.

Structurei

3D structure databases

ProteinModelPortaliO00744.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913. Eukaryota.
ENOG410XQZ1. LUCA.
GeneTreeiENSGT00760000118943.
HOGENOMiHOG000039528.
HOVERGENiHBG001595.
InParanoidiO00744.
KOiK01357.
OMAiQIVTDNM.
OrthoDBiEOG091G0OFF.
PhylomeDBiO00744.
TreeFamiTF105310.

Family and domain databases

InterProiView protein in InterPro
IPR005817. Wnt.
IPR013302. Wnt10.
IPR018161. Wnt_CS.
PANTHERiPTHR12027. PTHR12027. 1 hit.
PfamiView protein in Pfam
PF00110. wnt. 1 hit.
PRINTSiPR01893. WNT10PROTEIN.
PR01349. WNTPROTEIN.
SMARTiView protein in SMART
SM00097. WNT1. 1 hit.
PROSITEiView protein in PROSITE
PS00246. WNT1. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00744-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLEEPRPRPP PSGLAGLLFL ALCSRALSNE ILGLKLPGEP PLTANTVCLT
60 70 80 90 100
LSGLSKRQLG LCLRNPDVTA SALQGLHIAV HECQHQLRDQ RWNCSALEGG
110 120 130 140 150
GRLPHHSAIL KRGFRESAFS FSMLAAGVMH AVATACSLGK LVSCGCGWKG
160 170 180 190 200
SGEQDRLRAK LLQLQALSRG KSFPHSLPSP GPGSSPSPGP QDTWEWGGCN
210 220 230 240 250
HDMDFGEKFS RDFLDSREAP RDIQARMRIH NNRVGRQVVT ENLKRKCKCH
260 270 280 290 300
GTSGSCQFKT CWRAAPEFRA VGAALRERLG RAIFIDTHNR NSGAFQPRLR
310 320 330 340 350
PRRLSGELVY FEKSPDFCER DPTMGSPGTR GRACNKTSRL LDGCGSLCCG
360 370 380
RGHNVLRQTR VERCHCRFHW CCYVLCDECK VTEWVNVCK
Length:389
Mass (Da):43,000
Last modified:May 10, 2002 - v2
Checksum:iF973F2CA0DB115EF
GO
Isoform 2 (identifier: O00744-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     172-191: SFPHSLPSPGPGSSPSPGPQ → LPGTSRHECESTTTGWGARW
     192-389: Missing.

Note: No experimental confirmation available.
Show »
Length:191
Mass (Da):20,483
Checksum:i07A9A02483680C55
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60G → D in AAB51685 (PubMed:9284937).Curated1
Sequence conflicti149K → R in CAA65769 (PubMed:9121776).Curated1
Sequence conflicti295F → S in CAA65769 (PubMed:9121776).Curated1
Sequence conflicti311F → L in CAA65769 (PubMed:9121776).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06251277H → Y1 PublicationCorresponds to variant dbSNP:rs151284263Ensembl.1
Natural variantiVAR_076926211R → Q in STHAG8; reduced activation of Wnt signaling; reduced endothelial differentiation. 1 PublicationCorresponds to variant dbSNP:rs779326570Ensembl.1
Natural variantiVAR_062513256C → Y Associated with obesity; abrogates the ability of WNT10B to activate canonical Wnt signaling and blocks adipogenesis. 1 Publication1
Natural variantiVAR_062514285I → T1 PublicationCorresponds to variant dbSNP:rs146010731Ensembl.1
Natural variantiVAR_062515301P → S1 PublicationCorresponds to variant dbSNP:rs35034312Ensembl.1
Natural variantiVAR_062516332R → W in SHFM6. 1 PublicationCorresponds to variant dbSNP:rs121918349Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056289172 – 191SFPHS…SPGPQ → LPGTSRHECESTTTGWGARW in isoform 2. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_056290192 – 389Missing in isoform 2. 1 PublicationAdd BLAST198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81787 mRNA. Translation: AAB51685.1.
AB070724 mRNA. Translation: BAB72181.1.
AK312906 mRNA. Translation: BAG35752.1.
AC073610 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58028.1.
BC096353 mRNA. Translation: AAH96353.1.
BC096354 mRNA. Translation: AAH96354.1.
BC096355 mRNA. Translation: AAH96355.1.
BC096356 mRNA. Translation: AAH96356.1.
X97057 mRNA. Translation: CAA65769.1.
AF028700 Genomic DNA. Translation: AAC39549.1.
CCDSiCCDS8775.1. [O00744-1]
RefSeqiNP_003385.2. NM_003394.3. [O00744-1]
UniGeneiHs.91985.

Genome annotation databases

EnsembliENST00000301061; ENSP00000301061; ENSG00000169884. [O00744-1]
ENST00000407467; ENSP00000384691; ENSG00000169884. [O00744-2]
GeneIDi7480.
KEGGihsa:7480.
UCSCiuc001rss.4. human. [O00744-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiWN10B_HUMAN
AccessioniPrimary (citable) accession number: O00744
Secondary accession number(s): B2R7A5
, O00747, Q4VAJ4, Q4VAJ5, Q8WZ97
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 10, 2002
Last modified: September 27, 2017
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families