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UniProtKB - P04628 (WNT1_HUMAN)

Protein

Proto-oncogene Wnt-1

Gene

WNT1

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

Functioni

Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (PubMed:23499309, PubMed:26902720, PubMed:28528193, PubMed:23656646). In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling (By similarity). Plays an essential role in the development of the embryonic brain and central nervous system (CNS) (By similarity). Has a role in osteoblast function, bone development and bone homeostasis (PubMed:23499309, PubMed:23656646).By similarityCurated4 Publications

Caution

A palmitoylation site was proposed at Cys-93, but it was later shown that this cysteine is engaged in a disulfide bond.1 Publication

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • frizzled binding Source: GO_Central
  • morphogen activity Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: Ensembl
  • receptor ligand activity Source: WormBase
  • transcription regulatory region DNA binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-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
R-HSA-4086400 PCP/CE pathway
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
SignaLinkiP04628
SIGNORiP04628

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene Wnt-1
Alternative name(s):
Proto-oncogene Int-1 homolog
Gene namesi
Name:WNT1
Synonyms:INT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000125084.11
HGNCiHGNC:12774 WNT1
MIMi164820 gene
neXtProtiNX_P04628

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

Osteoporosis (OSTEOP)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs.
See also OMIM:166710
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069629218C → G in OSTEOP; reduced capacity to activate canonical Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397514702EnsemblClinVar.1
Natural variantiVAR_069630235R → W in OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 PublicationCorresponds to variant dbSNP:rs387907359EnsemblClinVar.1
Osteogenesis imperfecta 15 (OI15)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.
See also OMIM:615220
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079407123E → D in OI15; detected in a compound heterozygote also carrying G-153; reduced capacity to activate canonical Wnt signaling. 1 Publication1
Natural variantiVAR_069627143C → F in OI15. 1 Publication1
Natural variantiVAR_079408153C → G in OI15; detected in a compound heterozygote also carrying D-123; reduced capacity to activate canonical Wnt signaling. 1 Publication1
Natural variantiVAR_069628177G → C in OI15; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 Publication1
Natural variantiVAR_069631298F → C in OI15. 2 Publications1
Natural variantiVAR_069632355V → F in OI15. 1 PublicationCorresponds to variant dbSNP:rs387907358EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta, Proto-oncogene

Organism-specific databases

DisGeNETi7471
MalaCardsiWNT1
MIMi166710 phenotype
615220 phenotype
615221 phenotype
OpenTargetsiENSG00000125084
Orphaneti85193 Idiopathic juvenile osteoporosis
216812 Osteogenesis imperfecta type 3
216820 Osteogenesis imperfecta type 4
PharmGKBiPA37376

Polymorphism and mutation databases

BioMutaiWNT1
DMDMi139743

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000004140528 – 370Proto-oncogene Wnt-1Add BLAST343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi29N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi93 ↔ 104By similarity
Disulfide bondi143 ↔ 151By similarity
Disulfide bondi153 ↔ 170By similarity
Disulfide bondi218 ↔ 232By similarity
Disulfide bondi220 ↔ 227By similarity
Lipidationi224O-palmitoleoyl serine; by PORCNBy similarity1
Disulfide bondi315 ↔ 330By similarity
Glycosylationi316N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi345 ↔ 360By similarity
Glycosylationi346N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi347 ↔ 357By similarity
Disulfide bondi352 ↔ 353By similarity
Glycosylationi359N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (Probable). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity).By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

PaxDbiP04628
PeptideAtlasiP04628
PRIDEiP04628
ProteomicsDBi51722

PTM databases

iPTMnetiP04628
PhosphoSitePlusiP04628
SwissPalmiP04628

Expressioni

Gene expression databases

BgeeiENSG00000125084 Expressed in 40 organ(s), highest expression level in nucleus accumbens
CleanExiHS_WNT1
ExpressionAtlasiP04628 baseline and differential
GenevisibleiP04628 HS

Interactioni

Subunit structurei

Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3 (By similarity). Interacts with WLS (By similarity).By similarity1 Publication

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi113308, 9 interactors
STRINGi9606.ENSP00000293549

Structurei

3D structure databases

ProteinModelPortaliP04628
SMRiP04628
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOGENOMiHOG000039528
HOVERGENiHBG001595
InParanoidiP04628
KOiK03209
OMAiWNCPTAS
OrthoDBiEOG091G0OFF
PhylomeDBiP04628
TreeFamiTF105310

Family and domain databases

InterProiView protein in InterPro
IPR005817 Wnt
IPR009139 Wnt1
IPR018161 Wnt_CS
PANTHERiPTHR12027 PTHR12027, 2 hits
PfamiView protein in Pfam
PF00110 wnt, 1 hit
PRINTSiPR01841 WNT1PROTEIN
PR01349 WNTPROTEIN
SMARTiView protein in SMART
SM00097 WNT1, 1 hit
PROSITEiView protein in PROSITE
PS00246 WNT1, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P04628-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGLWALLPGW VSATLLLALA ALPAALAANS SGRWWGIVNV ASSTNLLTDS 
        60         70         80         90        100
KSLQLVLEPS LQLLSRKQRR LIRQNPGILH SVSGGLQSAV RECKWQFRNR 
       110        120        130        140        150
RWNCPTAPGP HLFGKIVNRG CRETAFIFAI TSAGVTHSVA RSCSEGSIES 
       160        170        180        190        200
CTCDYRRRGP GGPDWHWGGC SDNIDFGRLF GREFVDSGEK GRDLRFLMNL 
       210        220        230        240        250
HNNEAGRTTV FSEMRQECKC HGMSGSCTVR TCWMRLPTLR AVGDVLRDRF 
       260        270        280        290        300
DGASRVLYGN RGSNRASRAE LLRLEPEDPA HKPPSPHDLV YFEKSPNFCT 
       310        320        330        340        350
YSGRLGTAGT AGRACNSSSP ALDGCELLCC GRGHRTRTQR VTERCNCTFH 
       360        370
WCCHVSCRNC THTRVLHECL
Length:370
Mass (Da):40,982
Last modified:August 13, 1987 - v1
Checksum:iF7E8111DA12E173F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WXR9A0A087WXR9_HUMAN
Protein Wnt
WNT1
359Annotation score:

Polymorphismi

Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIMi:615221]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079407123E → D in OI15; detected in a compound heterozygote also carrying G-153; reduced capacity to activate canonical Wnt signaling. 1 Publication1
Natural variantiVAR_069627143C → F in OI15. 1 Publication1
Natural variantiVAR_079408153C → G in OI15; detected in a compound heterozygote also carrying D-123; reduced capacity to activate canonical Wnt signaling. 1 Publication1
Natural variantiVAR_069628177G → C in OI15; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 Publication1
Natural variantiVAR_069629218C → G in OSTEOP; reduced capacity to activate canonical Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397514702EnsemblClinVar.1
Natural variantiVAR_069630235R → W in OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 PublicationCorresponds to variant dbSNP:rs387907359EnsemblClinVar.1
Natural variantiVAR_069631298F → C in OI15. 2 Publications1
Natural variantiVAR_069632355V → F in OI15. 1 PublicationCorresponds to variant dbSNP:rs387907358EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03072 Genomic DNA Translation: CAA26874.1
BT019429 mRNA Translation: AAV38236.1
CH471111 Genomic DNA Translation: EAW58030.1
BC074798 mRNA Translation: AAH74798.1
BC074799 mRNA Translation: AAH74799.1
CCDSiCCDS8776.1
PIRiA24674 TVHUT1
RefSeqiNP_005421.1, NM_005430.3
UniGeneiHs.248164

Genome annotation databases

EnsembliENST00000293549; ENSP00000293549; ENSG00000125084
GeneIDi7471
KEGGihsa:7471
UCSCiuc001rsu.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03072 Genomic DNA Translation: CAA26874.1
BT019429 mRNA Translation: AAV38236.1
CH471111 Genomic DNA Translation: EAW58030.1
BC074798 mRNA Translation: AAH74798.1
BC074799 mRNA Translation: AAH74799.1
CCDSiCCDS8776.1
PIRiA24674 TVHUT1
RefSeqiNP_005421.1, NM_005430.3
UniGeneiHs.248164

3D structure databases

ProteinModelPortaliP04628
SMRiP04628
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113308, 9 interactors
STRINGi9606.ENSP00000293549

PTM databases

iPTMnetiP04628
PhosphoSitePlusiP04628
SwissPalmiP04628

Polymorphism and mutation databases

BioMutaiWNT1
DMDMi139743

Proteomic databases

PaxDbiP04628
PeptideAtlasiP04628
PRIDEiP04628
ProteomicsDBi51722

Protocols and materials databases

DNASUi7471
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293549; ENSP00000293549; ENSG00000125084
GeneIDi7471
KEGGihsa:7471
UCSCiuc001rsu.4 human

Organism-specific databases

CTDi7471
DisGeNETi7471
EuPathDBiHostDB:ENSG00000125084.11
GeneCardsiWNT1
HGNCiHGNC:12774 WNT1
MalaCardsiWNT1
MIMi164820 gene
166710 phenotype
615220 phenotype
615221 phenotype
neXtProtiNX_P04628
OpenTargetsiENSG00000125084
Orphaneti85193 Idiopathic juvenile osteoporosis
216812 Osteogenesis imperfecta type 3
216820 Osteogenesis imperfecta type 4
PharmGKBiPA37376
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOGENOMiHOG000039528
HOVERGENiHBG001595
InParanoidiP04628
KOiK03209
OMAiWNCPTAS
OrthoDBiEOG091G0OFF
PhylomeDBiP04628
TreeFamiTF105310

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-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
R-HSA-4086400 PCP/CE pathway
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
SignaLinkiP04628
SIGNORiP04628

Miscellaneous databases

GeneWikiiWNT1
GenomeRNAii7471
PROiPR:P04628
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125084 Expressed in 40 organ(s), highest expression level in nucleus accumbens
CleanExiHS_WNT1
ExpressionAtlasiP04628 baseline and differential
GenevisibleiP04628 HS

Family and domain databases

InterProiView protein in InterPro
IPR005817 Wnt
IPR009139 Wnt1
IPR018161 Wnt_CS
PANTHERiPTHR12027 PTHR12027, 2 hits
PfamiView protein in Pfam
PF00110 wnt, 1 hit
PRINTSiPR01841 WNT1PROTEIN
PR01349 WNTPROTEIN
SMARTiView protein in SMART
SM00097 WNT1, 1 hit
PROSITEiView protein in PROSITE
PS00246 WNT1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiWNT1_HUMAN
AccessioniPrimary (citable) accession number: P04628
Secondary accession number(s): Q5U0N2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: November 7, 2018
This is version 176 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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