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Protein

Proto-oncogene Wnt-1

Gene

WNT1

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

Functioni

Ligand for members of the frizzled family of seven transmembrane receptors. In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling. Probable developmental protein. May be a signaling molecule important in CNS development. Is likely to signal over only few cell diameters. Has a role in osteoblast function and bone development.1 Publication

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • frizzled binding Source: ParkinsonsUK-UCL
  • morphogen activity Source: ParkinsonsUK-UCL
  • receptor agonist activity Source: ParkinsonsUK-UCL
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:12774. WNT1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti218 – 2181C → G in OSTEOP; reduced capacity to activate canonical WNT signaling. 1 Publication
Corresponds to variant rs397514702 [ dbSNP | Ensembl ].
VAR_069629
Natural varianti235 – 2351R → W in OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the WNT-regulated beta-catenin signaling cascade. 1 Publication
Corresponds to variant rs387907359 [ dbSNP | Ensembl ].
VAR_069630
Osteogenesis imperfecta 15 (OI15)4 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431C → F in OI15. 1 Publication
VAR_069627
Natural varianti177 – 1771G → C in OI15; completely fails to activate the WNT-regulated beta-catenin signaling cascade. 1 Publication
VAR_069628
Natural varianti298 – 2981F → C in OI15. 2 Publications
VAR_069631
Natural varianti355 – 3551V → F in OI15. 1 Publication
Corresponds to variant rs387907358 [ dbSNP | Ensembl ].
VAR_069632

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta, Proto-oncogene

Organism-specific databases

MalaCardsiWNT1.
MIMi166710. phenotype.
615220. phenotype.
615221. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 370343Proto-oncogene Wnt-1PRO_0000041405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi29 – 291N-linked (GlcNAc...)Sequence analysis
Disulfide bondi93 ↔ 104By similarity
Disulfide bondi143 ↔ 151By similarity
Disulfide bondi153 ↔ 170By similarity
Disulfide bondi218 ↔ 232By similarity
Disulfide bondi220 ↔ 227By similarity
Lipidationi224 – 2241O-palmitoleyl serine; by PORCNBy similarity
Disulfide bondi315 ↔ 330By similarity
Glycosylationi316 – 3161N-linked (GlcNAc...)Sequence analysis
Disulfide bondi345 ↔ 360By similarity
Glycosylationi346 – 3461N-linked (GlcNAc...)Sequence analysis
Disulfide bondi347 ↔ 357By similarity
Disulfide bondi352 ↔ 353By similarity
Glycosylationi359 – 3591N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

PaxDbiP04628.
PRIDEiP04628.

PTM databases

iPTMnetiP04628.
PhosphoSiteiP04628.
SwissPalmiP04628.

Expressioni

Gene expression databases

BgeeiENSG00000125084.
CleanExiHS_WNT1.
ExpressionAtlasiP04628. baseline and differential.
GenevisibleiP04628. HS.

Organism-specific databases

HPAiCAB025366.

Interactioni

Subunit structurei

Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3 (By similarity). Interacts with WLS (By similarity).By similarity

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • frizzled binding Source: ParkinsonsUK-UCL
  • receptor agonist activity Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi113308. 7 interactions.
STRINGi9606.ENSP00000293549.

Structurei

3D structure databases

ProteinModelPortaliP04628.
SMRiP04628. Positions 85-299.
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.
OMAiNNSGRWW.
OrthoDBiEOG091G0OFF.
PhylomeDBiP04628.
TreeFamiTF105310.

Family and domain databases

InterProiIPR005817. Wnt.
IPR009139. Wnt1.
IPR018161. Wnt_CS.
[Graphical view]
PANTHERiPTHR12027. PTHR12027. 1 hit.
PfamiPF00110. wnt. 1 hit.
[Graphical view]
PRINTSiPR01841. WNT1PROTEIN.
PR01349. WNTPROTEIN.
SMARTiSM00097. WNT1. 1 hit.
[Graphical view]
PROSITEiPS00246. WNT1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431C → F in OI15. 1 Publication
VAR_069627
Natural varianti177 – 1771G → C in OI15; completely fails to activate the WNT-regulated beta-catenin signaling cascade. 1 Publication
VAR_069628
Natural varianti218 – 2181C → G in OSTEOP; reduced capacity to activate canonical WNT signaling. 1 Publication
Corresponds to variant rs397514702 [ dbSNP | Ensembl ].
VAR_069629
Natural varianti235 – 2351R → W in OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the WNT-regulated beta-catenin signaling cascade. 1 Publication
Corresponds to variant rs387907359 [ dbSNP | Ensembl ].
VAR_069630
Natural varianti298 – 2981F → C in OI15. 2 Publications
VAR_069631
Natural varianti355 – 3551V → F in OI15. 1 Publication
Corresponds to variant rs387907358 [ dbSNP | Ensembl ].
VAR_069632

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.

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. Positions 85-299.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113308. 7 interactions.
STRINGi9606.ENSP00000293549.

PTM databases

iPTMnetiP04628.
PhosphoSiteiP04628.
SwissPalmiP04628.

Polymorphism and mutation databases

BioMutaiWNT1.
DMDMi139743.

Proteomic databases

PaxDbiP04628.
PRIDEiP04628.

Protocols and materials databases

DNASUi7471.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7471.
GeneCardsiWNT1.
HGNCiHGNC:12774. WNT1.
HPAiCAB025366.
MalaCardsiWNT1.
MIMi164820. gene.
166710. phenotype.
615220. phenotype.
615221. phenotype.
neXtProtiNX_P04628.
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.
OMAiNNSGRWW.
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.
PROiP04628.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125084.
CleanExiHS_WNT1.
ExpressionAtlasiP04628. baseline and differential.
GenevisibleiP04628. HS.

Family and domain databases

InterProiIPR005817. Wnt.
IPR009139. Wnt1.
IPR018161. Wnt_CS.
[Graphical view]
PANTHERiPTHR12027. PTHR12027. 1 hit.
PfamiPF00110. wnt. 1 hit.
[Graphical view]
PRINTSiPR01841. WNT1PROTEIN.
PR01349. WNTPROTEIN.
SMARTiSM00097. WNT1. 1 hit.
[Graphical view]
PROSITEiPS00246. WNT1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWNT1_HUMAN
AccessioniPrimary (citable) accession number: P04628
Secondary accession number(s): Q5U0N2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: September 7, 2016
This is version 157 of the entry and version 1 of the sequence. [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

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.