UniProtKB - P04628 (WNT1_HUMAN)
Protein
Proto-oncogene Wnt-1
Gene
WNT1
Organism
Homo sapiens (Human)
Status
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
GO - Biological processi
- animal organ regeneration Source: Ensembl
- astrocyte-dopaminergic neuron signaling Source: Ensembl
- beta-catenin destruction complex disassembly Source: Reactome
- bone development Source: UniProtKB
- branching involved in ureteric bud morphogenesis Source: Ensembl
- canonical Wnt signaling pathway Source: BHF-UCL
- canonical Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- cell-cell signaling Source: BHF-UCL
- cell fate commitment Source: GO_Central
- cell proliferation in midbrain Source: Ensembl
- cellular response to peptide hormone stimulus Source: Ensembl
- central nervous system morphogenesis Source: BHF-UCL
- cerebellum formation Source: BHF-UCL
- diencephalon development Source: Ensembl
- embryonic axis specification Source: BHF-UCL
- embryonic brain development Source: Ensembl
- forebrain anterior/posterior pattern specification Source: Ensembl
- hematopoietic stem cell proliferation Source: Ensembl
- hepatocyte differentiation Source: Ensembl
- inner ear morphogenesis Source: Ensembl
- midbrain development Source: BHF-UCL
- midbrain-hindbrain boundary maturation during brain development Source: Ensembl
- myoblast fusion Source: Ensembl
- negative regulation of apoptotic process Source: BHF-UCL
- negative regulation of BMP signaling pathway Source: AgBase
- negative regulation of cell aging Source: BHF-UCL
- negative regulation of cell-cell adhesion Source: BHF-UCL
- negative regulation of cell-substrate adhesion Source: BHF-UCL
- negative regulation of fat cell differentiation Source: BHF-UCL
- negative regulation of oxidative stress-induced neuron death Source: Ensembl
- negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
- negative regulation of ubiquitin-dependent protein catabolic process Source: Ensembl
- neuron differentiation Source: GO_Central
- neuron fate determination Source: Ensembl
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of dermatome development Source: BHF-UCL
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of fibroblast proliferation Source: BHF-UCL
- positive regulation of insulin-like growth factor receptor signaling pathway Source: BHF-UCL
- positive regulation of lamellipodium assembly Source: BHF-UCL
- positive regulation of Notch signaling pathway Source: BHF-UCL
- positive regulation of protein phosphorylation Source: Ensembl
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: Ensembl
- response to wounding Source: UniProtKB
- signal transduction in response to DNA damage Source: BHF-UCL
- Spemann organizer formation Source: BHF-UCL
- spinal cord association neuron differentiation Source: Ensembl
- T cell differentiation in thymus Source: Ensembl
- ubiquitin-dependent SMAD protein catabolic process Source: Ensembl
- Wnt signaling pathway Source: GO_Central
- Wnt signaling pathway, planar cell polarity pathway Source: Reactome
- Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
Keywordsi
Molecular function | Developmental protein |
Biological process | Wnt signaling pathway |
Enzyme and pathway databases
Reactomei | R-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 |
SignaLinki | P04628 |
SIGNORi | P04628 |
Names & Taxonomyi
Protein namesi | Recommended name: Proto-oncogene Wnt-1Alternative name(s): Proto-oncogene Int-1 homolog |
Gene namesi | Name:WNT1 Synonyms:INT1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000125084.11 |
HGNCi | HGNC:12774 WNT1 |
MIMi | 164820 gene |
neXtProti | NX_P04628 |
Subcellular locationi
Extracellular region or secreted
- extracellular matrix Curated
- Secreted 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: Reactome
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Golgi apparatus
- Golgi lumen Source: Reactome
Plasma Membrane
- plasma membrane Source: Reactome
Other locations
- cell surface Source: Ensembl
- cytoplasm Source: UniProtKB
- endocytic vesicle membrane Source: Reactome
Keywords - Cellular componenti
Extracellular matrix, SecretedPathology & 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:166710Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069629 | 218 | C → G in OSTEOP; reduced capacity to activate canonical Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397514702EnsemblClinVar. | 1 | |
Natural variantiVAR_069630 | 235 | R → 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:615220Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079407 | 123 | E → D in OI15; detected in a compound heterozygote also carrying G-153; reduced capacity to activate canonical Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_069627 | 143 | C → F in OI15. 1 Publication | 1 | |
Natural variantiVAR_079408 | 153 | C → G in OI15; detected in a compound heterozygote also carrying D-123; reduced capacity to activate canonical Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_069628 | 177 | G → C in OI15; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 Publication | 1 | |
Natural variantiVAR_069631 | 298 | F → C in OI15. 2 Publications | 1 | |
Natural variantiVAR_069632 | 355 | V → F in OI15. 1 PublicationCorresponds to variant dbSNP:rs387907358EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutation, Osteogenesis imperfecta, Proto-oncogeneOrganism-specific databases
DisGeNETi | 7471 |
MalaCardsi | WNT1 |
MIMi | 166710 phenotype 615220 phenotype 615221 phenotype |
OpenTargetsi | ENSG00000125084 |
Orphaneti | 85193 Idiopathic juvenile osteoporosis 216812 Osteogenesis imperfecta type 3 216820 Osteogenesis imperfecta type 4 |
PharmGKBi | PA37376 |
Polymorphism and mutation databases
BioMutai | WNT1 |
DMDMi | 139743 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | Sequence analysisAdd BLAST | 27 | |
ChainiPRO_0000041405 | 28 – 370 | Proto-oncogene Wnt-1Add BLAST | 343 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 29 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 93 ↔ 104 | By similarity | ||
Disulfide bondi | 143 ↔ 151 | By similarity | ||
Disulfide bondi | 153 ↔ 170 | By similarity | ||
Disulfide bondi | 218 ↔ 232 | By similarity | ||
Disulfide bondi | 220 ↔ 227 | By similarity | ||
Lipidationi | 224 | O-palmitoleoyl serine; by PORCNBy similarity | 1 | |
Disulfide bondi | 299 ↔ 330 | By similarity | ||
Disulfide bondi | 315 ↔ 325 | By similarity | ||
Glycosylationi | 316 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 329 ↔ 369 | By similarity | ||
Disulfide bondi | 345 ↔ 360 | By similarity | ||
Glycosylationi | 346 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 347 ↔ 357 | By similarity | ||
Disulfide bondi | 352 ↔ 353 | By similarity | ||
Glycosylationi | 359 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
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, LipoproteinProteomic databases
jPOSTi | P04628 |
PaxDbi | P04628 |
PeptideAtlasi | P04628 |
PRIDEi | P04628 |
ProteomicsDBi | 51722 |
PTM databases
iPTMneti | P04628 |
PhosphoSitePlusi | P04628 |
SwissPalmi | P04628 |
Expressioni
Gene expression databases
Bgeei | ENSG00000125084 Expressed in 40 organ(s), highest expression level in nucleus accumbens |
ExpressionAtlasi | P04628 baseline and differential |
Genevisiblei | P04628 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
- 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
Protein-protein interaction databases
BioGridi | 113308, 9 interactors |
STRINGi | 9606.ENSP00000293549 |
Structurei
3D structure databases
ProteinModelPortali | P04628 |
SMRi | P04628 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Sequence similaritiesi
Belongs to the Wnt family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3913 Eukaryota ENOG410XQZ1 LUCA |
GeneTreei | ENSGT00940000160329 |
HOGENOMi | HOG000039528 |
HOVERGENi | HBG001595 |
InParanoidi | P04628 |
KOi | K03209 |
OMAi | WNCPTAS |
OrthoDBi | 624528at2759 |
PhylomeDBi | P04628 |
TreeFami | TF105310 |
Family and domain databases
InterProi | View protein in InterPro IPR005817 Wnt IPR009139 Wnt1 IPR018161 Wnt_CS |
PANTHERi | PTHR12027 PTHR12027, 2 hits |
Pfami | View protein in Pfam PF00110 wnt, 1 hit |
PRINTSi | PR01841 WNT1PROTEIN PR01349 WNTPROTEIN |
SMARTi | View protein in SMART SM00097 WNT1, 1 hit |
PROSITEi | View protein in PROSITE PS00246 WNT1, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P04628-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A087WXR9 | A0A087WXR9_HUMAN | Protein Wnt | WNT1 | 359 | Annotation 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079407 | 123 | E → D in OI15; detected in a compound heterozygote also carrying G-153; reduced capacity to activate canonical Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_069627 | 143 | C → F in OI15. 1 Publication | 1 | |
Natural variantiVAR_079408 | 153 | C → G in OI15; detected in a compound heterozygote also carrying D-123; reduced capacity to activate canonical Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_069628 | 177 | G → C in OI15; completely fails to activate the Wnt-regulated beta-catenin signaling cascade. 1 Publication | 1 | |
Natural variantiVAR_069629 | 218 | C → G in OSTEOP; reduced capacity to activate canonical Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397514702EnsemblClinVar. | 1 | |
Natural variantiVAR_069630 | 235 | R → 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_069631 | 298 | F → C in OI15. 2 Publications | 1 | |
Natural variantiVAR_069632 | 355 | V → 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 |
CCDSi | CCDS8776.1 |
PIRi | A24674 TVHUT1 |
RefSeqi | NP_005421.1, NM_005430.3 |
UniGenei | Hs.248164 |
Genome annotation databases
Ensembli | ENST00000293549; ENSP00000293549; ENSG00000125084 |
GeneIDi | 7471 |
KEGGi | hsa:7471 |
UCSCi | uc001rsu.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 |
CCDSi | CCDS8776.1 |
PIRi | A24674 TVHUT1 |
RefSeqi | NP_005421.1, NM_005430.3 |
UniGenei | Hs.248164 |
3D structure databases
ProteinModelPortali | P04628 |
SMRi | P04628 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 113308, 9 interactors |
STRINGi | 9606.ENSP00000293549 |
PTM databases
iPTMneti | P04628 |
PhosphoSitePlusi | P04628 |
SwissPalmi | P04628 |
Polymorphism and mutation databases
BioMutai | WNT1 |
DMDMi | 139743 |
Proteomic databases
jPOSTi | P04628 |
PaxDbi | P04628 |
PeptideAtlasi | P04628 |
PRIDEi | P04628 |
ProteomicsDBi | 51722 |
Protocols and materials databases
DNASUi | 7471 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000293549; ENSP00000293549; ENSG00000125084 |
GeneIDi | 7471 |
KEGGi | hsa:7471 |
UCSCi | uc001rsu.4 human |
Organism-specific databases
CTDi | 7471 |
DisGeNETi | 7471 |
EuPathDBi | HostDB:ENSG00000125084.11 |
GeneCardsi | WNT1 |
HGNCi | HGNC:12774 WNT1 |
MalaCardsi | WNT1 |
MIMi | 164820 gene 166710 phenotype 615220 phenotype 615221 phenotype |
neXtProti | NX_P04628 |
OpenTargetsi | ENSG00000125084 |
Orphaneti | 85193 Idiopathic juvenile osteoporosis 216812 Osteogenesis imperfecta type 3 216820 Osteogenesis imperfecta type 4 |
PharmGKBi | PA37376 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3913 Eukaryota ENOG410XQZ1 LUCA |
GeneTreei | ENSGT00940000160329 |
HOGENOMi | HOG000039528 |
HOVERGENi | HBG001595 |
InParanoidi | P04628 |
KOi | K03209 |
OMAi | WNCPTAS |
OrthoDBi | 624528at2759 |
PhylomeDBi | P04628 |
TreeFami | TF105310 |
Enzyme and pathway databases
Reactomei | R-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 |
SignaLinki | P04628 |
SIGNORi | P04628 |
Miscellaneous databases
GeneWikii | WNT1 |
GenomeRNAii | 7471 |
PROi | PR:P04628 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125084 Expressed in 40 organ(s), highest expression level in nucleus accumbens |
ExpressionAtlasi | P04628 baseline and differential |
Genevisiblei | P04628 HS |
Family and domain databases
InterProi | View protein in InterPro IPR005817 Wnt IPR009139 Wnt1 IPR018161 Wnt_CS |
PANTHERi | PTHR12027 PTHR12027, 2 hits |
Pfami | View protein in Pfam PF00110 wnt, 1 hit |
PRINTSi | PR01841 WNT1PROTEIN PR01349 WNTPROTEIN |
SMARTi | View protein in SMART SM00097 WNT1, 1 hit |
PROSITEi | View protein in PROSITE PS00246 WNT1, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | WNT1_HUMAN | |
Accessioni | P04628Primary (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: | February 13, 2019 | |
This is version 179 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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 proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations