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P04628 (WNT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proto-oncogene Wnt-1
Alternative name(s):
Proto-oncogene Int-1 homolog
Gene names
Name:WNT1
Synonyms:INT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length370 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Subunit structure

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

Subcellular location

Secretedextracellular spaceextracellular matrix.

Post-translational modification

Palmitoylation at Ser-224 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-93. Palmitoylation is necessary for proper trafficking to cell surface. Ref.5

Polymorphism

Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIM: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.

Involvement in disease

Osteoporosis (OSTEOP) [MIM:166710]: A 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6 Ref.7

Osteogenesis imperfecta 15 (OI15) [MIM:615220]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Ref.8 Ref.9

Sequence similarities

Belongs to the Wnt family.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentExtracellular matrix
Secreted
   DiseaseDisease mutation
Osteogenesis imperfecta
Proto-oncogene
   DomainSignal
   Molecular functionDevelopmental protein
   PTMGlycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSpemann organizer formation

Inferred from sequence or structural similarity. Source: BHF-UCL

T cell differentiation in thymus

Inferred from electronic annotation. Source: Ensembl

bone development

Inferred from mutant phenotype Ref.6. Source: UniProtKB

branching involved in ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

canonical Wnt signaling pathway involved in negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 12154096. Source: BHF-UCL

cellular response to peptide hormone stimulus

Inferred from electronic annotation. Source: Ensembl

central nervous system morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cerebellum formation

Inferred from sequence or structural similarity. Source: BHF-UCL

diencephalon development

Inferred from electronic annotation. Source: Ensembl

embryonic axis specification

Inferred from sequence or structural similarity. Source: BHF-UCL

forebrain anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

hematopoietic stem cell proliferation

Inferred from electronic annotation. Source: Ensembl

hepatocyte differentiation

Inferred from electronic annotation. Source: Ensembl

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

midbrain development

Inferred from sequence or structural similarity. Source: BHF-UCL

midbrain-hindbrain boundary maturation during brain development

Inferred from electronic annotation. Source: Ensembl

myoblast fusion

Inferred from electronic annotation. Source: Ensembl

negative regulation of BMP signaling pathway

Inferred from mutant phenotype PubMed 16194878. Source: AgBase

negative regulation of cell aging

Inferred from direct assay PubMed 16501043. Source: BHF-UCL

negative regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 17072303. Source: BHF-UCL

negative regulation of cell-substrate adhesion

Inferred from direct assay PubMed 16501043. Source: BHF-UCL

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuron fate determination

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of Notch signaling pathway

Inferred from direct assay PubMed 16501043. Source: BHF-UCL

positive regulation of dermatome development

Inferred from direct assay PubMed 10654605. Source: BHF-UCL

positive regulation of fibroblast proliferation

Inferred from mutant phenotype PubMed 19734317. Source: BHF-UCL

positive regulation of insulin-like growth factor receptor signaling pathway

Inferred from direct assay PubMed 12154096. Source: BHF-UCL

positive regulation of lamellipodium assembly

Inferred from mutant phenotype PubMed 19756656. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 19847889. Source: UniProtKB

response to wounding

Inferred from expression pattern PubMed 17982423. Source: UniProtKB

signal transduction in response to DNA damage

Inferred from direct assay PubMed 16501043. Source: BHF-UCL

spinal cord association neuron differentiation

Inferred from electronic annotation. Source: Ensembl

ubiquitin-dependent SMAD protein catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

cell surface

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular space

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncytokine activity

Inferred from sequence or structural similarity. Source: BHF-UCL

frizzled binding

Inferred by curator PubMed 19756656. Source: BHF-UCL

receptor agonist activity

Inferred by curator PubMed 19778454. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19847889. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 370343Proto-oncogene Wnt-1
PRO_0000041405

Amino acid modifications

Lipidation931S-palmitoyl cysteine Ref.5
Lipidation2241O-palmitoyl serine; by PORCN Ref.5
Glycosylation291N-linked (GlcNAc...) Potential
Glycosylation3161N-linked (GlcNAc...) Potential
Glycosylation3461N-linked (GlcNAc...) Potential
Glycosylation3591N-linked (GlcNAc...) Potential

Natural variations

Natural variant1431C → F in OI15. Ref.9
VAR_069627
Natural variant1771G → C in OI15; completely fails to activate the WNT-regulated beta-catenin signaling cascade. Ref.6
VAR_069628
Natural variant2181C → G in OSTEOP; reduced capacity to activate canonical WNT signaling. Ref.7
VAR_069629
Natural variant2351R → W in OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the WNT-regulated beta-catenin signaling cascade. Ref.6
VAR_069630
Natural variant2981F → C in OI15. Ref.6 Ref.8
VAR_069631
Natural variant3551V → F in OI15. Ref.9
VAR_069632

Sequences

Sequence LengthMass (Da)Tools
P04628 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: F7E8111DA12E173F

FASTA37040,982
        10         20         30         40         50         60 
MGLWALLPGW VSATLLLALA ALPAALAANS SGRWWGIVNV ASSTNLLTDS KSLQLVLEPS 

        70         80         90        100        110        120 
LQLLSRKQRR LIRQNPGILH SVSGGLQSAV RECKWQFRNR RWNCPTAPGP HLFGKIVNRG 

       130        140        150        160        170        180 
CRETAFIFAI TSAGVTHSVA RSCSEGSIES CTCDYRRRGP GGPDWHWGGC SDNIDFGRLF 

       190        200        210        220        230        240 
GREFVDSGEK GRDLRFLMNL HNNEAGRTTV FSEMRQECKC HGMSGSCTVR TCWMRLPTLR 

       250        260        270        280        290        300 
AVGDVLRDRF DGASRVLYGN RGSNRASRAE LLRLEPEDPA HKPPSPHDLV YFEKSPNFCT 

       310        320        330        340        350        360 
YSGRLGTAGT AGRACNSSSP ALDGCELLCC GRGHRTRTQR VTERCNCTFH WCCHVSCRNC 

       370 
THTRVLHECL 

« Hide

References

« Hide 'large scale' references
[1]"The nucleotide sequence of the human int-1 mammary oncogene; evolutionary conservation of coding and non-coding sequences."
van Ooyen A., Kwee V., Nusse R.
EMBO J. 4:2905-2909(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[5]"Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling."
Doubravska L., Krausova M., Gradl D., Vojtechova M., Tumova L., Lukas J., Valenta T., Pospichalova V., Fafilek B., Plachy J., Sebesta O., Korinek V.
Cell. Signal. 23:837-848(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-93 AND SER-224.
[6]"Mutations in WNT1 cause different forms of bone fragility."
Keupp K., Beleggia F., Kayserili H., Barnes A.M., Steiner M., Semler O., Fischer B., Yigit G., Janda C.Y., Becker J., Breer S., Altunoglu U., Gruenhagen J., Krawitz P., Hecht J., Schinke T., Makareeva E., Lausch E. expand/collapse author list , Cankaya T., Caparros-Martin J.A., Lapunzina P., Temtamy S., Aglan M., Zabel B., Eysel P., Koerber F., Leikin S., Garcia K.C., Netzer C., Schoenau E., Ruiz-Perez V.L., Mundlos S., Amling M., Kornak U., Marini J., Wollnik B.
Am. J. Hum. Genet. 92:565-574(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INVOLVEMENT IN BMND16, VARIANTS OI15 CYS-177 AND CYS-298, VARIANT OSTEOP TRP-235, CHARACTERIZATION OF VARIANT OI15 CYS-177, CHARACTERIZATION OF VARIANT OSTEOP TRP-235.
[7]"WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta."
Laine C.M., Joeng K.S., Campeau P.M., Kiviranta R., Tarkkonen K., Grover M., Lu J.T., Pekkinen M., Wessman M., Heino T.J., Nieminen-Pihala V., Aronen M., Laine T., Kroeger H., Cole W.G., Lehesjoki A.E., Nevarez L., Krakow D. expand/collapse author list , Curry C.J., Cohn D.H., Gibbs R.A., Lee B.H., Maekitie O.
N. Engl. J. Med. 368:1809-1816(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN OI15, VARIANT OSTEOP GLY-218, CHARACTERIZATION OF VARIANT OSTEOP GLY-218.
[8]"WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta."
Pyott S.M., Tran T.T., Leistritz D.F., Pepin M.G., Mendelsohn N.J., Temme R.T., Fernandez B.A., Elsayed S.M., Elsobky E., Verma I., Nair S., Turner E.H., Smith J.D., Jarvik G.P., Byers P.H.
Am. J. Hum. Genet. 92:590-597(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OI15 CYS-298.
[9]"Mutations in WNT1 are a cause of osteogenesis imperfecta."
Fahiminiya S., Majewski J., Mort J., Moffatt P., Glorieux F.H., Rauch F.
J. Med. Genet. 50:345-348(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OI15 PHE-143 AND PHE-355.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRTVHUT1. A24674.
RefSeqNP_005421.1. NM_005430.3.
UniGeneHs.248164.

3D structure databases

ProteinModelPortalP04628.
SMRP04628. Positions 73-369.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113308. 7 interactions.
STRING9606.ENSP00000293549.

PTM databases

PhosphoSiteP04628.

Polymorphism databases

DMDM139743.

Proteomic databases

PaxDbP04628.
PRIDEP04628.

Protocols and materials databases

DNASU7471.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293549; ENSP00000293549; ENSG00000125084.
GeneID7471.
KEGGhsa:7471.
UCSCuc001rsu.3. human.

Organism-specific databases

CTD7471.
GeneCardsGC12P049372.
HGNCHGNC:12774. WNT1.
MIM164820. gene.
166710. phenotype.
615220. phenotype.
615221. phenotype.
neXtProtNX_P04628.
Orphanet85193. Idiopathic juvenile osteoporosis.
216812. Osteogenesis imperfecta type 3.
216820. Osteogenesis imperfecta type 4.
PharmGKBPA37376.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG284879.
HOGENOMHOG000039528.
HOVERGENHBG001595.
InParanoidP04628.
KOK03209.
OMAAIKECKW.
OrthoDBEOG7C8GJ8.
PhylomeDBP04628.
TreeFamTF105310.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkP04628.

Gene expression databases

BgeeP04628.
CleanExHS_WNT1.
GenevestigatorP04628.

Family and domain databases

InterProIPR005817. Wnt.
IPR009139. Wnt1.
IPR018161. Wnt_CS.
[Graphical view]
PANTHERPTHR12027. PTHR12027. 1 hit.
PTHR12027:SF15. PTHR12027:SF15. 1 hit.
PfamPF00110. wnt. 1 hit.
[Graphical view]
PRINTSPR01841. WNT1PROTEIN.
PR01349. WNTPROTEIN.
SMARTSM00097. WNT1. 1 hit.
[Graphical view]
PROSITEPS00246. WNT1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiWNT1.
GenomeRNAi7471.
NextBio29264.
PROP04628.
SOURCESearch...

Entry information

Entry nameWNT1_HUMAN
AccessionPrimary (citable) accession number: P04628
Secondary accession number(s): Q5U0N2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: March 19, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM