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P04628

- WNT1_HUMAN

UniProt

P04628 - WNT1_HUMAN

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Protein

Proto-oncogene Wnt-1

Gene
WNT1, INT1
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. cytokine activity Source: BHF-UCL
  2. frizzled binding Source: BHF-UCL
  3. receptor agonist activity Source: BHF-UCL
  4. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. bone development Source: UniProtKB
  2. branching involved in ureteric bud morphogenesis Source: Ensembl
  3. canonical Wnt signaling pathway Source: BHF-UCL
  4. canonical Wnt signaling pathway involved in negative regulation of apoptotic process Source: BHF-UCL
  5. cell-cell signaling Source: BHF-UCL
  6. cell fate commitment Source: RefGenome
  7. cellular response to peptide hormone stimulus Source: Ensembl
  8. central nervous system morphogenesis Source: BHF-UCL
  9. cerebellum formation Source: BHF-UCL
  10. diencephalon development Source: Ensembl
  11. embryonic axis specification Source: BHF-UCL
  12. forebrain anterior/posterior pattern specification Source: Ensembl
  13. hematopoietic stem cell proliferation Source: Ensembl
  14. hepatocyte differentiation Source: Ensembl
  15. inner ear morphogenesis Source: Ensembl
  16. midbrain development Source: BHF-UCL
  17. midbrain-hindbrain boundary maturation during brain development Source: Ensembl
  18. myoblast fusion Source: Ensembl
  19. negative regulation of BMP signaling pathway Source: AgBase
  20. negative regulation of cell aging Source: BHF-UCL
  21. negative regulation of cell-cell adhesion Source: BHF-UCL
  22. negative regulation of cell-substrate adhesion Source: BHF-UCL
  23. negative regulation of fat cell differentiation Source: BHF-UCL
  24. negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: Ensembl
  25. negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
  26. neuron differentiation Source: RefGenome
  27. neuron fate determination Source: Ensembl
  28. organ regeneration Source: Ensembl
  29. positive regulation of cell proliferation Source: BHF-UCL
  30. positive regulation of dermatome development Source: BHF-UCL
  31. positive regulation of fibroblast proliferation Source: BHF-UCL
  32. positive regulation of insulin-like growth factor receptor signaling pathway Source: BHF-UCL
  33. positive regulation of lamellipodium assembly Source: BHF-UCL
  34. positive regulation of Notch signaling pathway Source: BHF-UCL
  35. positive regulation of protein phosphorylation Source: Ensembl
  36. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  37. positive regulation of transcription, DNA-templated Source: UniProtKB
  38. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  39. response to wounding Source: UniProtKB
  40. signal transduction in response to DNA damage Source: BHF-UCL
  41. Spemann organizer formation Source: BHF-UCL
  42. spinal cord association neuron differentiation Source: Ensembl
  43. T cell differentiation in thymus Source: Ensembl
  44. ubiquitin-dependent SMAD protein catabolic process Source: Ensembl
  45. Wnt signaling pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_163710. WNT ligand biogenesis and trafficking.
REACT_172581. PCP/CE pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.
SignaLinkiP04628.

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
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:12774. WNT1.

Subcellular locationi

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. endoplasmic reticulum lumen Source: Reactome
  4. extracellular region Source: Reactome
  5. extracellular space Source: RefGenome
  6. Golgi lumen Source: Reactome
  7. plasma membrane Source: Reactome
  8. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

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.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti218 – 2181C → G in OSTEOP; reduced capacity to activate canonical WNT signaling. 1 Publication
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
VAR_069630
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.4 Publications
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
VAR_069632

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta, Proto-oncogene

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed predictionAdd
BLAST
Chaini28 – 370343Proto-oncogene Wnt-1PRO_0000041405Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi29 – 291N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi93 ↔ 104 By similarity
Disulfide bondi143 ↔ 151 By similarity
Disulfide bondi153 ↔ 170 By similarity
Disulfide bondi218 ↔ 232 By similarity
Disulfide bondi220 ↔ 227 By similarity
Lipidationi224 – 2241O-palmitoyl serine; by PORCN1 Publication
Disulfide bondi315 ↔ 330 By similarity
Glycosylationi316 – 3161N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi345 ↔ 360 By similarity
Glycosylationi346 – 3461N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi347 ↔ 357 By similarity
Disulfide bondi352 ↔ 353 By similarity
Glycosylationi359 – 3591N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Palmitoylation at Ser-224 is required for efficient binding to frizzled receptors. Palmitoylation is necessary for proper trafficking to cell surface. 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 - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP04628.
PRIDEiP04628.

PTM databases

PhosphoSiteiP04628.

Expressioni

Gene expression databases

BgeeiP04628.
CleanExiHS_WNT1.
GenevestigatoriP04628.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi113308. 7 interactions.
STRINGi9606.ENSP00000293549.

Structurei

3D structure databases

ProteinModelPortaliP04628.
SMRiP04628. Positions 85-299.

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG284879.
HOGENOMiHOG000039528.
HOVERGENiHBG001595.
InParanoidiP04628.
KOiK03209.
OMAiAIKECKW.
OrthoDBiEOG7C8GJ8.
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

MGLWALLPGW VSATLLLALA ALPAALAANS SGRWWGIVNV ASSTNLLTDS    50
KSLQLVLEPS LQLLSRKQRR LIRQNPGILH SVSGGLQSAV RECKWQFRNR 100
RWNCPTAPGP HLFGKIVNRG CRETAFIFAI TSAGVTHSVA RSCSEGSIES 150
CTCDYRRRGP GGPDWHWGGC SDNIDFGRLF GREFVDSGEK GRDLRFLMNL 200
HNNEAGRTTV FSEMRQECKC HGMSGSCTVR TCWMRLPTLR AVGDVLRDRF 250
DGASRVLYGN RGSNRASRAE LLRLEPEDPA HKPPSPHDLV YFEKSPNFCT 300
YSGRLGTAGT AGRACNSSSP ALDGCELLCC GRGHRTRTQR VTERCNCTFH 350
WCCHVSCRNC THTRVLHECL 370
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.

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
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
VAR_069630
Natural varianti298 – 2981F → C in OI15. 2 Publications
VAR_069631
Natural varianti355 – 3551V → F in OI15. 1 Publication
VAR_069632

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.3. human.

Polymorphism databases

DMDMi139743.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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. Positions 85-299.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113308. 7 interactions.
STRINGi 9606.ENSP00000293549.

PTM databases

PhosphoSitei P04628.

Polymorphism databases

DMDMi 139743.

Proteomic databases

PaxDbi P04628.
PRIDEi P04628.

Protocols and materials databases

DNASUi 7471.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000293549 ; ENSP00000293549 ; ENSG00000125084 .
GeneIDi 7471.
KEGGi hsa:7471.
UCSCi uc001rsu.3. human.

Organism-specific databases

CTDi 7471.
GeneCardsi GC12P049372.
HGNCi HGNC:12774. WNT1.
MIMi 164820. gene.
166710. phenotype.
615220. phenotype.
615221. phenotype.
neXtProti NX_P04628.
Orphaneti 85193. Idiopathic juvenile osteoporosis.
216812. Osteogenesis imperfecta type 3.
216820. Osteogenesis imperfecta type 4.
PharmGKBi PA37376.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG284879.
HOGENOMi HOG000039528.
HOVERGENi HBG001595.
InParanoidi P04628.
KOi K03209.
OMAi AIKECKW.
OrthoDBi EOG7C8GJ8.
PhylomeDBi P04628.
TreeFami TF105310.

Enzyme and pathway databases

Reactomei REACT_163710. WNT ligand biogenesis and trafficking.
REACT_172581. PCP/CE pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.
SignaLinki P04628.

Miscellaneous databases

GeneWikii WNT1.
GenomeRNAii 7471.
NextBioi 29264.
PROi P04628.
SOURCEi Search...

Gene expression databases

Bgeei P04628.
CleanExi HS_WNT1.
Genevestigatori P04628.

Family and domain databases

InterProi IPR005817. Wnt.
IPR009139. Wnt1.
IPR018161. Wnt_CS.
[Graphical view ]
PANTHERi PTHR12027. PTHR12027. 1 hit.
Pfami PF00110. wnt. 1 hit.
[Graphical view ]
PRINTSi PR01841. WNT1PROTEIN.
PR01349. WNTPROTEIN.
SMARTi SM00097. WNT1. 1 hit.
[Graphical view ]
PROSITEi PS00246. WNT1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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: PRELIMINARY CYSTEINE PALMITOYLATION, PALMITOYLATION AT SER-224.
  6. 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. Cited for: INVOLVEMENT IN OI15, VARIANT OSTEOP GLY-218, CHARACTERIZATION OF VARIANT OSTEOP GLY-218.
  8. 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.

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 3, 2014
This is version 136 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

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

External Data

Dasty 3

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