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P04628

- WNT1_HUMAN

UniProt

P04628 - WNT1_HUMAN

Protein

Proto-oncogene Wnt-1

Gene

WNT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    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

    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

    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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    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.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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 – 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-palmitoyl serine; by PORCN1 Publication
    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

    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.By similarity

    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

    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

    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: October 1, 2014
    This is version 137 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