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Protein

Proto-oncogene Wnt-1

Gene

Wnt1

Organism
Mus musculus (Mouse)
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. Proeminent role in the induction of the mesencephalon and cerebellum. May play a crucial role in the morphogenesis of the neural tube and/or the early stages of CNS development. Has a role in osteoblast function and bone development (By similarity).By similarity

GO - Molecular functioni

  1. cytokine activity Source: BHF-UCL
  2. frizzled binding Source: GO_Central
  3. protein domain specific binding Source: UniProtKB
  4. receptor binding Source: MGI
  5. transcription regulatory region DNA binding Source: MGI

GO - Biological processi

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

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_295052. WNT ligand biogenesis and trafficking.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_317277. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_333985. PCP/CE pathway.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_335672. TCF dependent signaling in response to WNT.

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene Wnt-1
Alternative name(s):
Proto-oncogene Int-1
Gene namesi
Name:Wnt1
Synonyms:Int-1, Wnt-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:98953. Wnt1.

Subcellular locationi

GO - Cellular componenti

  1. cell surface Source: MGI
  2. cytoplasm Source: MGI
  3. endoplasmic reticulum lumen Source: Reactome
  4. extracellular space Source: GO_Central
  5. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Many mouse mammary tumors induced by mouse mammary tumor virus (MMTV) contain a provirus integrated into a host cell region which has been named INT-1 (now Wnt1).

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 370343Proto-oncogene Wnt-1PRO_0000041406Add
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 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

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 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PRIDEiP04426.

PTM databases

PhosphoSiteiP04426.

Expressioni

Tissue specificityi

Testis and mid-gestational embryos. In the testis, detected only in postmeiotic germ cells undergoing differentiation from round spermatids into mature spermatozoa. In the embryos, expression is restricted to the developing CNS in regions of the neural tube other than the telencephalon. Expressed in osteoblast; expression levels increase with advancing osteoblast differentiation. Expressed in the brain, femur, spleen, and hematopoietic bone marrow.3 Publications

Developmental stagei

Accumulates throughout the neural plate at the anterior head folds of the 9 day embryo but only at its lateral tips in more posterior regions. Following neural tube closure, expression is restricted to specific regions of the dorsal wall of the brain ventricles and spinal cord, the ventral wall of the midbrain and the diencephalon, and the lateral walls of the neuroepithelium at the midbrain-hindbrain junction.1 Publication

Gene expression databases

BgeeiP04426.
CleanExiMM_WNT1.
ExpressionAtlasiP04426. baseline.
GenevestigatoriP04426.

Interactioni

Subunit structurei

Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3. Interacts with WLS.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KlO350822EBI-1570911,EBI-1570828
LRP6O755812EBI-1570911,EBI-910915From a different organism.

Protein-protein interaction databases

BioGridi204567. 9 interactions.
DIPiDIP-39896N.
IntActiP04426. 2 interactions.
STRINGi10090.ENSMUSP00000023734.

Structurei

3D structure databases

ProteinModelPortaliP04426.
SMRiP04426. Positions 85-299.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG284879.
HOGENOMiHOG000039528.
HOVERGENiHBG001595.
InParanoidiP04426.
KOiK03209.
OMAiAIKECKW.
OrthoDBiEOG7C8GJ8.
PhylomeDBiP04426.
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.

P04426-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLWALLPSW VSTTLLLALT ALPAALAANS SGRWWGIVNI 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):41,086
Last modified:August 13, 1987 - v1
Checksum:i02EEB23109231A40
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02593 Genomic DNA. Translation: AAA39321.1.
M11943 mRNA. Translation: AAA39322.1.
BC005449 mRNA. Translation: AAH05449.1.
CCDSiCCDS27807.1.
PIRiA23447. TVMST1.
RefSeqiNP_067254.1. NM_021279.4.
XP_006520953.1. XM_006520890.2.
UniGeneiMm.1123.

Genome annotation databases

EnsembliENSMUST00000023734; ENSMUSP00000023734; ENSMUSG00000022997.
GeneIDi22408.
KEGGimmu:22408.
UCSCiuc007xnx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02593 Genomic DNA. Translation: AAA39321.1.
M11943 mRNA. Translation: AAA39322.1.
BC005449 mRNA. Translation: AAH05449.1.
CCDSiCCDS27807.1.
PIRiA23447. TVMST1.
RefSeqiNP_067254.1. NM_021279.4.
XP_006520953.1. XM_006520890.2.
UniGeneiMm.1123.

3D structure databases

ProteinModelPortaliP04426.
SMRiP04426. Positions 85-299.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204567. 9 interactions.
DIPiDIP-39896N.
IntActiP04426. 2 interactions.
STRINGi10090.ENSMUSP00000023734.

PTM databases

PhosphoSiteiP04426.

Proteomic databases

PRIDEiP04426.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023734; ENSMUSP00000023734; ENSMUSG00000022997.
GeneIDi22408.
KEGGimmu:22408.
UCSCiuc007xnx.1. mouse.

Organism-specific databases

CTDi7471.
MGIiMGI:98953. Wnt1.

Phylogenomic databases

eggNOGiNOG284879.
HOGENOMiHOG000039528.
HOVERGENiHBG001595.
InParanoidiP04426.
KOiK03209.
OMAiAIKECKW.
OrthoDBiEOG7C8GJ8.
PhylomeDBiP04426.
TreeFamiTF105310.

Enzyme and pathway databases

ReactomeiREACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
REACT_295052. WNT ligand biogenesis and trafficking.
REACT_309805. Transcriptional regulation of white adipocyte differentiation.
REACT_317277. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_333985. PCP/CE pathway.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_335672. TCF dependent signaling in response to WNT.

Miscellaneous databases

NextBioi302801.
PROiP04426.
SOURCEiSearch...

Gene expression databases

BgeeiP04426.
CleanExiMM_WNT1.
ExpressionAtlasiP04426. baseline.
GenevestigatoriP04426.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact."
    Ooyen A.V., Nusse R.
    Cell 39:233-240(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C3H.
  2. "Nucleotide sequence and expression in vitro of cDNA derived from mRNA of int-1, a provirally activated mouse mammary oncogene."
    Fung Y.-K.T., Shackleford G.M., Brown A.M.C., Sanders G.S., Varmus H.E.
    Mol. Cell. Biol. 5:3337-3344(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development."
    Gavin B.J., McMahon J.A., McMahon A.P.
    Genes Dev. 4:2319-2332(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE.
  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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech II.
  5. "Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development."
    Thomas K.R., Capecchi M.R.
    Nature 346:847-850(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE FUNCTION.
  6. "Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo."
    Wilkinson D.G., Bailes J.A., McMahon A.P.
    Cell 50:79-88(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
    Strain: CBA/Ca.
    Tissue: Embryo.
  7. "Expression of the proto-oncogene int-1 is restricted to postmeiotic male germ cells and the neural tube of mid-gestational embryos."
    Shackleford G.M., Varmus H.E.
    Cell 50:89-95(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
    Strain: ICR.
  8. "The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family."
    Tanaka K., Okabayashi H., Asashima M., Perrimon N., Kadowaki T.
    Eur. J. Biochem. 267:4300-4311(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PORCN.
  9. "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth."
    Lu W., Yamamoto V., Ortega B., Baltimore D.
    Cell 119:97-108(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract."
    Liu Y., Shi J., Lu C.C., Wang Z.B., Lyuksyutova A.I., Song X.J., Zou Y.
    Nat. Neurosci. 8:1151-1159(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."
    Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.
    J. Biol. Chem. 281:13247-13257(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RSPO1; RSPO2 AND RSPO3.
  12. "Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation."
    Fu J., Jiang M., Mirando A.J., Yu H.-M., Hsu W.
    Proc. Natl. Acad. Sci. U.S.A. 106:18598-18603(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WLS.
  13. Cited for: TISSUE SPECIFICITY.
  14. Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiWNT1_MOUSE
AccessioniPrimary (citable) accession number: P04426
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: April 1, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.