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P22561

- WT1_MOUSE

UniProt

P22561 - WT1_MOUSE

Protein

Wilms tumor protein homolog

Gene

Wt1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Aug 1991)
      Previous versions | rss
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    Functioni

    Transcription factor that plays an important role in cellular development and cell survival. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors. Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing. Isoform 1 has lower affinity for DNA, and can bind RNA.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei424 – 4241Important for interaction with target DNABy similarity
    Sitei430 – 4301Important for interaction with target DNABy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri323 – 34725C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri353 – 37725C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri383 – 40523C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri414 – 43825C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. C2H2 zinc finger domain binding Source: UniProtKB
    2. double-stranded DNA binding Source: MGI
    3. protein binding Source: UniProtKB
    4. RNA binding Source: MGI
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: UniProtKB
    6. sequence-specific DNA binding Source: UniProtKB
    7. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    8. transcription regulatory region DNA binding Source: UniProtKB
    9. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. adrenal cortex formation Source: UniProtKB
    2. adrenal gland development Source: UniProtKB
    3. apoptotic DNA fragmentation Source: UniProtKB
    4. branching involved in ureteric bud morphogenesis Source: UniProtKB
    5. camera-type eye development Source: MGI
    6. cardiac muscle cell fate commitment Source: BHF-UCL
    7. cellular response to cAMP Source: RefGenome
    8. cellular response to gonadotropin stimulus Source: UniProtKB
    9. coronary vasculature development Source: DFLAT
    10. diaphragm development Source: UniProtKB
    11. epithelial cell differentiation Source: UniProtKB
    12. germ cell development Source: MGI
    13. glomerular visceral epithelial cell development Source: UniProtKB
    14. glomerular visceral epithelial cell differentiation Source: UniProtKB
    15. glomerulus development Source: UniProtKB
    16. gonad development Source: UniProtKB
    17. heart development Source: UniProtKB
    18. kidney development Source: UniProtKB
    19. male genitalia development Source: UniProtKB
    20. male gonad development Source: MGI
    21. mesenchymal to epithelial transition Source: UniProtKB
    22. mesonephros development Source: MGI
    23. metanephric comma-shaped body morphogenesis Source: UniProtKB
    24. metanephric mesenchyme development Source: UniProtKB
    25. metanephric S-shaped body morphogenesis Source: UniProtKB
    26. metanephros development Source: UniProtKB
    27. negative regulation of apoptotic process Source: UniProtKB
    28. negative regulation of cell growth Source: UniProtKB
    29. negative regulation of female gonad development Source: UniProtKB
    30. negative regulation of mesenchymal cell apoptotic process involved in metanephros development Source: MGI
    31. negative regulation of metanephric glomerular mesangial cell proliferation Source: UniProtKB
    32. negative regulation of transcription, DNA-templated Source: UniProtKB
    33. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    34. negative regulation of translation Source: UniProtKB
    35. positive regulation of heart growth Source: UniProtKB
    36. positive regulation of male gonad development Source: UniProtKB
    37. positive regulation of metanephric ureteric bud development Source: UniProtKB
    38. positive regulation of transcription, DNA-templated Source: UniProtKB
    39. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    40. posterior mesonephric tubule development Source: UniProtKB
    41. regulation of organ formation Source: UniProtKB
    42. regulation of transcription, DNA-templated Source: MGI
    43. regulation of transcription from RNA polymerase II promoter Source: MGI
    44. RNA splicing Source: UniProtKB
    45. sex determination Source: MGI
    46. thorax and anterior abdomen determination Source: UniProtKB
    47. tissue development Source: MGI
    48. ureteric bud development Source: UniProtKB
    49. vasculogenesis Source: MGI
    50. visceral serous pericardium development Source: UniProtKB

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, RNA-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Wilms tumor protein homolog
    Gene namesi
    Name:Wt1
    Synonyms:Wt-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:98968. Wt1.

    Subcellular locationi

    Nucleus. Nucleusnucleolus By similarity. Cytoplasm. Nucleus speckle
    Note: Shuttles between nucleus and cytoplasm.

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nuclear speck Source: UniProtKB
    3. nucleolus Source: UniProtKB-SubCell
    4. nucleoplasm Source: UniProtKB
    5. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 449449Wilms tumor protein homologPRO_0000047132Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki73 – 73Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Cross-linki177 – 177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Proteomic databases

    PaxDbiP22561.
    PRIDEiP22561.

    PTM databases

    PhosphoSiteiP22561.

    Expressioni

    Tissue specificityi

    Detected in neurons of the embryonic dorsal root ganglion and in Sertoli cells of the adult testis (at protein level). Detected in kidney.1 Publication

    Developmental stagei

    Expressed in the coelomic epithelium and within some mesonephric tubules of the genital ridge at 10 dpc. Expressed during kidney development.2 Publications

    Gene expression databases

    CleanExiMM_WT1.
    GenevestigatoriP22561.

    Interactioni

    Subunit structurei

    Interacts with ZNF224 via the zinc-finger region. Interacts with WTAP, AMER1 and SRY. Interacts with RBM4 By similarity. Homodimer. Interacts with WTIP. Interacts with actively translating polysomes. Detected in nuclear ribonucleoprotein (mRNP) particles. Interacts with U2AF2. Interacts with HNRNPU via the zinc-finger region. Isoform 1 and isoform 3 interacts with CITED2.By similarity5 Publications

    Protein-protein interaction databases

    BioGridi204587. 2 interactions.
    IntActiP22561. 1 interaction.
    MINTiMINT-243493.

    Structurei

    3D structure databases

    ProteinModelPortaliP22561.
    SMRiP22561. Positions 293-438.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni367 – 38115Important for interaction with target DNABy similarityAdd
    BLAST
    Regioni393 – 4019Important for interaction with target DNABy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi408 – 4103KTS motifBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi28 – 8356Pro-richAdd
    BLAST

    Sequence similaritiesi

    Contains 4 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri323 – 34725C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri353 – 37725C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri383 – 40523C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri414 – 43825C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5048.
    HOGENOMiHOG000230937.
    HOVERGENiHBG006960.
    InParanoidiA2A402.
    PhylomeDBiP22561.

    Family and domain databases

    Gene3Di3.30.160.60. 4 hits.
    InterProiIPR017987. Wilms_tumour.
    IPR000976. Wilms_tumour_N.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF02165. WT1. 1 hit.
    PF00096. zf-C2H2. 1 hit.
    [Graphical view]
    PRINTSiPR00049. WILMSTUMOUR.
    SMARTiSM00355. ZnF_C2H2. 4 hits.
    [Graphical view]
    PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view]

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform 1 (identifier: P22561-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGSDVRDLNA LLPAVSSLGG GGGGCGLPVS GARQWAPVLD FAPPGASAYG    50
    SLGGPAPPPA PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTLHFSGQF 100
    TGTAGACRYG PFGPPPPSQA SSGQARMFPN APYLPSCLES QPTIRNQGYS 150
    TVTFDGAPSY GHTPSHHAAQ FPNHSFKHED PMGQQGSLGE QQYSVPPPVY 200
    GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ MNLGATLKGM 250
    AAGSSSSVKW TEGQSNHGIG YESENHTAPI LCGAQYRIHT HGVFRGIQDV 300
    RRVSGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE 350
    KPYQCDFKDC ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT 400
    HTRTHTGKTS EKPFSCRWHS CQKKFARSDE LVRHHNMHQR NMTKLHVAL 449

    Note: Detected in nucleus speckle, may bind mRNA.

    Length:449
    Mass (Da):49,246
    Last modified:August 1, 1991 - v1
    Checksum:i962381E9C8D7A380
    GO
    Isoform 2 (identifier: P22561-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         250-266: Missing.
         408-410: Missing.

    Show »
    Length:429
    Mass (Da):47,221
    Checksum:iE53D995E5773F9AA
    GO
    Isoform 3 (identifier: P22561-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         250-266: Missing.

    Show »
    Length:432
    Mass (Da):47,537
    Checksum:iF10430FD2220373E
    GO
    Isoform 4 (identifier: P22561-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         408-410: Missing.

    Note: Detected in nucleoplasm, probably functions as transcription factor.

    Show »
    Length:446
    Mass (Da):48,930
    Checksum:iE1D76ECAE93FB51D
    GO
    Isoform 5 (identifier: P22561-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MDFLLSQEPASTCVPEPASQHTLRREPGCVQQPEQPGDRGPRSAWAKSSAENPQDRRSGEPSASEPHLM

    Note: Produced by alternative initiation of isoform 1. Extended N-terminus.

    Show »
    Length:517
    Mass (Da):56,651
    Checksum:i1752F2E98A0983E4
    GO
    Isoform 6 (identifier: P22561-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MDFLLSQEPASTCVPEPASQHTLRREPGCVQQPEQPGDRGPRSAWAKSSAENPQDRRSGEPSASEPHLM
         250-266: Missing.

    Note: Produced by alternative initiation of isoform 1. Extended N-terminus.

    Show »
    Length:500
    Mass (Da):54,943
    Checksum:iBB0560BE625E4B4D
    GO

    Sequence cautioni

    The sequence described in 1 Publication differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti33 – 331R → A in CAM18169. (PubMed:19468303)Curated
    Sequence conflicti269 – 2691I → T in CAM18169. (PubMed:19468303)Curated
    Sequence conflicti446 – 4472HV → QL in CAM18169. (PubMed:19468303)Curated

    RNA editingi

    Partially edited.By similarity

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti281 – 2811L → P in RNA edited version.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MDFLLSQEPASTCVPEPASQ HTLRREPGCVQQPEQPGDRG PRSAWAKSSAENPQDRRSGE PSASEPHLM in isoform 5 and isoform 6. CuratedVSP_037585
    Alternative sequencei250 – 26617Missing in isoform 2, isoform 3 and isoform 6. 1 PublicationVSP_006868Add
    BLAST
    Alternative sequencei408 – 4103Missing in isoform 2 and isoform 4. 1 PublicationVSP_006869

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55512 mRNA. Translation: AAA40573.1.
    AL512584 Genomic DNA. Translation: CAM18169.2.
    CCDSiCCDS16496.2. [P22561-5]
    PIRiA39692.
    UniGeneiMm.389339.

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, RNA editing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M55512 mRNA. Translation: AAA40573.1 .
    AL512584 Genomic DNA. Translation: CAM18169.2 .
    CCDSi CCDS16496.2. [P22561-5 ]
    PIRi A39692.
    UniGenei Mm.389339.

    3D structure databases

    ProteinModelPortali P22561.
    SMRi P22561. Positions 293-438.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204587. 2 interactions.
    IntActi P22561. 1 interaction.
    MINTi MINT-243493.

    PTM databases

    PhosphoSitei P22561.

    Proteomic databases

    PaxDbi P22561.
    PRIDEi P22561.

    Protocols and materials databases

    DNASUi 22431.
    Structural Biology Knowledgebase Search...

    Organism-specific databases

    MGIi MGI:98968. Wt1.

    Phylogenomic databases

    eggNOGi COG5048.
    HOGENOMi HOG000230937.
    HOVERGENi HBG006960.
    InParanoidi A2A402.
    PhylomeDBi P22561.

    Miscellaneous databases

    NextBioi 302875.
    PROi P22561.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_WT1.
    Genevestigatori P22561.

    Family and domain databases

    Gene3Di 3.30.160.60. 4 hits.
    InterProi IPR017987. Wilms_tumour.
    IPR000976. Wilms_tumour_N.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF02165. WT1. 1 hit.
    PF00096. zf-C2H2. 1 hit.
    [Graphical view ]
    PRINTSi PR00049. WILMSTUMOUR.
    SMARTi SM00355. ZnF_C2H2. 4 hits.
    [Graphical view ]
    PROSITEi PS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 4 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development."
      Buckler A.J., Pelletier J., Haber D.A., Glaser T., Housman D.E.
      Mol. Cell. Biol. 11:1707-1712(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "A non-AUG translational initiation event generates novel WT1 isoforms."
      Bruening W., Pelletier J.
      J. Biol. Chem. 271:8646-8654(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE INITIATION, ALTERNATIVE SPLICING (ISOFORMS 5 AND 6).
    4. "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes."
      Davies R.C., Calvio C., Bratt E., Larsson S.H., Lamond A.I., Hastie N.D.
      Genes Dev. 12:3217-3225(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH U2AF2.
    5. "The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes."
      Niksic M., Slight J., Sanford J.R., Caceres J.F., Hastie N.D.
      Hum. Mol. Genet. 13:463-471(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, RNA-BINDING, INTERACTION WITH POLYSOMES.
    6. Cited for: INTERACTION WITH WTIP.
    7. "The Wilms tumour suppressor protein WT1 (+KTS isoform) binds alpha-actinin 1 mRNA via its zinc-finger domain."
      Morrison A.A., Venables J.P., Dellaire G., Ladomery M.R.
      Biochem. Cell Biol. 84:789-798(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene."
      Dame C., Kirschner K.M., Bartz K.V., Wallach T., Hussels C.S., Scholz H.
      Blood 107:4282-4290(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    9. "The Wilms tumor suppressor Wt1 promotes cell adhesion through transcriptional activation of the alpha4integrin gene."
      Kirschner K.M., Wagner N., Wagner K.-D., Wellmann S., Scholz H.
      J. Biol. Chem. 281:31930-31939(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    10. "Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage."
      Val P., Martinez-Barbera J.P., Swain A.
      Development 134:2349-2358(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CITED2, DEVELOPMENTAL STAGE.
    11. "hnRNP-U directly interacts with WT1 and modulates WT1 transcriptional activation."
      Spraggon L., Dudnakova T., Slight J., Lustig-Yariv O., Cotterell J., Hastie N., Miles C.
      Oncogene 26:1484-1491(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HNRNPU, SUBCELLULAR LOCATION.
    12. "The transcription co-factor CITED2 functions during sex determination and early gonad development."
      Buaas F.W., Val P., Swain A.
      Hum. Mol. Genet. 18:2989-3001(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiWT1_MOUSE
    AccessioniPrimary (citable) accession number: P22561
    Secondary accession number(s): A2A402
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: October 1, 2014
    This is version 143 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Presence of the KTS motif hinders interactions between DNA and zinc-finger 4.By similarity

    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