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P22561

- WT1_MOUSE

UniProt

P22561 - WT1_MOUSE

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Protein
Wilms tumor protein homolog
Gene
Wt1, Wt-1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 DNA By similarity
Sitei430 – 4301Important for interaction with target DNA By similarity

Regions

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

GO - Molecular functioni

  1. C2H2 zinc finger domain binding Source: UniProtKB
  2. RNA binding Source: MGI
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: UniProtKB
  4. double-stranded DNA binding Source: MGI
  5. protein binding 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. RNA splicing Source: UniProtKB
  2. adrenal cortex formation Source: UniProtKB
  3. adrenal gland development Source: UniProtKB
  4. apoptotic DNA fragmentation Source: UniProtKB
  5. branching involved in ureteric bud morphogenesis Source: UniProtKB
  6. camera-type eye development Source: MGI
  7. cardiac muscle cell fate commitment Source: BHF-UCL
  8. cellular response to cAMP Source: RefGenome
  9. cellular response to gonadotropin stimulus Source: UniProtKB
  10. coronary vasculature development Source: DFLAT
  11. diaphragm development Source: UniProtKB
  12. epithelial cell differentiation Source: UniProtKB
  13. germ cell development Source: MGI
  14. glomerular visceral epithelial cell development Source: UniProtKB
  15. glomerular visceral epithelial cell differentiation Source: UniProtKB
  16. glomerulus development Source: UniProtKB
  17. gonad development Source: UniProtKB
  18. heart development Source: UniProtKB
  19. kidney development Source: UniProtKB
  20. male genitalia development Source: UniProtKB
  21. male gonad development Source: MGI
  22. mesenchymal to epithelial transition Source: UniProtKB
  23. mesonephros development Source: MGI
  24. metanephric S-shaped body morphogenesis Source: UniProtKB
  25. metanephric comma-shaped body morphogenesis Source: UniProtKB
  26. metanephric mesenchyme development Source: UniProtKB
  27. metanephros development Source: UniProtKB
  28. negative regulation of apoptotic process Source: UniProtKB
  29. negative regulation of cell growth Source: UniProtKB
  30. negative regulation of female gonad development Source: UniProtKB
  31. negative regulation of mesenchymal cell apoptotic process involved in metanephros development Source: MGI
  32. negative regulation of metanephric glomerular mesangial cell proliferation Source: UniProtKB
  33. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  34. negative regulation of transcription, DNA-templated Source: UniProtKB
  35. negative regulation of translation Source: UniProtKB
  36. positive regulation of heart growth Source: UniProtKB
  37. positive regulation of male gonad development Source: UniProtKB
  38. positive regulation of metanephric ureteric bud development Source: UniProtKB
  39. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  40. positive regulation of transcription, DNA-templated Source: UniProtKB
  41. posterior mesonephric tubule development Source: UniProtKB
  42. regulation of organ formation Source: UniProtKB
  43. regulation of transcription from RNA polymerase II promoter Source: MGI
  44. regulation of transcription, DNA-templated Source: MGI
  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
Complete GO annotation...

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

Isoform 1 : Nucleus speckle 4 Publications
Isoform 4 : Nucleusnucleoplasm 4 Publications
Nucleus. Nucleusnucleolus By similarity. Cytoplasm. Nucleus speckle
Note: Shuttles between nucleus and cytoplasm.4 Publications

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
Complete GO annotation...

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 homolog
PRO_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 CITED2.5 Publications

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP22561.
SMRiP22561. Positions 293-438.

Family & Domainsi

Region

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

Motif

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

Compositional bias

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

Sequence similaritiesi

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.

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.
VSP_037585
Alternative sequencei250 – 26617Missing in isoform 2, isoform 3 and isoform 6.
VSP_006868Add
BLAST
Alternative sequencei408 – 4103Missing in isoform 2 and isoform 4.
VSP_006869

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti33 – 331R → A in CAM18169. 1 Publication
Sequence conflicti269 – 2691I → T in CAM18169. 1 Publication
Sequence conflicti446 – 4472HV → QL in CAM18169. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 142 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

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