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P22561

- WT1_MOUSE

UniProt

P22561 - WT1_MOUSE

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Protein

Wilms tumor protein homolog

Gene

Wt1

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 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. RNA binding Source: MGI
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: UniProtKB
  5. sequence-specific DNA binding Source: UniProtKB
  6. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  7. transcription regulatory region DNA binding Source: UniProtKB
  8. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. adrenal cortex formation Source: UniProtKB
  2. adrenal gland development Source: UniProtKB
  3. apoptotic process Source: MGI
  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 apoptotic process 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, DNA-templated Source: UniProtKB
  40. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  41. posterior mesonephric tubule development Source: UniProtKB
  42. regulation of gene expression Source: MGI
  43. regulation of organ formation Source: UniProtKB
  44. regulation of transcription, DNA-templated Source: MGI
  45. regulation of transcription from RNA polymerase II promoter Source: MGI
  46. RNA splicing Source: UniProtKB
  47. seminiferous tubule development Source: MGI
  48. Sertoli cell development Source: MGI
  49. sex determination Source: MGI
  50. single fertilization Source: MGI
  51. spermatogenesis Source: MGI
  52. sperm motility Source: MGI
  53. thorax and anterior abdomen determination Source: UniProtKB
  54. tissue development Source: MGI
  55. ureteric bud development Source: UniProtKB
  56. vasculogenesis Source: MGI
  57. 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

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. nucleoplasm Source: UniProtKB
  4. 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 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 318-438.
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.
InParanoidiP22561.
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

        10         20         30         40         50
MGSDVRDLNA LLPAVSSLGG GGGGCGLPVS GARQWAPVLD FAPPGASAYG
60 70 80 90 100
SLGGPAPPPA PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTLHFSGQF
110 120 130 140 150
TGTAGACRYG PFGPPPPSQA SSGQARMFPN APYLPSCLES QPTIRNQGYS
160 170 180 190 200
TVTFDGAPSY GHTPSHHAAQ FPNHSFKHED PMGQQGSLGE QQYSVPPPVY
210 220 230 240 250
GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ MNLGATLKGM
260 270 280 290 300
AAGSSSSVKW TEGQSNHGIG YESENHTAPI LCGAQYRIHT HGVFRGIQDV
310 320 330 340 350
RRVSGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE
360 370 380 390 400
KPYQCDFKDC ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT
410 420 430 440
HTRTHTGKTS EKPFSCRWHS CQKKFARSDE LVRHHNMHQR NMTKLHVAL

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.Curated

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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 318-438.
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 P22561.
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: October 29, 2014
This is version 144 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