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P22561 (WT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Wilms tumor protein homolog
Gene names
Name:Wt1
Synonyms:Wt-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length449 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.9 Ref.10

Subunit structure

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. Ref.4 Ref.5 Ref.6 Ref.10 Ref.11

Subcellular location

Isoform 1: Nucleus speckle.

Isoform 4: Nucleusnucleoplasm Ref.5 Ref.8 Ref.9 Ref.11.

Nucleus. Nucleusnucleolus By similarity. Cytoplasm. Nucleus speckle. Note: Shuttles between nucleus and cytoplasm. Ref.5 Ref.8 Ref.9 Ref.11

Tissue specificity

Detected in neurons of the embryonic dorsal root ganglion and in Sertoli cells of the adult testis (at protein level). Detected in kidney. Ref.8

Developmental stage

Expressed in the coelomic epithelium and within some mesonephric tubules of the genital ridge at 10 dpc. Expressed during kidney development. Ref.10 Ref.12

Miscellaneous

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

Sequence similarities

Belongs to the EGR C2H2-type zinc-finger protein family.

Contains 4 C2H2-type zinc fingers.

RNA editing

Edited at position 281.
Partially edited By similarity.

Sequence caution

The sequence described in Ref.3 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative initiation
Alternative splicing
RNA editing
   DiseaseTumor suppressor
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
RNA-binding
Zinc
   PTMIsopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Inferred from direct assay Ref.4. Source: UniProtKB

adrenal cortex formation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

adrenal gland development

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

apoptotic DNA fragmentation

Inferred from sequence or structural similarity. Source: UniProtKB

branching involved in ureteric bud morphogenesis

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

camera-type eye development

Inferred from mutant phenotype PubMed 11889045PubMed 15716344. Source: MGI

cardiac muscle cell fate commitment

Inferred from mutant phenotype PubMed 21654746. Source: BHF-UCL

cellular response to cAMP

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular response to gonadotropin stimulus

Inferred from Biological aspect of Ancestor. Source: RefGenome

coronary vasculature development

Traceable author statement PubMed 20299672. Source: DFLAT

diaphragm development

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

epithelial cell differentiation

Inferred from mutant phenotype PubMed 9927198. Source: UniProtKB

germ cell development

Inferred from mutant phenotype PubMed 15063178. Source: MGI

glomerular visceral epithelial cell development

Inferred from expression pattern PubMed 18618131. Source: UniProtKB

glomerular visceral epithelial cell differentiation

Inferred from direct assay PubMed 19050011. Source: UniProtKB

glomerulus development

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

gonad development

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

heart development

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

kidney development

Inferred from mutant phenotype PubMed 11912180. Source: UniProtKB

male genitalia development

Inferred from mutant phenotype PubMed 10077614. Source: UniProtKB

male gonad development

Inferred from mutant phenotype PubMed 15063178. Source: MGI

mesenchymal to epithelial transition

Inferred from mutant phenotype PubMed 8395349PubMed 9927198. Source: UniProtKB

mesonephros development

Inferred from mutant phenotype PubMed 9118800. Source: MGI

metanephric S-shaped body morphogenesis

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

metanephric comma-shaped body morphogenesis

Inferred from expression pattern PubMed 18618131. Source: UniProtKB

metanephric mesenchyme development

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

metanephros development

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

negative regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of female gonad development

Inferred from mutant phenotype PubMed 19301398. Source: UniProtKB

negative regulation of mesenchymal cell apoptotic process involved in metanephros development

Inferred from mutant phenotype PubMed 8395349. Source: MGI

negative regulation of metanephric glomerular mesangial cell proliferation

Inferred from mutant phenotype PubMed 10077614. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence orthology PubMed 7585606. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 8530339. Source: UniProtKB

negative regulation of translation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of heart growth

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

positive regulation of male gonad development

Inferred from mutant phenotype PubMed 19301398. Source: UniProtKB

positive regulation of metanephric ureteric bud development

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16264195. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.10PubMed 8530339PubMed 9927198. Source: UniProtKB

posterior mesonephric tubule development

Inferred from mutant phenotype PubMed 9118800. Source: UniProtKB

regulation of organ formation

Inferred from mutant phenotype Ref.10. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12151099. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11889045. Source: MGI

sex determination

Inferred from mutant phenotype PubMed 11509181. Source: MGI

thorax and anterior abdomen determination

Inferred from mutant phenotype PubMed 8395349. Source: UniProtKB

tissue development

Inferred from mutant phenotype PubMed 15716344. Source: MGI

ureteric bud development

Inferred from mutant phenotype PubMed 10322633. Source: UniProtKB

vasculogenesis

Inferred from mutant phenotype PubMed 16264195. Source: MGI

visceral serous pericardium development

Inferred from mutant phenotype PubMed 10101119. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14678822Ref.5. Source: MGI

nuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 12609742PubMed 14701728Ref.8PubMed 19050011. Source: UniProtKB

   Molecular_functionC2H2 zinc finger domain binding

Inferred from sequence or structural similarity PubMed 8119964. Source: UniProtKB

RNA binding

Inferred from direct assay Ref.5. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 12609742PubMed 21719793. Source: UniProtKB

double-stranded DNA binding

Inferred from direct assay PubMed 7585606. Source: MGI

sequence-specific DNA binding

Inferred from sequence or structural similarity PubMed 8119964. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 8530339. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: P22561-1)

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.
Note: Detected in nucleus speckle, may bind mRNA.
Isoform 2 (identifier: P22561-2)

The sequence of this isoform differs from the canonical sequence as follows:
     250-266: Missing.
     408-410: Missing.
Isoform 3 (identifier: P22561-3)

The sequence of this isoform differs from the canonical sequence as follows:
     250-266: Missing.
Isoform 4 (identifier: P22561-4)

The sequence of this isoform differs from the canonical sequence as follows:
     408-410: Missing.
Note: Detected in nucleoplasm, probably functions as transcription factor.
Isoform 5 (identifier: P22561-5)

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.
Isoform 6 (identifier: P22561-6)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 449449Wilms tumor protein homolog
PRO_0000047132

Regions

Zinc finger323 – 34725C2H2-type 1
Zinc finger353 – 37725C2H2-type 2
Zinc finger383 – 40523C2H2-type 3
Zinc finger414 – 43825C2H2-type 4
Region367 – 38115Important for interaction with target DNA By similarity
Region393 – 4019Important for interaction with target DNA By similarity
Motif408 – 4103KTS motif By similarity
Compositional bias28 – 8356Pro-rich

Sites

Site4241Important for interaction with target DNA By similarity
Site4301Important for interaction with target DNA By similarity

Amino acid modifications

Cross-link73Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence11M → MDFLLSQEPASTCVPEPASQ HTLRREPGCVQQPEQPGDRG PRSAWAKSSAENPQDRRSGE PSASEPHLM in isoform 5 and isoform 6.
VSP_037585
Alternative sequence250 – 26617Missing in isoform 2, isoform 3 and isoform 6.
VSP_006868
Alternative sequence408 – 4103Missing in isoform 2 and isoform 4.
VSP_006869
Natural variant2811L → P in RNA edited version.

Experimental info

Sequence conflict331R → A in CAM18169. Ref.2
Sequence conflict2691I → T in CAM18169. Ref.2
Sequence conflict446 – 4472HV → QL in CAM18169. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 962381E9C8D7A380

FASTA44949,246
        10         20         30         40         50         60 
MGSDVRDLNA LLPAVSSLGG GGGGCGLPVS GARQWAPVLD FAPPGASAYG SLGGPAPPPA 

        70         80         90        100        110        120 
PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTLHFSGQF TGTAGACRYG PFGPPPPSQA 

       130        140        150        160        170        180 
SSGQARMFPN APYLPSCLES QPTIRNQGYS TVTFDGAPSY GHTPSHHAAQ FPNHSFKHED 

       190        200        210        220        230        240 
PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ 

       250        260        270        280        290        300 
MNLGATLKGM AAGSSSSVKW TEGQSNHGIG YESENHTAPI LCGAQYRIHT HGVFRGIQDV 

       310        320        330        340        350        360 
RRVSGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC 

       370        380        390        400        410        420 
ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT HTRTHTGKTS EKPFSCRWHS 

       430        440 
CQKKFARSDE LVRHHNMHQR NMTKLHVAL 

« Hide

Isoform 2 [UniParc].

Checksum: E53D995E5773F9AA
Show »

FASTA42947,221
Isoform 3 [UniParc].

Checksum: F10430FD2220373E
Show »

FASTA43247,537
Isoform 4 [UniParc].

Checksum: E1D76ECAE93FB51D
Show »

FASTA44648,930
Isoform 5 [UniParc].

Checksum: 1752F2E98A0983E4
Show »

FASTA51756,651
Isoform 6 [UniParc].

Checksum: BB0560BE625E4B4D
Show »

FASTA50054,943

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"A WT1 co-regulator controls podocyte phenotype by shuttling between adhesion structures and nucleus."
Srichai M.B., Konieczkowski M., Padiyar A., Konieczkowski D.J., Mukherjee A., Hayden P.S., Kamat S., El-Meanawy M.A., Khan S., Mundel P., Lee S.B., Bruggeman L.A., Schelling J.R., Sedor J.R.
J. Biol. Chem. 279:14398-14408(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55512 mRNA. Translation: AAA40573.1.
AL512584 Genomic DNA. Translation: CAM18169.2.
PIRA39692.
UniGeneMm.389339.

3D structure databases

ProteinModelPortalP22561.
SMRP22561. Positions 303-438.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204587. 2 interactions.
IntActP22561. 1 interaction.
MINTMINT-243493.

PTM databases

PhosphoSiteP22561.

Proteomic databases

PaxDbP22561.
PRIDEP22561.

Protocols and materials databases

DNASU22431.
StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:98968. Wt1.

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000230937.
HOVERGENHBG006960.
InParanoidA2A402.
PhylomeDBP22561.

Gene expression databases

CleanExMM_WT1.
GenevestigatorP22561.

Family and domain databases

Gene3D3.30.160.60. 4 hits.
InterProIPR017987. Wilms_tumour.
IPR000976. Wilms_tumour_N.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF02165. WT1. 1 hit.
PF00096. zf-C2H2. 1 hit.
[Graphical view]
PRINTSPR00049. WILMSTUMOUR.
SMARTSM00355. ZnF_C2H2. 4 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio302875.
PROP22561.
SOURCESearch...

Entry information

Entry nameWT1_MOUSE
AccessionPrimary (citable) accession number: P22561
Secondary accession number(s): A2A402
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot