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Protein

Wilms tumor protein homolog

Gene

Wt1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 (PubMed:16467207, PubMed:16920711, PubMed:17537799). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (By similarity). Regulates the expression of numerous target genes, including EPO (PubMed:16467207). Plays an essential role for development of the urogenital system. 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 (PubMed:17167543). Isoform 1 has lower affinity for DNA, and can bind RNA.By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei424Important for interaction with target DNABy similarity1
Sitei430Important for interaction with target DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri323 – 347C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri353 – 377C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri383 – 405C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri414 – 438C2H2-type 4PROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: UniProtKB
  • double-stranded DNA binding Source: MGI
  • double-stranded methylated DNA binding Source: UniProtKB
  • hemi-methylated DNA-binding Source: UniProtKB
  • RNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • adrenal cortex formation Source: UniProtKB
  • adrenal gland development Source: UniProtKB
  • apoptotic process Source: MGI
  • branching involved in ureteric bud morphogenesis Source: UniProtKB
  • camera-type eye development Source: MGI
  • cardiac muscle cell fate commitment Source: BHF-UCL
  • cellular response to gonadotropin stimulus Source: UniProtKB
  • coronary vasculature development Source: DFLAT
  • diaphragm development Source: UniProtKB
  • epithelial cell differentiation Source: UniProtKB
  • flagellated sperm motility Source: MGI
  • germ cell development Source: MGI
  • glomerular basement membrane development Source: MGI
  • glomerular visceral epithelial cell development Source: UniProtKB
  • glomerular visceral epithelial cell differentiation Source: UniProtKB
  • glomerulus development Source: UniProtKB
  • gonad development Source: UniProtKB
  • heart development Source: UniProtKB
  • kidney development Source: UniProtKB
  • male genitalia development Source: UniProtKB
  • male gonad development Source: MGI
  • mesenchymal to epithelial transition Source: UniProtKB
  • mesonephros development Source: MGI
  • metanephric comma-shaped body morphogenesis Source: UniProtKB
  • metanephric mesenchyme development Source: UniProtKB
  • metanephric S-shaped body morphogenesis Source: UniProtKB
  • metanephros development Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of female gonad development Source: UniProtKB
  • negative regulation of mesenchymal cell apoptotic process involved in metanephros development Source: MGI
  • negative regulation of metanephric glomerular mesangial cell proliferation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of translation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of heart growth Source: UniProtKB
  • positive regulation of male gonad development Source: UniProtKB
  • positive regulation of metanephric ureteric bud development Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • posterior mesonephric tubule development Source: UniProtKB
  • regulation of animal organ formation Source: UniProtKB
  • regulation of gene expression Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • RNA splicing Source: UniProtKB
  • seminiferous tubule development Source: MGI
  • Sertoli cell development Source: MGI
  • sex determination Source: MGI
  • single fertilization Source: MGI
  • spermatogenesis Source: MGI
  • thorax and anterior abdomen determination Source: UniProtKB
  • tissue development Source: MGI
  • ureteric bud development Source: UniProtKB
  • vasculogenesis Source: MGI
  • 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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:98968. Wt1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nuclear speck Source: UniProtKB
  • nucleolus Source: UniProtKB-SubCell
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000471321 – 449Wilms tumor protein homologAdd BLAST449

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki73Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiP22561.
PRIDEiP22561.

PTM databases

PhosphoSitePlusiP22561.

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.

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

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: UniProtKB

Protein-protein interaction databases

IntActiP22561. 1 interactor.
MINTiMINT-243493.
STRINGi10090.ENSMUSP00000117891.

Structurei

3D structure databases

ProteinModelPortaliP22561.
SMRiP22561.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni367 – 381Important for interaction with target DNABy similarityAdd BLAST15
Regioni393 – 401Important for interaction with target DNABy similarity9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi408 – 410KTS motifBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi28 – 83Pro-richAdd BLAST56

Domaini

Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine.By similarity

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri323 – 347C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri353 – 377C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri383 – 405C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri414 – 438C2H2-type 4PROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
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. 2 hits.
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. AlignAdd to basket

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 PubMed:8621495 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33R → A in CAM18169 (PubMed:19468303).Curated1
Sequence conflicti269I → T in CAM18169 (PubMed:19468303).Curated1
Sequence conflicti446 – 447HV → QL in CAM18169 (PubMed:19468303).Curated2

RNA editingi

Edited at position 281.By similarity
Partially edited.By similarity

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti281L → P in RNA edited version. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0375851M → MDFLLSQEPASTCVPEPASQ HTLRREPGCVQQPEQPGDRG PRSAWAKSSAENPQDRRSGE PSASEPHLM in isoform 5 and isoform 6. Curated1
Alternative sequenceiVSP_006868250 – 266Missing in isoform 2, isoform 3 and isoform 6. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_006869408 – 410Missing in isoform 2 and isoform 4. 1 Publication3

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.
CCDSiCCDS16496.2. [P22561-5]
PIRiA39692.
UniGeneiMm.389339.

3D structure databases

ProteinModelPortaliP22561.
SMRiP22561.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP22561. 1 interactor.
MINTiMINT-243493.
STRINGi10090.ENSMUSP00000117891.

PTM databases

PhosphoSitePlusiP22561.

Proteomic databases

PaxDbiP22561.
PRIDEiP22561.

Protocols and materials databases

DNASUi22431.
Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:98968. Wt1.

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
HOGENOMiHOG000230937.
HOVERGENiHBG006960.
InParanoidiP22561.
PhylomeDBiP22561.

Miscellaneous databases

PROiP22561.
SOURCEiSearch...

Gene expression databases

CleanExiMM_WT1.

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. 2 hits.
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]
ProtoNetiSearch...

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: November 2, 2016
This is version 157 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

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 one 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.