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6  structures 53  species 0  interactions 147  sequences 10  architectures

Family: WT1 (PF02165)

Summary: Wilm's tumour protein

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WT1 Edit Wikipedia article

Symbol WT1
Pfam PF02165
InterPro IPR000976
Wilms tumor 1
Protein WT1 PDB 1xf7.png
PDB rendering based on 1xf7.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols WT1 ; AWT1; EWS-WT1; GUD; NPHS4; WAGR; WIT-2; WT33
External IDs OMIM607102 MGI98968 HomoloGene11536 GeneCards: WT1 Gene
RNA expression pattern
PBB GE WT1 206067 s at tn.png
PBB GE WT1 216953 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7490 22431
Ensembl ENSG00000184937 ENSMUSG00000016458
UniProt P19544 P22561
RefSeq (mRNA) NM_000378 NM_144783
RefSeq (protein) NP_000369 NP_659032
Location (UCSC) Chr 11:
32.41 – 32.46 Mb
Chr 2:
105.13 – 105.17 Mb
PubMed search [1] [2]

Wilms tumor protein is a protein that in humans is encoded by the WT1 gene on chromosome 11p.[1][2][3][4]


This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms' tumor, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.[5]


The WT1 gene product shows similarity to the zinc fingers of the mammalian growth regulated early growth response protein 1 (EGR1) and (EGR2) proteins.[6]

Clinical significance

Wilm's tumour tumor suppressor gene1 (WT1) causes is an embryonic malignancy of the kidney, affecting around 1 in 10,000 infants. It occurs in both sporadic and hereditary forms. Inactivation of WT1 causes Wilm's tumour, and Denys-Drash syndrome (DDS), leading to nephropathy and genital abnormalities. The WT1 protein has been found to bind a host of cellular factors, e.g. p53, a known tumor suppressor.[3][7][8][9]

The serine protease HtrA2 binds to WT1 and it cleaves WT1 at multiple sites following the treatment with cytotoxic drugs.[10][11]

Using immunohistochemistry, WT1 protein can be demonstrated in the cell nuclei of 75% of mesotheliomas and in 93% of ovarian serous carcinomas, as well as in benign mesothelium and fallopian tube epithelium. This allows these tumours to be distinguished from other, similar, cancers, such as adenocarcinoma. Antibodies to the WT1 protein, however, also frequently cross-react with cytoplasmic proteins in a variety of benign and malignant cells, so that only nuclear staining can be considered diagnostic.[12]


WT1 has been shown to interact with U2AF2,[13] PAWR,[14] UBE2I[15] and WTAP.[16]

RNA editing

There is some evidence for RNA editing of human WT1 mRNA.As with alternative splicing of the gene RNA editing increases the number of isoforms of this protein.[17][18]

Editing is tissue specific and developmentally regulated. Editing shown to be restricted in testis and kidney in the rat.[17] Editing of this gene product has been found to occur in mice and rats as well as humans.[17][19]

Editing type

The editing site is found at nucleotide position 839 found in exon 6 of the gene.It causes a codon change from a Proline codon (CCC) to a Leucine codon (CUC)[17]

The type of editing is a Uridine to Cytidine( U to C) base change .The editing reaction is thought to be an amidation of uridine which converts it to a Cytidine.The relevance of this editing is unknown as is the enzyme responsible for this editing.The region where editing occurs like that of other editing sites e.g. ApoB mRNA editing is conserved.Mice, rat and humans have conserved sequences flanking the editing site consisting of 10 nucleotides before the editing site and four after the site.[17]

Effects of editing

RNA editing results in an alternative amino acid being translated.[17] The changes in amino acid occur in a region identified as a domain involved in transcription activation function.[20]

Editing has been shown to decrease repressive regulation of transcription of growth promoting genes in vitro compared to the non edited protein. Although the physiological role of editing has yet to be determined, suggestions have been made that editing may play a role in the pathogenesis of Wilms tumour.[19]


  1. ^ Burgin AB, Parodos K, Lane DJ, Pace NR (February 1990). "The excision of intervening sequences from Salmonella 23S ribosomal RNA". Cell 60 (3): 405–14. doi:10.1016/0092-8674(90)90592-3. PMID 2406020. 
  2. ^ Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH (February 1990). "Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus". Cell 60 (3): 509–20. doi:10.1016/0092-8674(90)90601-A. PMID 2154335. 
  3. ^ a b Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA (February 1990). "Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping". Nature 343 (6260): 774–8. doi:10.1038/343774a0. PMID 2154702. 
  4. ^ Huang A, Campbell CE, Bonetta L, McAndrews-Hill MS, Chilton-MacNeill S, Coppes MJ, Law DJ, Feinberg AP, Yeger H, Williams BR (November 1990). "Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor". Science 250 (4983): 991–4. doi:10.1126/science.2173145. PMID 2173145. 
  5. ^ "Entrez Gene: WT1 Wilms tumor 1". 
  6. ^ Han Y, San-Marina S, Yang L, Khoury H, Minden MD (2007). "The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells.". Breast Cancer Res 9 (4): R43. doi:10.1186/bcr1743. PMC 2206716. PMID 17634147. 
  7. ^ Rauscher FJ (July 1993). "The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor". FASEB J. 7 (10): 896–903. PMID 8393820. 
  8. ^ Buckler AJ, Pelletier J, Haber DA, Glaser T, Housman DE (March 1991). "Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development". Mol. Cell. Biol. 11 (3): 1707–12. PMC 369476. PMID 1671709. 
  9. ^ Little MH, Prosser J, Condie A, Smith PJ, Van Heyningen V, Hastie ND (June 1992). "Zinc finger point mutations within the WT1 gene in Wilms tumor patients". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4791–5. doi:10.1073/pnas.89.11.4791. PMC 49173. PMID 1317572. 
  10. ^ Essafi A, Hastie ND (January 2010). "WT1 the oncogene: a tale of death and HtrA". Mol. Cell 37 (2): 153–5. doi:10.1016/j.molcel.2010.01.010. PMID 20122396. 
  11. ^ Hartkamp J, Carpenter B, Roberts SG (January 2010). "The Wilms' tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi". Mol. Cell 37 (2): 159–71. doi:10.1016/j.molcel.2009.12.023. PMC 2815029. PMID 20122399. 
  12. ^ Leong AS-Y, Cooper K, Leong FJW-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 447–448. ISBN 1-84110-100-1. 
  13. ^ Davies RC, Calvio C, Bratt E, Larsson SH, Lamond AI, Hastie ND (October 1998). "WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes". Genes Dev. 12 (20): 3217–25. doi:10.1101/gad.12.20.3217. PMC 317218. PMID 9784496. 
  14. ^ Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y (December 1996). "A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1". Mol. Cell. Biol. 16 (12): 6945–56. PMC 231698. PMID 8943350. 
  15. ^ Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF (October 1996). "Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9". J. Biol. Chem. 271 (40): 24811–6. doi:10.1074/jbc.271.40.24811. PMID 8798754. 
  16. ^ Little NA, Hastie ND, Davies RC (September 2000). "Identification of WTAP, a novel Wilms' tumour 1-associating protein". Hum. Mol. Genet. 9 (15): 2231–9. doi:10.1093/oxfordjournals.hmg.a018914. PMID 11001926. 
  17. ^ a b c d e f Sharma PM, Bowman M, Madden SL, Rauscher FJ, Sukumar S (March 1994). "RNA editing in the Wilms' tumor susceptibility gene, WT1". Genes Dev. 8 (6): 720–31. doi:10.1101/gad.8.6.720. PMID 7926762. 
  18. ^ Wagner KD, Wagner N, Schedl A (May 2003). "The complex life of WT1". J. Cell. Sci. 116 (Pt 9): 1653–8. doi:10.1242/jcs.00405. PMID 12665546. 
  19. ^ a b Mrowka C, Schedl A (November 2000). "Wilms' tumor suppressor gene WT1: from structure to renal pathophysiologic features". J. Am. Soc. Nephrol. 11 Suppl 16: S106–15. PMID 11065340. 
  20. ^ Wang ZY, Qiu QQ, Deuel TF (May 1993). "The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains". J. Biol. Chem. 268 (13): 9172–5. PMID 8486616. 

Further reading

  • Haber DA, Buckler AJ (1992). "WT1: a novel tumor suppressor gene inactivated in Wilms' tumor.". New Biol. 4 (2): 97–106. PMID 1313285. 
  • Rauscher FJ (1993). "The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor.". FASEB J. 7 (10): 896–903. PMID 8393820. 
  • Lee SB, Haber DA (2001). "Wilms tumor and the WT1 gene.". Exp. Cell Res. 264 (1): 74–99. doi:10.1006/excr.2000.5131. PMID 11237525. 
  • Scharnhorst V, van der Eb AJ, Jochemsen AG (2001). "WT1 proteins: functions in growth and differentiation.". Gene 273 (2): 141–61. doi:10.1016/S0378-1119(01)00593-5. PMID 11595161. 
  • Lim HN, Hughes IA, Hawkins JR (2003). "Clinical and molecular evidence for the role of androgens and WT1 in testis descent.". Mol. Cell. Endocrinol. 185 (1–2): 43–50. doi:10.1016/S0303-7207(01)00631-1. PMID 11738793. 
  • Heathcott RW, Morison IM, Gubler MC, et al. (2002). "A review of the phenotypic variation due to the Denys-Drash syndrome-associated germline WT1 mutation R362X". Hum. Mutat. 19 (4): 462. doi:10.1002/humu.9031. PMID 11933209. 
  • Wagner KD, Wagner N, Schedl A (2004). "The complex life of WT1". J. Cell. Sci. 116 (Pt 9): 1653–8. doi:10.1242/jcs.00405. PMID 12665546. 
  • Amini Nik S, Hohenstein P (2005). "Upregulation of Wilms' tumor gene 1 (WT1) in desmoid tumors". Int J Cancer 114 (2): 202–8. doi:10.1002/ijc.20717. PMID 15540161. 
  • Niaudet P, Gubler MC (2007). "WT1 and glomerular diseases". Pediatr. Nephrol. 21 (11): 1653–60. doi:10.1007/s00467-006-0208-1. PMID 16927106. 
  • Coosemans A, Amini Nik S (2007). "Upregulation of Wilms' tumour gene 1 (WT1) in uterine sarcomas". Eur J Cancer 43 (10): 1630–37. doi:10.1016/j.ejca.2007.04.008. PMID 17531467. 
  • Hohenstein P, Hastie ND (2006). "The many facets of the Wilms' tumour gene, WT1". Hum. Mol. Genet. 15 Spec No 2: R196–201. doi:10.1093/hmg/ddl196. PMID 16987884. 

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Wilm's tumour protein Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000976

Wilm's tumour (WT) is an embryonal malignancy of the kidney, affecting around 1 in 10,000 infants. It occurs in both sporadic and hereditary forms. Inactivation of WT1 is one of the causes of Wilm's tumour. Defects in the WT1 gene are also associated with Denys-Drash Syndrome (DDS), which is characterised by typical nephropathy and genital abnormalities. The WT1 gene product shows similarity to the zinc fingers of the mammalian growth regulated EGR1 and EGR2 proteins [PUBMED:8393820, PUBMED:1671709, PUBMED:2154702, PUBMED:1317572].

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Seed source: IPR000976
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 8
Number in full: 147
Average length of the domain: 217.70 aa
Average identity of full alignment: 64 %
Average coverage of the sequence by the domain: 67.01 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.6 19.6
Trusted cut-off 21.8 20.5
Noise cut-off 16.9 16.8
Model length: 293
Family (HMM) version: 10
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Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the WT1 domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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