WT1

Wilms tumor 1
	; PDB rendering based on 1xf7.
Available structures
PDB	1LU6, 1XF7, 2G7T, 2G7V, 2G7W, 2G7X, 2JP9, 2JPA, 2PRT, 3HPJ, 3MYJ
Identifiers
Symbols	WT1; AWT1; GUD; NPHS4; WAGR; WIT-2; WT33
External IDs	OMIM: 607102 MGI: 98968 HomoloGene: 11536 GeneCards: WT1 Gene
Gene Ontology
Molecular function	• sequence-specific DNA binding transcription factor activity; • sequence-specific DNA binding transcription factor activity; • RNA binding; • protein binding; • zinc ion binding; • sequence-specific DNA binding; • transcription regulatory region DNA binding; • metal ion binding; • C2H2 zinc finger domain binding;
Cellular component	• intracellular; • nucleus; • nucleoplasm; • nucleoplasm; • cytoplasm; • nuclear speck;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • vasculogenesis; • ureteric bud development; • branching involved in ureteric bud morphogenesis; • kidney development; • regulation of organ formation; • transcription, DNA-dependent; • transcription, DNA-dependent; • regulation of transcription, DNA-dependent; • regulation of transcription, DNA-dependent; • regulation of transcription from RNA polymerase II promoter; • induction of apoptosis; • germ cell development; • heart development; • sex determination; • negative regulation of cell proliferation; • RNA splicing; • male gonad development; • tissue development; • negative regulation of translation; • negative regulation of cell growth; • adrenal gland development; • male genitalia development; • epithelial cell differentiation; • glomerulus development; • glomerular basement membrane development; • camera-type eye development; • negative regulation of apoptosis; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • mesenchymal to epithelial transition; • visceral serous pericardium development; • cellular response to cAMP; • cellular response to gonadotropin stimulus; • glomerular visceral epithelial cell differentiation; • posterior mesonephric tubule development; • metanephric epithelium development; • metanephric S-shaped body morphogenesis; • negative regulation of metanephric glomerular mesangial cell proliferation; • positive regulation of male gonad development; • negative regulation of female gonad development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

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

[edit] Function

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 protein has been found to bind a host of cellular factors, e.g. p53, a known tumor suppressor.

[edit] Degradation

The serine protease HtrA2 binds to WT1 and it cleaves WT1 at multiple sites following the treatment with cytotoxic drugs.^[6]^[7]

[edit] Interactions

WT1 has been shown to interact with U2AF2,^[8] PAWR,^[9] UBE2I^[10] and WTAP.^[11]

[edit] 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.^[12]^[13]

[edit] Editing Type

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 consiting of 10 nucleotides before the editing site and four after the site.^[12]

[edit] Editing Site

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)^[12]

[edit] Regulation

Editing is tissue specific and developmentally regulated.Editing shown to be restricted in testis and kidney in the rat.^[12]

[edit] Conservation

Editing of this gene product has been found to occur in mice and rats as well as humans.^[12]^[14]

[edit] Effects of editing

[edit] Structure

Rna editing results in an alternative amino acid being translated.^[12] The changes in amino acid occur in a region identified as a domain involved in transcription activation function.^[15]

[edit] Function

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.^[14]

[edit] References

^ 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.
^ 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.
^ 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.
^ 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.
^ "Entrez Gene: WT1 Wilms tumor 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7490.
^ 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.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2815029.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317218.
^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231698.
^ 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.
^ 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. PMID 11001926.
^ ^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. PMID 7926762. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=7926762.
^ 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. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12665546.
^ ^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. http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=11065340.
^ 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. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=8486616.

[edit] 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.

[edit] External links

This article on a gene on chromosome 11 is a stub. You can help Wikipedia by expanding it.

[pmid2406020-0] 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.

[pmid2154335-1] 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.

[pmid2154702-2] 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.

[pmid2173145-3] 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.

[4] "Entrez Gene: WT1 Wilms tumor 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7490.

[pmid20122396-5] 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.

[pmid20122399-6] 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2815029.

[pmid9784496-7] 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317218.

[pmid8943350-8] 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231698.

[pmid8798754-9] 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.

[pmid11001926-10] 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. PMID 11001926.

[pmid7926762-11] ^ ^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. PMID 7926762. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=7926762.

[pmid12665546-12] 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. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12665546.

[pmid11065340-13] 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. http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=11065340.

[pmid8486616-14] 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. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=8486616.

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WT1

Contents

[edit] Function

[edit] Degradation

[edit] Interactions

[edit] Rna Editing

[edit] Editing Type

[edit] Editing Site

[edit] Regulation

[edit] Conservation

[edit] Effects of editing

[edit] Structure

[edit] Function

[edit] References

[edit] Further reading

[edit] External links

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