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Wilms' tumor protein; WT1 protein (WT1, WT3)

Function: - role in cell survival & proliferation (putative) - role in transcriptional regulation (putative) - recognizes & binds to the DNA sequence 5'-CGCCCCCGC-3' - interacts with WTIP (putative) - interacts with ZNF224 via the Zn+2-finger region - interacts with WTAP & SRY - one isoform binds the amphiregulin promoter & activates transcription [3] - downstream regulated genes may also include those for nephrin, podocalyxin [4] & cyclin E [5] - WT1 functions in gonad formation & sex determination. - targets include sry, wnt4, dax1 & MIS. Structure: - belongs to the EGR C2H2-type Zn+2-finger protein family - contains 4 C2H2-type Zn+2 fingers Compartment: nucleus Alternative splicing: - named isoforms=5 - alternative splicing may give rise to transcription factors with different DNA-binding specificities. - exons 5 & 9 are alternatively spliced - exon 5 is mammal specific & contains a domain which permits association with prostate apoptosis factor 4 (par4). Exon 9 codes for a KTS sequence between the 3rd & 4th zinc finger. - forms containing the KTS sequence are denoted WT[+KTS], those without WT[-KTS]; the ratio of the two is nearly constant in all cell types [4] Expression: - expressed in kidney & a subset of hematopoietic cells - embryonic development: a) urogenital system b) spleen c) portions of brain & spinal cord - may play role in neuronal development d) mesothelial organs e) diaphragm f) proliferating coelomic epithelium g) epicardium & subepicardial mesenchyme - adult expression: a) kidney b) Sertoli cells in testes c) granulosa cells in ovaries Pathology: - defects in WT1 are the cause of a) Frasier syndrome b) genitourinary dysplasia component of WAGR syndrome c) Wilms tumor 1 d) Denys-Drash syndrome e) isolated diffuse mesangial sclerosis f) Meacham syndrome g) hypospadias - chromosomal translocation t(11;22)(p13;q12) involving WT1 with EWSR1 is associated with desmoplastic small round cell tumor (DSRCT) - expression associated with hypoxia/ischemia a) normally absent in adult heart b) re-expressed in smooth muscle & endothelial cells or coronary arteries after myocardial infarction or myocardial ischemia c) colocalizes with cell proliferation markers & VEGF - neoplasms (positive immunostaining) [5] - Wilms tumor/nephroblastoma - mesothelioma - AML - desmoplastic small round cell tumor of lung - metanephric adenoma - ovarian epithelial neoplasms - rhabdoid tumor

Related

Wilms tumor gene, WAGR gene or wt1 WT-1 Ag in tissue

General

C2H2 type zinc finger protein DNA-binding protein transcription factor (TF)

Properties

SIZE: entity length = 449 aa MW = 49 kD COMPARTMENT: cell nucleus MOTIF: proline-rich region SITE: 27-83 MOTIF: proline residue (SEVERAL) Zn finger C2H2-type SITE: 323-347 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 353-377 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 383-405 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 414-438 EFFECTOR-BOUND: Zn+2

Database Correlations

OMIM correlations MORBIDMAP 607102 UniProt P19544 PFAM correlations Entrez Gene 7490 Kegg hsa:7490

References

  1. Rauscher FJ et al Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science 250:1259 1990 PMID: 2244209
  2. Bickmore WA et al Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science 257:235 1992 PMID: 1321494
  3. Lee et al, The Wilms tumor suppressor WT1 encodes a transcriptional activator amphregulin. Cell 98:663-673, 1999 PMID: 10490105
  4. Wagner KD et al, The complex life of WT1 J Cell Science 116:1653-8, 2003 PMID: 12565546
  5. Loeb DM et al. Cyclin E is a target of WT1 transcriptional repression J Biol Chem 277(22):19627-32, 2002 PMID: 11919196
  6. Richard DJ, Schumacher V, Royer-Pokora B, Roberts SG. Genes & Development 15:328-39, 2001 PMID: 11159913 Free PMC Article
  7. http://pathologyoutlines.com/stains.html 18 May 2003
  8. Entrez Gene :accession 7490
  9. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/WT1ID78.html
  10. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=WT1
  11. UniProt :accession P19544