Wilms tumor protein

Function

Transcription factor that plays an important role in cellular development and cell survival. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'. Regulates the expression of numerous target genes, including EPO. 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. Isoform 1 has lower affinity for DNA, and can bind RNA.

Classification

Family (Pfam)

PF02165 WT1, PF00096 zf-C2H2

InterPro

Wilms_tumour_N, Znf_C2H2_sf, Znf_C2H2_type

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 27

• 1XF7 NMR
• 2JP9 NMR
• 2JPA NMR
• 2PRT X-ray 3.15A
• 3HPJ X-ray 2.00A
• 3MYJ X-ray 1.89A
• 4R2E X-ray 1.84A
• 4R2P X-ray 1.79A
• 4R2Q X-ray 1.54A
• 4R2R X-ray 2.09A
• 4R2S X-ray 2.49A
• 4WUU X-ray 3.05A
• … and 15 more

A predicted model is available from AlphaFold.

Gene Ontology · 68

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0016607 nuclear speck
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0070742 C2H2 zinc finger domain binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0010385 double-stranded methylated DNA binding
• GO:0044729 hemi-methylated DNA-binding
• GO:0003723 RNA binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0043565 sequence-specific DNA binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0008270 zinc ion binding
• GO:0035802 adrenal cortex formation
• GO:0030325 adrenal gland development
• GO:0001658 branching involved in ureteric bud morphogenesis
• GO:0043010 camera-type eye development
• GO:0060923 cardiac muscle cell fate commitment
• GO:0071320 cellular response to cAMP
• GO:0071371 cellular response to gonadotropin stimulus
• GO:0060539 diaphragm development
• GO:0006351 DNA-templated transcription
• GO:0030855 epithelial cell differentiation
• GO:0007281 germ cell development
• GO:0032836 glomerular basement membrane development
• GO:0032835 glomerulus development
• GO:0008406 gonad development
• GO:0007507 heart development
• GO:0001822 kidney development
• GO:0030539 male genitalia development
• GO:0008584 male gonad development
• GO:0060231 mesenchymal to epithelial transition
• GO:0072207 metanephric epithelium development
• GO:0072075 metanephric mesenchyme development
• GO:0072284 metanephric S-shaped body morphogenesis
• GO:0043066 negative regulation of apoptotic process
• GO:0030308 negative regulation of cell growth
• GO:0008285 negative regulation of cell population proliferation
• GO:0045892 negative regulation of DNA-templated transcription
• GO:2000195 negative regulation of female gonad development
• GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
• GO:0072302 negative regulation of metanephric glomerular mesangial cell proliferation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0017148 negative regulation of translation
• GO:0072112 podocyte differentiation
• GO:0043065 positive regulation of apoptotic process
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0010628 positive regulation of gene expression
• GO:0060421 positive regulation of heart growth
• GO:2000020 positive regulation of male gonad development
• GO:2001076 positive regulation of metanephric ureteric bud development
• GO:1902895 positive regulation of miRNA transcription
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0072166 posterior mesonephric tubule development
• GO:0003156 regulation of animal organ formation
• GO:0006355 regulation of DNA-templated transcription
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0008380 RNA splicing
• GO:0007530 sex determination
• GO:0007356 thorax and anterior abdomen determination
• GO:0009888 tissue development
• GO:0001657 ureteric bud development
• GO:0001570 vasculogenesis
• GO:0061032 visceral serous pericardium development

Disease associations

• Frasier syndrome MONDO:0007635
• malignant mesothelioma MONDO:0006292
• Wilms tumor 1 MONDO:0008679
• Denys-Drash syndrome MONDO:0008682
• nephrotic syndrome, type 4 MONDO:0009733
• Meacham syndrome MONDO:0012164

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Wilms tumor protein homolog 0.99
• Wilms tumor protein homolog 0.99
• Wilms tumor protein homolog 0.99
• Wilms tumor protein homolog 0.88
• Krueppel-like factor 4 0.86
• Zinc finger protein GLIS3 0.86
• Transcription activator GLI1 0.86
• Wilms tumor protein homolog A 0.84
• Krueppel-like factor 4 0.84
• Transcription activator GLI1 0.82
• Zinc finger protein ZIC 4 0.82
• Transcription activator GLI1 0.81

Co-cited proteins · studied together in the literature

• Wilms tumor protein homolog 1 shared papers
• Wilms tumor protein homolog 2 shared papers
• Early growth response protein 1 1 shared papers
• APC membrane recruitment protein 1 1 shared papers
• Zinc finger protein 224 1 shared papers
• RNA-binding protein 4 1 shared papers
• Sex-determining region Y protein 1 shared papers
• Pre-mRNA-splicing regulator WTAP 1 shared papers
• Laminin subunit beta-2 1 shared papers
• Pre-mRNA-splicing regulator WTAP 1 shared papers
• Podocin 1 shared papers
• Short transient receptor potential channel 6 1 shared papers

Literature · 54 cited papers

• The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs. Cell. Mol. Life Sci. · 2020
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence. Genes Dev. · 2014
• Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin. J. Am. Soc. Nephrol. · 2010
• The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Contribution of individual amino acids to the RNA binding activity of the Wilms' tumor suppressor protein WT1. Biochemistry · 2009
• WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. Am. J. Med. Genet. A · 2007
• Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA. J. Mol. Biol. · 2007
• A tumor suppressor and oncogene: the WT1 story. Leukemia · 2007
• WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo. Exp. Cell Res. · 2006
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• SUMO-1 modification of the Wilms' tumor suppressor WT1. Cancer Res. · 2004
• … and 42 more in the literature graph