ID:WT1_HUMAN DESCRIPTION: RecName: Full=Wilms tumor protein; AltName: Full=WT33; FUNCTION: Transcription factor that plays an important role in cellular development and cell survival. Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'. 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. SUBUNIT: Homodimer. Interacts with WTIP. Interacts with actively translating polysomes. Detected in nuclear ribonucleoprotein (mRNP) particles. Interacts with HNRNPU via the zinc-finger region. Interacts with U2AF2. Interacts with CITED2 (By similarity). Interacts with ZNF224 via the zinc-finger region. Interacts with WTAP and SRY. Interacts with FAM123B/WTX. Interacts with RBM4. SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Cytoplasm (By similarity). Note=Shuttles between nucleus and cytoplasm (By similarity). SUBCELLULAR LOCATION: Isoform 1: Nucleus speckle. SUBCELLULAR LOCATION: Isoform 4: Nucleus, nucleoplasm. TISSUE SPECIFICITY: Expressed in the kidney and a subset of hematopoietic cells. RNA EDITING: Modified_positions=281; Note=Partially edited. DISEASE: Defects in WT1 are the cause of Frasier syndrome (FS) [MIM:136680]. FS is characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant. DISEASE: Defects in WT1 are the cause of Wilms tumor 1 (WT1) [MIM:194070]. WT is an embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms. DISEASE: Defects in WT1 are the cause of Denys-Drash syndrome (DDS) [MIM:194080]. DDS is a typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic. DISEASE: Defects in WT1 are the cause of nephrotic syndrome type 4 (NPHS4) [MIM:256370]. A renal disease characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen. DISEASE: Defects in WT1 are a cause of Meacham syndrome (MEACHS) [MIM:608978]. Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. DISEASE: Note=A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1. DISEASE: Defects in WT1 may be a cause of mesothelioma malignant (MESOM) [MIM:156240]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. MISCELLANEOUS: Presence of the KTS motif hinders interactions between DNA and zinc-finger 4. SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein family. SIMILARITY: Contains 4 C2H2-type zinc fingers. SEQUENCE CAUTION: Sequence=AAB33443.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; Sequence=CAA35956.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAA35956.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon; Sequence=CAC39220.3; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAI95758.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAI95759.2; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/WT1ID78.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WT1"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/wt1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P19544
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003723 RNA binding GO:0005515 protein binding GO:0008270 zinc ion binding GO:0010385 double-stranded methylated DNA binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0044729 hemi-methylated DNA-binding GO:0046872 metal ion binding GO:0070742 C2H2 zinc finger domain binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001570 vasculogenesis GO:0001657 ureteric bud development GO:0001658 branching involved in ureteric bud morphogenesis GO:0001822 kidney development GO:0003156 regulation of animal organ formation GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0007281 germ cell development GO:0007356 thorax and anterior abdomen determination GO:0007507 heart development GO:0007530 sex determination GO:0008285 negative regulation of cell proliferation GO:0008380 RNA splicing GO:0008406 gonad development GO:0008584 male gonad development GO:0009888 tissue development GO:0017148 negative regulation of translation GO:0030308 negative regulation of cell growth GO:0030325 adrenal gland development GO:0030539 male genitalia development GO:0030855 epithelial cell differentiation GO:0032835 glomerulus development GO:0032836 glomerular basement membrane development GO:0035802 adrenal cortex formation GO:0043010 camera-type eye development GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0045892 negative regulation of transcription, DNA-templated GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0060231 mesenchymal to epithelial transition GO:0060421 positive regulation of heart growth GO:0060539 diaphragm development GO:0060923 cardiac muscle cell fate commitment GO:0061032 visceral serous pericardium development GO:0071320 cellular response to cAMP GO:0071371 cellular response to gonadotropin stimulus GO:0072075 metanephric mesenchyme development GO:0072112 glomerular visceral epithelial cell differentiation GO:0072166 posterior mesonephric tubule development GO:0072207 metanephric epithelium development GO:0072284 metanephric S-shaped body morphogenesis GO:0072302 negative regulation of metanephric glomerular mesangial cell proliferation GO:2000020 positive regulation of male gonad development GO:2000195 negative regulation of female gonad development GO:2001076 positive regulation of metanephric ureteric bud development
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
