InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: WT1

Summary

InnateDB Protein

IDBP-37986.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

WT1

Protein Name

Wilms tumor 1

Synonyms

AWT1; EWS-WT1; GUD; NPHS4; WAGR; WIT-2; WT33;

Species

Homo sapiens

Ensembl Protein

ENSP00000368370

InnateDB Gene

IDBG-37982 (WT1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:19123921, ECO:0000269PubMed:19416806}.

Subcellular Localization

Nucleus. Nucleus, nucleolus. Cytoplasm {ECO:0000250}. Note=Shuttles between nucleus and cytoplasm. {ECO:0000250}.Isoform 1: Nucleus speckle.Isoform 4: Nucleus, nucleoplasm.

Disease Associations

Frasier syndrome (FS) [MIM:136680]: 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. {ECO:0000269PubMed:10571943}. Note=The disease is caused by mutations affecting the gene represented in this entry.Wilms tumor 1 (WT1) [MIM:194070]: Embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms. {ECO:0000269PubMed:1317572, ECO:0000269PubMed:15150775, ECO:0000269PubMed:9108089, ECO:0000269PubMed:9529364}. Note=The disease is caused by mutations affecting the gene represented in this entry.Denys-Drash syndrome (DDS) [MIM:194080]: 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. {ECO:0000269PubMed:10738002, ECO:0000269PubMed:10799199, ECO:0000269PubMed:11182928, ECO:0000269PubMed:11519891, ECO:0000269PubMed:1302008, ECO:0000269PubMed:1338906, ECO:0000269PubMed:15349765, ECO:0000269PubMed:1655284, ECO:0000269PubMed:8111391, ECO:0000269PubMed:8112732, ECO:0000269PubMed:8295405, ECO:0000269PubMed:8388765, ECO:0000269PubMed:8411073, ECO:0000269PubMed:8741319, ECO:0000269PubMed:8956030, ECO:0000269PubMed:9475094, ECO:0000269PubMed:9529364}. Note=The disease is caused by mutations affecting the gene represented in this entry.Nephrotic syndrome 4 (NPHS4) [MIM:256370]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as 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. {ECO:0000269PubMed:11182928, ECO:0000269PubMed:15253707, ECO:0000269PubMed:9529364, ECO:0000269PubMed:9607189}. Note=The disease is caused by mutations affecting the gene represented in this entry.Meacham syndrome (MEACHS) [MIM:608978]: 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. {ECO:0000269PubMed:17853480}. Note=The disease is caused by mutations affecting the gene represented in this entry.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.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. {ECO:0000269PubMed:8401592}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in the kidney and a subset of hematopoietic cells.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	29 [view]
Protein-Protein	27 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003723	RNA binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region 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 organ formation
GO:0006309	apoptotic DNA fragmentation
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of 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: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