SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000640 
UniProt Accession
Theoretical PI
9.23  
Molecular Weight
49188 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
WT1 
Gene Synonyms/Alias
 
Protein Name
Wilms tumor protein 
Protein Synonyms/Alias
WT33; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:11;32409321-32457176;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
The data presented here show that critical levels of WT1 + KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. 
The information of related literatures
1. V. Schumacher, B. Gueler, L. H. Looijenga, J. U. Becker, K. Amann, R. Engers, J. Dotsch, H. Stoop, W. Schulz and B. Royer-Pokora (2008) Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. Mol Reprod Dev 75(9): 1484-94. 

Abstract
Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1 + KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial-spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as 'testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1 + KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. PMID: [18271004] 

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Figures for illustrating the function of this protein/gene
Function
Transcription factor that plays an important role incellular development and cell survival. Regulates the expressionof numerous target genes, including EPO. Plays an essential rolefor development of the urogenital system. Recognizes and binds tothe DNA sequence 5'-CGCCCCCGC-3'. It has a tumor suppressor aswell as an oncogenic role in tumor formation. Function may beisoform-specific: isoforms lacking the KTS motif may act astranscription factors. Isoforms containing the KTS motif may bindmRNA and play a role in mRNA metabolism or splicing. Isoform 1 haslower affinity for DNA, and can bind RNA. 
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Subcellular Location
Isoform 4: Nucleus, nucleoplasm. 
Tissue Specificity
Expressed in the kidney and a subset ofhematopoietic cells. 
Gene Ontology
GO IDGO termEvidence
GO:0005737 C:cytoplasm ISS:UniProtKB.
GO:0016607 C:nuclear speck IDA:UniProtKB.
GO:0005730 C:nucleolus IEA:UniProtKB-SubCell.
GO:0005654 C:nucleoplasm IDA:UniProtKB.
GO:0003690 F:double-stranded DNA binding IEA:Compara.
GO:0003723 F:RNA binding IEA:UniProtKB-KW.
GO:0001077 F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription ISS:UniProtKB.
GO:0043565 F:sequence-specific DNA binding IDA:UniProtKB.
GO:0044212 F:transcription regulatory region DNA binding IDA:UniProtKB.
GO:0008270 F:zinc ion binding IDA:UniProtKB.
GO:0035802 P:adrenal cortex formation ISS:UniProtKB.
GO:0001658 P:branching involved in ureteric bud morphogenesis IGI:UniProtKB.
GO:0043010 P:camera-type eye development ISS:UniProtKB.
GO:0060923 P:cardiac muscle cell fate commitment ISS:BHF-UCL.
GO:0071320 P:cellular response to cAMP IEP:UniProtKB.
GO:0071371 P:cellular response to gonadotropin stimulus IDA:UniProtKB.
GO:0060539 P:diaphragm development ISS:UniProtKB.
GO:0007281 P:germ cell development ISS:UniProtKB.
GO:0032836 P:glomerular basement membrane development IMP:UniProtKB.
GO:0072112 P:glomerular visceral epithelial cell differentiation ISS:UniProtKB.
GO:0006917 P:induction of apoptosis IDA:UniProtKB.
GO:0030539 P:male genitalia development ISS:UniProtKB.
GO:0008584 P:male gonad development IEP:UniProtKB.
GO:0060231 P:mesenchymal to epithelial transition ISS:UniProtKB.
GO:0072207 P:metanephric epithelium development IEP:UniProtKB.
GO:0072075 P:metanephric mesenchyme development ISS:UniProtKB.
GO:0072284 P:metanephric S-shaped body morphogenesis IGI:UniProtKB.
GO:0043066 P:negative regulation of apoptotic process IGI:UniProtKB.
GO:0030308 P:negative regulation of cell growth IDA:UniProtKB.
GO:2000195 P:negative regulation of female gonad development ISS:UniProtKB.
GO:0072302 P:negative regulation of metanephric glomerular mesangial cell proliferation ISS:UniProtKB.
GO:0000122 P:negative regulation of transcription from RNA polymerase II promoter IDA:MGI.
GO:0045892 P:negative regulation of transcription, DNA-dependent IDA:UniProtKB.
GO:0017148 P:negative regulation of translation IDA:UniProtKB.
GO:0060421 P:positive regulation of heart growth ISS:UniProtKB.
GO:2000020 P:positive regulation of male gonad development ISS:UniProtKB.
GO:2001076 P:positive regulation of metanephric ureteric bud development ISS:UniProtKB.
GO:0045893 P:positive regulation of transcription, DNA-dependent IDA:UniProtKB.
GO:0072166 P:posterior mesonephric tubule development ISS:UniProtKB.
GO:0003156 P:regulation of organ formation ISS:UniProtKB.
GO:0008380 P:RNA splicing ISS:UniProtKB.
GO:0007530 P:sex determination IDA:UniProtKB.
GO:0007356 P:thorax and anterior abdomen determination ISS:UniProtKB.
GO:0001570 P:vasculogenesis ISS:UniProtKB.
GO:0061032 P:visceral serous pericardium development IGI:UniProtKB.
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Interpro
IPR017987;    Wilms_tumour.
IPR000976;    Wilms_tumour_N.
IPR007087;    Znf_C2H2.
IPR015880;    Znf_C2H2-like.
IPR013087;    Znf_C2H2/integrase_DNA-bd.
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Pfam
PF02165;    WT1;    1.
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SMART
SM00355;    ZnF_C2H2;    4.
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PROSITE
PS00028;    ZINC_FINGER_C2H2_1;    4.
PS50157;    ZINC_FINGER_C2H2_2;    4.
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PRINTS
PR00049;    WILMSTUMOUR.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    449       Wilms tumor protein.
                             /FTId=PRO_0000047131.
ZN_FING     323    347       C2H2-type 1.
ZN_FING     353    377       C2H2-type 2.
ZN_FING     383    405       C2H2-type 3.
ZN_FING     414    438       C2H2-type 4.
REGION      367    381       Important for interaction with target
                             DNA.
REGION      393    401       Important for interaction with target
                             DNA.
MOTIF       408    410       KTS motif.
COMPBIAS     27     83       Pro-rich.
SITE        424    424       Important for interaction with target
                             DNA.
SITE        430    430       Important for interaction with target
                             DNA.
CROSSLNK     73     73       Glycyl lysine isopeptide (Lys-Gly)
                             (interchain with G-Cter in SUMO).
CROSSLNK    177    177       Glycyl lysine isopeptide (Lys-Gly)
                             (interchain with G-Cter in SUMO).
VAR_SEQ       1    144       Missing (in isoform 6 and isoform 9).
                             /FTId=VSP_037582.
VAR_SEQ       1      1       M -> MDFLLLQDPASTCVPEPASQHTLRSGPGCLQQPEQQ
                             GVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQM
                             (in isoform 7 and isoform 8).
                             /FTId=VSP_037583.
VAR_SEQ     145    147       RNQ -> MEK (in isoform 6 and isoform 9).
                             /FTId=VSP_037584.
VAR_SEQ     250    266       Missing (in isoform 2, isoform 3, isoform
                             8 and isoform 9).
                             /FTId=VSP_006866.
VAR_SEQ     408    410       Missing (in isoform 2, isoform 4 and
                             isoform 6).
                             /FTId=VSP_006867.
VARIANT     131    131       A -> T (in a patient with hypospadias).
                             /FTId=VAR_043798.
VARIANT     181    181       P -> S (in WT1; dbSNP:rs2234584).
                             /FTId=VAR_007739.
VARIANT     223    223       S -> N (in WT1).
                             /FTId=VAR_007740.
VARIANT     253    253       G -> A (in WT1).
                             /FTId=VAR_007741.
VARIANT     273    273       S -> G (found in a mesothelioma sample;
                             somatic mutation; dbSNP:rs121907908).
                             /FTId=VAR_007742.
VARIANT     281    281       L -> P (in RNA edited version).
                             /FTId=VAR_058021.
VARIANT     312    312       R -> Q (in NPHS4).
                             /FTId=VAR_015053.
VARIANT     330    330       C -> Y (in DDS).
                             /FTId=VAR_007743.
VARIANT     342    342       M -> R (in DDS).
                             /FTId=VAR_015054.
VARIANT     355    355       C -> G (in WT1).
                             /FTId=VAR_043799.
VARIANT     355    355       C -> Y (in DDS).
                             /FTId=VAR_015055.
VARIANT     360    360       C -> G (in DDS).
                             /FTId=VAR_007744.
VARIANT     360    360       C -> Y (in DDS).
                             /FTId=VAR_043800.
VARIANT     364    364       F -> L (in NPHS4).
                             /FTId=VAR_043801.
VARIANT     366    366       R -> C (in WT1, DDS and MEACHS).
                             /FTId=VAR_007745.
VARIANT     366    366       R -> H (in DDS and WT1).
                             /FTId=VAR_007746.
VARIANT     366    366       R -> L (in DDS).
                             /FTId=VAR_043802.
VARIANT     369    369       Q -> P (in DDS).
                             /FTId=VAR_043803.
VARIANT     373    373       H -> Q (in DDS and WT1).
                             /FTId=VAR_007747.
VARIANT     373    373       H -> Y (in DDS).
                             /FTId=VAR_015056.
VARIANT     377    377       H -> R (in DDS).
                             /FTId=VAR_015057.
VARIANT     377    377       H -> Y (in NPHS4).
                             /FTId=VAR_007748.
VARIANT     379    379       G -> C (in NPHS4).
                             /FTId=VAR_043804.
VARIANT     383    383       F -> L (in NPHS4).
                             /FTId=VAR_007749.
VARIANT     385    385       C -> R (in DDS).
                             /FTId=VAR_015058.
VARIANT     388    388       C -> F (in DDS).
                             /FTId=VAR_015059.
VARIANT     388    388       C -> R (in NPHS4).
                             /FTId=VAR_043805.
VARIANT     388    388       C -> Y (in DDS).
                             /FTId=VAR_043806.
VARIANT     392    392       F -> L (in FS).
                             /FTId=VAR_015060.
VARIANT     394    394       R -> L (in WT1).
                             /FTId=VAR_043807.
VARIANT     394    394       R -> P (in DDS).
                             /FTId=VAR_043808.
VARIANT     394    394       R -> Q (in DDS).
                             /FTId=VAR_015061.
VARIANT     394    394       R -> W (in DDS, WT1 and MEACHS).
                             /FTId=VAR_007750.
VARIANT     396    396       D -> G (in DDS).
                             /FTId=VAR_007752.
VARIANT     396    396       D -> N (in DDS and NPHS4).
                             /FTId=VAR_007751.
VARIANT     396    396       D -> Y (in DDS).
                             /FTId=VAR_043809.
VARIANT     397    397       H -> P (in NPHS4).
                             /FTId=VAR_043810.
VARIANT     398    398       L -> P (in DDS).
                             /FTId=VAR_015062.
VARIANT     401    401       H -> Y (in DDS).
                             /FTId=VAR_043811.
VARIANT     405    405       H -> R (in DDS).
                             /FTId=VAR_043812.
MUTAGEN      73     73       K->R: Abolishes sumoylation; when
                             associated with R-177.
MUTAGEN     177    177       K->R: Abolishes sumoylation; when
                             associated with R-77.
MUTAGEN     343    343       H->A: Reduced RNA binding.
MUTAGEN     366    366       R->A: Strongly reduced binding of DNA and
                             RNA.
MUTAGEN     372    372       R->A: Strongly reduced binding of DNA and
                             RNA.
MUTAGEN     394    394       R->A,S: Strongly reduced binding of DNA
                             and RNA.
MUTAGEN     434    434       H->A: Reduced RNA binding.
CONFLICT    288    288       I -> M (in Ref. 8; AAH32861).
CONFLICT    365    365       S -> F (in Ref. 9; AAA36810 and 10;
                             AAB33443).
CONFLICT    387    387       T -> A (in Ref. 3; CAA43819).
STRAND      322    324
TURN        328    330
STRAND      333    337
HELIX       338    344
HELIX       345    349
STRAND      363    366
HELIX       367    378
TURN        386    388
STRAND      391    393
HELIX       395    406
STRAND      418    420
STRAND      424    427
HELIX       428    435
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Nucleotide Sequence
Length: 3020 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 449 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
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