WT1
Encyclopedia
Wilms tumor protein is a protein
that in humans is encoded by the WT1 gene
.
that contains four zinc finger
motifs at the C-terminus and a proline
/ glutamine
-rich DNA-binding domain
at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms' tumor
, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.
The WT1 protein has been found to bind a host of cellular factors, e.g. p53
, a known tumor suppressor.
binds to WT1 and it cleaves WT1 at multiple sites following the treatment with cytotoxic drugs.
with U2AF2
, PAWR
, UBE2I
and WTAP
.
of human WT1 mRNA.As with alternative splicing
of the gene RNA editing increases the number of isoforms of this protein.
to Cytidine
( U to C) base change .The editing reaction is thought to be an amidation of uridine which converts it to a Cytidine.The relevance of this editing is unknown as is the enzyme responsible for this editing.The region where editing occurs like that of other editing sites e.g ApoB mRNA editing is conserved.Mice , rat and humans have conserved sequences flanking the editing site consiting of 10 nucleotides before the editing site and four after the site.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the WT1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes a transcription factorTranscription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
that contains four zinc finger
Zinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
motifs at the C-terminus and a proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
/ glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
-rich DNA-binding domain
DNA-binding domain
A DNA-binding domain is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA...
at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a subset of patients with Wilms' tumor
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.
The WT1 protein has been found to bind a host of cellular factors, e.g. p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, a known tumor suppressor.
Degradation
The serine protease HtrA2HtrA serine peptidase 2
Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene.-Interactions:HtrA serine peptidase 2 has been shown to interact with MAPK14, XIAP and BIRC2.-External Links:...
binds to WT1 and it cleaves WT1 at multiple sites following the treatment with cytotoxic drugs.
Interactions
WT1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with U2AF2
U2AF2
Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.-Interactions:U2AF2 has been shown to interact with WT1, PUF60, SFRS2IP, SRPK2, SF1, U2 small nuclear RNA auxiliary factor 1 and SFRS11.-References:...
, PAWR
PAWR
PRKC, apoptosis, WT1, regulator, also known as PAWR or Prostate apoptosis response-4 , is a human gene coding for a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells....
, UBE2I
UBE2I
SUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
and WTAP
WTAP (gene)
Pre-mRNA-splicing regulator WTAP is a protein that in humans is encoded by the WTAP gene.-Interactions:WTAP has been shown to interact with WT1.-Further reading:...
.
Rna Editing
There is some evidence for RNA editingRNA editing
The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA, rRNA, mRNA and microRNA molecules of eukaryotes but not prokaryotes...
of human WT1 mRNA.As with alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
of the gene RNA editing increases the number of isoforms of this protein.
Editing Type
The type of editing is a UridineUridine
Uridine is a molecule that is formed when uracil is attached to a ribose ring via a β-N1-glycosidic bond.If uracil is attached to a deoxyribose ring, it is known as a deoxyuridine....
to Cytidine
Cytidine
Cytidine is a nucleoside molecule that is formed when cytosine is attached to a ribose ring via a β-N1-glycosidic bond...
( U to C) base change .The editing reaction is thought to be an amidation of uridine which converts it to a Cytidine.The relevance of this editing is unknown as is the enzyme responsible for this editing.The region where editing occurs like that of other editing sites e.g ApoB mRNA editing is conserved.Mice , rat and humans have conserved sequences flanking the editing site consiting of 10 nucleotides before the editing site and four after the site.