APC membrane recruitment protein 1 (AMER1) or Wilms Tumor on the X (WTX) gene, also known as FAM123B, comprises adenomatous polyposis coli (APC) interacting domains, nuclear localization signal (NLS), phospholipid binding region, six conserved block sequences and β-catenin binding region. The N-terminal region harbors the internal splicing sites (donor and acceptor). It encodes three isoforms AMER1, AMER2 and AMER3 APC, by alternative splicing at the N-terminus. WTX gene is localized on the X chromosome. The phosphatidylinositol (4,5)-bisphosphate binding site of the WTX aids its localization to the plasma membrane.
Specificity
Anti-WTX (N-terminal) specifically recognizes human WTX.
Application
Anti-WTX (N-terminal) antibody produced in rabbit has been used in chromatin immunoprecipitation[1] and immunoblotting.
Biochem/physiol Actions
APC membrane recruitment protein 1 (AMER1) or WTX is localized in the subnuclear compartment and participates in RNA processing, transcription and cell differentiation. In cultured cells, WTX negatively regulates the WNT/β-catenin signaling by promoting β-catenin ubiquitination and thus targets its degradation by the proteasome. WTX has been shown to form a complex with β-catenin, Axis inhibition protein 1 (AXIN1), β-transducin repeat containing protein 2 (β-TrCP2) and adenomatous polyposis coli (APC). WTX mutations are majorly somatic and the gene deletions and truncations is implicated in 30% of Wilms tumors. The mutations were confined to the active X and single X chromosomes in females and males respectively.. Loss of WTX function in Wilms tumor results in stabilization of β-catenin and its translocation to the nucleus. WTX co-localizes with non-POU domain-containing octamer-binding protein (p54nrb/NONO) and binds Wilms′ tumor protein 1 (WT1) to modulate its activity, suggesting that WTX may play a role in the transcriptional regulation.
Physical form
Solution in 0.01 M phosphate buffered saline, pH 7.4, containing 15 mM sodium azide.
Storage and Stability
For continuous use, store at 2–8 °C for up to one month. For extended storage, freeze in working aliquots. Repeated freezing and thawing, or storage in “frost-free” freezers, is not recommended. If slight turbidity occurs upon prolonged storage, clarify the solution by centrifugation before use. Working dilutions should be discarded if not used within 12 hours.
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WTX is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical Wnt/β-catenin signaling in fish and
Abnormalities in WNT signaling are implicated in a broad range of developmental anomalies and also in tumorigenesis. Here we demonstrate that germline mutations in WTX (FAM123B), a gene that encodes a repressor of canonical WNT signaling, cause an X-linked sclerosing
Proceedings of the National Academy of Sciences of the United States of America, 106(20), 8338-8343 (2009-05-07)
WTX encodes a tumor suppressor gene inactivated in Wilms tumor and recently implicated in WNT signaling through enhancement of cytoplasmic beta-catenin (CTNNB1) degradation. Here, we report that WTX translocates to the nucleus, a property that is modified by an endogenous
Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break
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