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Beschreibung

Polycomb group protein ASXL1 (UniProt: Q8IXJ9, also known as Additional sex combs-like protein 1) is encoded by the ASXL1 (also known as KIAA0978) gene (Gene ID: 171023) in human. ASXL1 is a member of the ASXL family that is expressed at low levels in various tissues. However, higher expression is reported in testes. It is a member of the ASXL family with a highly conserved ASX homology (ASXH) domain at the N-terminal region and a plant homeodomain (PHD) finger (aa 1503-1540) at the C-terminal region. The ASXH domain mediates its interaction with a partner protein BAP1, which is an essential component of the polycomb repressive deubiquinase complex (PR-DUB), in which it is involved in deubiquitination of monoubiquitinated histone H2A at lysine 119 (H2AK119ub). ASXL1 also acts as a sensor of N6-methyladenosine methylation on DNA (m6A). It recognizes and binds m6A DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating polycomb silencing. Its HARE-HTH-type domain (aa 11-86) recognizes and binds m6A. Mutations in ASXL1 gene are known to perturb development and cause Bohring-Opitz syndrome that is characterized by severe intrauterine growth retardation, poor feeding, and mental retardation. Some mutations are also observed in myeloid neoplasms, including myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia and are associated with poor prognosis. (Ref.: Matheus, F., et al. (2019). Stem Cell Reports 12(5), 861-868, Asada, S., et al. (2018). Nat. Commun. 9: Article 2733, Scheuermann, JC., et al. (2010). Nature. 465(7295), 243-247).