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histone-fold domain found in centromere protein X (CENP-X) and similar proteins CENP-X, also called MHF2, FANCM-associated histone fold protein 2, FANCM-interacting histone fold protein 2, Fanconi anemia-associated polypeptide of 10 kDa, retinoic acid-inducible gene D9 protein homolog, or stimulated by retinoic acid gene 13 protein homolog, is a DNA-binding component of the Fanconi anemia (FA) core complex. It is required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage. CENP-X, together with CENP-S, forms the MHF heterodimer, which can further assemble to form tetrameric structures. CENP-X acts as a crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. It can stabilize FANCM. CENP-X also forms a discrete complex with FANCM and CENP-S, called FANCM-MHF. This interaction leads to synergistic activation of double-stranded DNA binding and strongly stimulates FANCM-mediated DNA remodeling. In complex with CENP-T, CENP-W and CENP-S (CENP-T-W-S-X heterotetramer), CENP-X is involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression. As a component of the MHF and CENP-T-W-S-X complexes, CENP-X binds DNA and bends it to form a nucleosome-like structure. Its DNA-binding function is fulfilled in the presence of CENP-S. It does not bind DNA on its own. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",