UIMC1
Description
The UIMC1 (ubiquitin interaction motif containing 1) is a protein-coding gene located on chromosome 5.
RAP80, the protein product of the UIMC1 gene, is a core component of the deubiquitin complex BRCA1-A. Other core components of the BRCA1-A complex are the BRCC36 protein (BRCC3 gene), BRE protein (BRE (gene)), and MERIT40 protein (BABAM1 gene). BRCA1, as distinct from BRCA1-A, is employed in the repair of chromosomal damage with an important role in the error-free homologous recombinational (HR) repair of DNA double-strand breaks. Sequestration of BRCA1 away from the DNA damage site suppresses homologous recombination and redirects the cell in the direction of repair by the process of non-homologous end joining (NHEJ).
UIMC1, also known as RAP80, is a ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. It plays a crucial role in the BRCA1-A complex by binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA damage sites. This binding targets the BRCA1-BARD1 heterodimer to these sites, promoting DNA repair at double-strand breaks (DSBs). The BRCA1-A complex also has deubiquitinase activity, specifically removing 'Lys-63'-linked ubiquitin from histones H2A and H2AX. While it can weakly bind monoubiquitin, its affinity for 'Lys-63'-linked ubiquitin is much stronger. UIMC1 may interact with monoubiquitinated histones H2A and H2B, but the significance of this interaction is unclear in vivo. It does not bind Lys-48'-linked ubiquitin. UIMC1 might indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1.
UIMC1 is also known as RAP80, X2HRIP110.
