RAP80: Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly Act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. Interacts with TSP57. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with FAM175A/Abraxas. Interacts with ESR1, NR6A1 and UBE2I. Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis. Belongs to the RAP80 family. 5 isoforms of the human protein are produced by alternative splicing.
Protein type: Nuclear receptor co-regulator; Transcription, coactivator/corepressor
Chromosomal Location of Human Ortholog: 5q35.2
Cellular Component: nucleus
Molecular Function: retinoid X receptor binding; protein binding; histone binding
Biological Process: positive regulation of DNA repair; transcription, DNA-dependent; double-strand break repair; response to ionizing radiation; G2/M transition DNA damage checkpoint; negative regulation of transcription, DNA-dependent
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