BRCC36 is a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. (1). It is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains, and does not have activity toward 'Lys-48'-linked polyubiquitin chains. In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs). BRCC36 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. It is aberrantly expressed in the vast majority of breast tumors (2). This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint (1).
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