الفهرس 
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Abstract
Loss or inactivation of BAP1 may occur as a result of chromosomal deletions involving the BAP1 gene locus, or due to sequence variation in the BAP1 gene. Several different alterations in the BAP1 gene have been reported, including large deletions of exons leading to loss of the N-terminal region or to premature protein termination. Carriers of germline BAP1 mutations often develop multiple cancers during their lifetime. The overall penetrance for cancer is at least 85% and approaches 100% with increasing age. The 729-amino acid BAP1 protein includes a carboxy-terminal hydrolase domain located at its N-terminal region, and binding domains for BRCA1 (Breast Cancer 1), BARD1 (BRCA1-associated RING domain protein 1), and HCF1 (Host cell factor 1), among others. Finally, at its C-terminal region, BAP1 contains two nuclear localization signals (NLS1, NLS2) that determine where its primary functions occur. BAP1 protein is found in both the nucleus and the cytoplasm. As BAP1 has nuclear localization signals at its C-terminal region; thus, truncating mutations impair BAP1 nuclear translocation. The ubiquitin conjugating enzyme UBE2O induces BAP1 sequestration in the cytoplasm by multi-monoubiquitination of its nuclear localization signal (NLS). BAP1 counteracts this mechanism and regulates its own nuclear