Protein: Ubiquitin carboxyl-terminal hydrolase BAP1 (EC 3.4.19.12) (BRCA1-associated protein 1) (Cerebral protein 6) (Q92560)
Organism: Homo sapiens (Human)
Function: Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B. Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains. Deubiquitination of HCFC1 does not lead to increase stability of HCFC1. Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination. It however does not mediate deubiquitination of BRCA1 and BARD1. Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration. Acts as a tumor suppressor.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:24703950}. Nucleus {ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:24748658, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:35051358, ECO:0000269|PubMed:35446349, ECO:0000269|PubMed:9528852}. Chromosome {ECO:0000269|PubMed:30664650}. Note=Mainly nuclear (PubMed:24703950, PubMed:30664650). Binds to chromatin (PubMed:30664650). Localizes to the cytoplasm when monoubiquitinated by the E2/E3 hybrid ubiquitin-protein ligase UBE2O (PubMed:24703950). Recruitment to chromatin is dependent on ASXL1/2/3 and recruitment to specific genes on FOXK1/2 (By similarity). Nuclear localization is redundantly mediated by the importin and transportin systems; TNPO1/transportin-1 is the major mediator of nuclear localization (PubMed:35446349). {ECO:0000250|UniProtKB:Q99PU7, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:35446349}.
Interaction partners:
- Putative Polycomb group protein ASXL2
- Polycomb group protein ASXL1
- Host cell factor 1
- Breast cancer type 1 susceptibility protein
- BRCA1-associated RING domain protein 1
- Forkhead box protein K1
- UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit
- Histone-binding protein RBBP7
- AOF1 protein
- Forkhead box protein K2
Sequence:
MNKGWLELESDPGLFTLLVEDFGVKGVQVEEIYDLQSKCQGPVYGFIFLFKWIEERRSRRKVSTLVDDTSVIDDDIVNNMFFAHQLIPNSCATHALLSVLLNCSSVDLGPTLSRMKDFTKGFSPESKGYAIGNAPELAKAHNSHARPEPRHLPEKQNGLSAVRTMEAFHFVSYVPITGRLFELDGLKVYPIDHGPWGEDEEWTDKARRVIMERIGLATAGEPYHDIRFNLMAVVPDRRIKYEARLHVLKVNRQTVLEALQQLIRVTQPELIQTHKSQESQLPEESKSASNKSPLVLEANRAPAASEGNHTDGAEEAAGSCAQAPSHSPPNKPKLVVKPPGSSLNGVHPNPTPIVQRLPAFLDNHNYAKSPMQEEEDLAAGVGRSRVPVRPPQQYSDDEDDYEDDEEDDVQNTNSALRYKGKGTGKPGALSGSADGQLSVLQPNTINVLAEKLKESQKDLSIPLSIKTSSGAGSPAVAVPTHSQPSPTPSNESTDTASEIGSAFNSPLRSPIRSANPTRPSSPVTSHISKVLFGEDDSLLRVDCIRYNRAVRDLGPVISTGLLHLAEDGVLSPLALTEGGKGSSPSIRPIQGSQGSSSPVEKEVVEATDSREKTGMVRPGEPLSGEKYSPKELLALLKCVEAEIANYEACLKEEVEKRKKFKIDDQRRTHNYDEFICTFISMLAQEGMLANLVEQNISVRRRQGVSIGRLHKQRKPDRRKRSRPYKAKRQ