BAP1

This gene belongs to the ubiquitin C-terminal hydrolase subfamily of deubiquitinating enzymes that are involved in the removal of ubiquitin from proteins. The encoded enzyme binds to the breast cancer type 1 susceptibility protein (BRCA1) via the RING finger domain of the latter and acts as a tumor suppressor. In addition, the enzyme may be involved in regulation of transcription, regulation of cell cycle and growth, response to DNA damage and chromatin dynamics. Germline mutations in this gene may be associated with tumor predisposition syndrome (TPDS), which involves increased risk of cancers including malignant mesothelioma, uveal melanoma and cutaneous melanoma. [provided by RefSeq, May 2013]

BRCA1 Associated Protein 1

Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1 (PubMed:12485996, PubMed:18757409, PubMed:20436459, PubMed:25451922).
Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459, PubMed:25451922).
Does not deubiquitinate monoubiquitinated histone H2B (PubMed:20436459).
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 (PubMed:19188440, PubMed:19815555).
Deubiquitination of HCFC1 does not lead to increase stability of HCFC1 (PubMed:19188440, PubMed:19815555).
Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination (PubMed:19117993).
It however does not mediate deubiquitination of BRCA1 and BARD1 (PubMed:19117993).
Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950).
Acts as a tumor suppressor (PubMed:9528852).

Cellular protein modification process Source: UniProtKB
Double-strand break repair Source: Reactome
Macrophage homeostasis Source: Ensembl
Monoubiquitinated histone H2A deubiquitination Source: UniProtKB
Monoubiquitinated protein deubiquitination Source: UniProtKB
Negative regulation of cell population proliferation Source: ProtInc
Negative regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
Protein deubiquitination Source: UniProtKB
Protein K48-linked deubiquitination Source: UniProtKB
Regulation of cell cycle Source: UniProtKB
Regulation of cell growth Source: UniProtKB
Regulation of cytokine production involved in inflammatory response Source: Ensembl
Regulation of inflammatory response Source: Ensembl
Response to inorganic substance Source: Ensembl
Ubiquitin-dependent protein catabolic process Source: InterPro

Nucleus; Cytoplasm. Mainly nuclear. Binds to chromatin. Localizes to the cytoplasm when monoubiquitinated by the E2/E3 hybrid ubiquitin-protein ligase UBE2O (PubMed:24703950).

Mesothelioma, malignant (MESOM): An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.
Tumor predisposition syndrome (TPDS): A condition characterized by predisposition to develop a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, lung adenocarcinoma and meningioma.

Ubiquitinated: monoubiquitinated at multiple site of its nuclear localization signal (NLS) BY UBE2O, leading to cytoplasmic retention. Able to mediate autodeubiquitination via intramolecular interactions to couteract cytoplasmic retention.