InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BAP1

Summary

InnateDB Protein

IDBP-484468.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BAP1

Protein Name

BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)

Synonyms

HUCEP-13; UCHL2;

Species

Homo sapiens

Ensembl Protein

ENSP00000417132

InnateDB Gene

IDBG-38830 (BAP1)

Protein Structure

UniProt Annotation

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 (PubMed:24703950). Acts as a tumor suppressor. {ECO:0000269PubMed:12485996, ECO:0000269PubMed:18757409, ECO:0000269PubMed:19117993, ECO:0000269PubMed:19188440, ECO:0000269PubMed:19815555, ECO:0000269PubMed:20436459, ECO:0000269PubMed:24703950, ECO:0000269PubMed:9528852}.

Subcellular Localization

Cytoplasm. Nucleus. Note=Mainly nuclear. Binds to chromatin. Localizes to the cytoplasm when monoubiquitinated by the E2/E3 hybrid ubiquitin-protein ligase UBE2O (PubMed:24703950). {ECO:0000269PubMed:24703950}.

Disease Associations

Mesothelioma, malignant (MESOM) [MIM:156240]: 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. {ECO:0000269PubMed:21642991, ECO:0000269PubMed:21874000}. Note=The gene represented in this entry is involved in disease pathogenesis.Tumor predisposition syndrome (TPDS) [MIM:614327]: 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. {ECO:0000269PubMed:21874003}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Highly expressed in testis, placenta and ovary. Expressed in breast. {ECO:0000269PubMed:9528852}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 60 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	60 [view]
Protein-Protein	60 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0004221	ubiquitin thiolesterase activity
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008233	peptidase activity

Biological Process

GO:0001558	regulation of cell growth
GO:0006464	cellular protein modification process
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0008285	negative regulation of cell proliferation
GO:0016579	protein deubiquitination
GO:0035520	monoubiquitinated protein deubiquitination
GO:0035522	monoubiquitinated histone H2A deubiquitination
GO:0051726	regulation of cell cycle
GO:0071108	protein K48-linked deubiquitination