BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) is a deubiquitinating enzyme that in humans is encoded by the BAP1 gene.[5][6] BAP1 encodes an 80.4 kDa nuclear-localizing protein with a ubiquitin carboxy-terminal hydrolase (UCH) domain that gives BAP1 its deubiquitinase activity.[5] Recent studies have shown that BAP1 and its fruit fly homolog, Calypso, are members of the polycomb-group proteins (PcG) of highly conserved transcriptional repressors required for long-term silencing of genes that regulate cell fate determination, stem cell pluripotency, and other developmental processes.[7]
BAP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | BAP1, HUCEP-13, UCHL2, hucep-6, BRCA1 associated protein 1, KURIS | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 603089 MGI: 1206586 HomoloGene: 3421 GeneCards: BAP1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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BAP1 is also known as:
In humans, BAP1 is encoded by the BAP1 gene located on the short arm of chromosome 3 (3p21.31-p21.2).
Human BAP1 is 729 amino acids long and has three domains:
In both Drosophila and humans, BAP1 functions as the catalytic subunit of the Polycomb repressive deubiquitinase (PR-DUB) complex, which controls homeobox genes by regulating the amount of ubiquitinated Histone H2A in Nucleosomes bound to their promoters. In flies and humans, the PR-DUB complex is formed through the interaction of BAP1 and ASXL1 (Asx in fruit flies)[8][9] BAP1 has also been shown to associate with other factors involved in chromatin modulation and transcriptional regulation, such as Host cell factor C1,[10][11][12] which acts as an adaptor to couple E2F transcription factors to chromatin-modifying complexes during cell cycle progression.
In cancer, BAP1 can function both as a tumor suppressor and as a metastasis suppressor.
Two studies used genome sequencing independently to identify germline mutations in BAP1 in families with genetic predispositions to mesothelioma[17] and melanocytic skin tumors[18] The atypical melanocytic lesions resemble Spitz nevi and have been characterized as "atypical Spitz tumors" (ASTs), although they have a unique histology and exhibit both BRAF and BAP1 mutations.[19] Further studies have identified germline BAP1 mutations associated with other cancers.[20] These studies suggest that germline mutation of BAP1 results in a Tumor Predisposition Syndrome linking BAP1 to many more cancers.
Immunohistochemistry for BAP1 is a prognostic biomarker to predict poor oncologic outcomes and adverse clinicopathological features in patients with non-metastatic clear cell renal cell carcinoma (CCRCC). BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning.[21]
BAP1 has been shown to interact with