BAP1

BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) is a deubiquitinating enzyme that in humans is encoded by the "BAP1" gene. "BAP1" encodes an 80.4 kDa nuclear-localizing protein with a ubiquitin carboxy-terminal hydrolase (UCH) domain that gives BAP1 its deubiquitinase activity. 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.
Nomenclature.
BAP1 is also known as:
Gene.
In humans, BAP1 is encoded by the "BAP1" gene located on the short arm of chromosome 3 (3p21.31-p21.2).
Structure.
Human BAP1 is 729 amino acids long and has three domains:
Function.
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) BAP1 has also been shown to associate with other factors involved in chromatin modulation and transcriptional regulation, such as Host cell factor C1, which acts as an adaptor to couple E2F transcription factors to chromatin-modifying complexes during cell cycle progression.
Role in disease.
In cancer, BAP1 can function both as a tumor suppressor and as a metastasis suppressor.
BAP1 tumor predisposition syndrome.
Two studies used genome sequencing independently to identify germline mutations in BAP1 in families with genetic predispositions to mesothelioma and melanocytic skin tumors 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. 
Further studies have identified germline BAP1 mutations associated with other cancers. These studies suggest that germline mutation of BAP1 results in a Tumor Predisposition Syndrome linking BAP1 to many more cancers.
Immunochemistry.
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.
Interactions.
BAP1 has been shown to interact with
Model organisms.
Model organisms have been used in the study of BAP1 function. A conditional knockout mouse line called "Bap1tm1a(EUCOMM)Hmgu" was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping - in-depth bone and cartilage phenotyping 