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FLASH GENE
Symbol BAP1 contributors: mct/npt/pgu - updated : 29-11-2016
HGNC name BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)
HGNC id 950
Location 3p21.2      Physical location : 52.435.026 - 52.444.009
Synonym name
  • ubiquitin carboxyl-terminal hydrolase BAP1
  • cerebral protein 6
  • cerebral protein-13
  • Synonym symbol(s) KIAA0272, hucep-6, DKFZp686N04275, FLJ35406, FLJ37180, HUCEP-13
    EC.number 3.4.19.12
    DNA
    TYPE functioning gene
    STRUCTURE 8.98 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    SRISNF2L 3p21.31 KIAA0809 protein ZSIG11 3p21.31 putative secreted protein ZSIG11 GRM2 3p21.3-p21.2 glutamate receptor, metabotropic 2 LOC389121 3 LOC389121 LOC389122 3 hypothetical gene supported by BC021188 LOC389123 3 similar to hypothetical protein MGC39725 LOC389124 3 similar to hypothetical protein MGC39725 MGC39725 3p21.31 hypothetical protein MGC39725 RNU3IP2 3p21.31 RNA, U3 small nucleolar interacting protein 2 ADPRTL3 3p22.2-p21.1 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)-like 3 GPR62 3p21.1 G protein-coupled receptor 62 PCBP4 3p21 poly(rC) binding protein 4 MGC15429 3p21.31 hypothetical protein MGC15429 DKFZP564O243 3p21.1 DKFZP564O243 protein ACY1 3p21.1 aminoacylase 1 RPL29 3q29 ribosomal protein L29 DUSP7 3p21.1 dual specificity phosphatase 7 DKFZP434C245 3p21.31 DKFZP434C245 protein LOC391538 3 similar to fructose-1,6-bisphosphate aldolase A ALAS1 3p21.1 aminolevulinate, delta-, synthase 1 TLR9 3p21.3 toll-like receptor 9 PTK9L 3p21.1 PTK9L protein tyrosine kinase 9-like (A6-related protein) FLJ32332 3p21.31 likely ortholog of mouse protein phosphatase 2C eta PRO2730 3p21.31 hypothetical protein PRO2730 GLYCTK 3p21.31 CG9886-like PPP2R5CP 3p21.3 protein phosphatase 2, regulatory subunit B (B56), gamma isoform pseudogene BAP1 3p21.31-p21.2 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) PHF7 3p21.31 PHD finger protein 7 LOC56920 3p21.31 semaphorin sem2 TNNC1 3p21.3-p14.3 troponin C, slow NISCH 3p21.1 nischarin STAB1 3p21.31 stabilin 1 FLJ12442 3p21.31 hypothetical protein FLJ12442 PB1 3p21 hypothetical protein FLJ12442 NS 3p21.31 nucleostemin AD-017 3p21.31 glycosyltransferase AD-017 SPC12 3p21.31 signal peptidase 12kDa NEK4 3p21.1 NIMA (never in mitosis gene a)-related kinase 4 ITIH1 3p21.2-p21.1 inter-alpha (globulin) inhibitor, H1 polypeptide ITIH3 3p21.2-p21.1 pre-alpha (globulin) inhibitor, H3 polypeptide ITIH4 3p21.2-p21.1 inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein) LOC389125 3 similar to hypothetical protein MGC52022 3p21.31 Similar to RIKEN cDNA 1810038N08 gene SFMBT1 3p21.31 Scm-like with four mbt domains 1 LOC285398 3p21.31 hypothetical protein LOC285398 RFT1 3p21.31 putative endoplasmic reticulum multispan transmembrane protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 3599 - 729 in all tissues 1998 9528852
    - - - 4800 - - specificaly in testis 1998 9528852
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Nervousnerve   highly
    Reproductivemale systemprostate  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an acidic region
  • two putative nuclear localizatin signals, one of the two predicted nuclear targeting motifs is required for nuclear localization of BAP1
  • a coiled-coil motif, for directly interacting with the zinc fingers of YY1
  • HCFC1 binding motif required for interaction with HCF-1N and mediates deubiquitination of HCF-1N by BAP1
  • binding domains for BRCA1 and BARD1
  • highly charged C-terminal region, and extended C terminus, which may be involved in interaction with other proteins
  • ubiquitin C-terminal hydrolase (UCH) domain
  • HOMOLOGY
    interspecies homolog to murine Bap1
    ortholog to drosophila Calypso
    Homologene
    FAMILY
  • peptidase C12 family, UCH family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • associate with chromatin
  • basic FUNCTION
  • ubiquitin carboxy-terminal hydrolase
  • binding to the BRCA1 RING finger domain and enhancing BRCA1-mediated cell growth suppression
  • deubiquitinating enzyme having tumor suppressor activity
  • helps to control cell proliferation by regulating HCFC1 protein levels and by associating with genes involved in the G(1)-S transition)
  • plays important roles in cell growth and tumor suppression
  • functionally implicated in numerous biologic processes, including chromatin dynamics, DNA damage response, and regulation of the cell cycle and cell growth
  • a deubiquitinating enzyme (DUB) involved in the regulation of cell proliferation
  • activates transcription in an enzymatic-activity-dependent manner and regulates the expression of a variety of genes involved in numerous cellular processes
  • transcriptional coactivator that regulates the expression of genes involved in numerous cellular processes
  • might play an important role in dynamically controlling transcriptional responses that coordinate mitochondrial function
  • role for BAP1 in the regulation of Polycomb target gene expression in malignant pleural mesothelioma cells
  • has an important tumor suppressor function in multiple tissues
  • repressed cell proliferation without causing apoptosis
  • potent tumor suppressor function for BAP1 in myeloid neoplasia
  • renal cell carcinomas-predisposition gene
  • is a deubiquitinase required for efficient assembly of the homologous recombination (HR) factors BRCA1 and RAD51 at ionizing radiation (IR) -induced foci
  • important role for BAP1 in DSB repair by HR, thereby providing a possible molecular basis for its tumor suppressor function
  • functions as part of the DNA damage response (DDR)
  • promoted repair of DNA double-strand breaks, enhancing cell survival after DNA damage
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text negative control of cell proliferation
    PATHWAY
    metabolism
    signaling
    a component
  • components of the ubiquitin proteasome system
  • assembled BAP1/HCFC1/YY1 complex acts to induce the activation of COX7C or other target genes
  • BAP1 forms a core complex with HCFC1 and OGT that can differentially recruit additional histone-modifying enzymes to regulate gene expression and thereby preserve normal hematopoiesis
  • UCHL3 and UCHL5 are considered to be tumor promoters, while BAP1 is considered to be a tumor suppressor, and UCH enzymes influence several signaling pathways that play crucial roles in oncogenesis, tumor invasion, and migration
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HCFC1 is a critical target of BAP1 in growth regulation (interaction plays a pivotal role in regulation of cell growth by BAP1)
  • BRCA1-associated protein
  • interacting with YY1, and HCFC1 is required for this interaction
  • nuclear deubiquitinase known to target histones (together with ASXL1 as a Polycomb repressor subunit) and the HCF1 transcriptional co-factor
  • binding of BAP1 to HCFC1 is likely to be important for BAP1-mediated suppression of RCC (renal cell carcinoma) development
  • UBE2O multi-monoubiquitinates the nuclear localization signal of BAP1, thereby inducing its cytoplasmic sequestration
  • is a phosphorylation target for the DDR kinase ATM
  • BAP1 could bind to E2F1 responsive promoters and the localization of BAP1 to E2F1-responsive promoters is host cell factor-1 dependent
  • ASXL1 and ASXL2 use their ASXM domains to interact with the C-terminal domain (CTD) of BAP1, and these interactions are required for ubiquitin binding and HIST2H2AC deubiquitination
  • BAP1 interaction with ASXL2 regulates cell senescence and ASXL2 cancer-associated mutations disrupt BAP1 DUB activity
  • BAP1 C-terminal extension is important for HIST2H2AC deubiquitination by auto-recruiting BAP1 to nucleosomes in a process that does not require the nucleosome acidic patch
  • BAP1 is activated by ASXL1 to deubiquitinate mono-ubiquitinated HIST2H2AC
  • cell & other
    REGULATION
    Other regulated by deubiquitination of HCFC1 (deubiquitination of HCFC1 is a crucial step in BAP1-mediated growth regulation)
    is phosphorylated at serine 592 in S-phase following DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in breast cancer
    tumoral   deletion    
    in lung carcinoma
    tumoral   deletion    
    in uveal melanoma metastasis
    tumoral somatic mutation     loss of function
    in malignant pleural mesothelioma
    tumoral germinal mutation      
    in two putatively distinct cancer-related syndromes characterized predominantly by melanocytic tumors or mesothelioma, respectively, along with uveal melanoma
    tumoral germinal mutation      
    in melanocytic tumors
    tumoral germinal mutation      
    predispose to malignant mesothelioma
    tumoral germinal mutation      
    in familial nonsyndromic renal cell carcinomas (RCC)
    tumoral       loss of function
    in clear cell RCCs
    tumoral       loss of function
    restricted to the hematopoietic compartment is sufficient for the development of myeloid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    important target for anticancer drugs
    cancereye 
    BAP1 pathway may be a valuable therapeutic targetin uveal melanoma
    ANIMAL & CELL MODELS
  • mouse Bap1 gene deletion is lethal during embryogenesis, but systemic or hematopoietic-restricted deletion in adults recapitulates features of human myelodysplastic syndrome (MDS)