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FLASH GENE
Symbol BBC3 contributors: mct/shn - updated : 02-05-2018
HGNC name BCL2 binding component 3
HGNC id 17868
Location 19q13.32      Physical location : 47.724.079 - 47.736.023
Synonym name
  • PUMA/JFY1 protein
  • p53 up-regulated modulator of apoptosis
  • JFY-1
  • bcl-2-binding component 3
  • Synonym symbol(s) JFY1, PUMA, FLJ42994
    DNA
    TYPE functioning gene
    STRUCTURE 11.95 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • TP53 responsive element in the promoter
  • EZH2 directly binds to the BBC3 promoter thus epigenetic repression of BBC3 expression
  • MAPPING cloned Y linked N status provisional
    Map cen - D19S219 - D19S412 - BBC3 - D19S606 - D19S902 - qter
    Physical map
    LOC390946 19 similar to Serine/threonine protein phosphatase 5 (PP5) (Protein phosphatase T) (PP-T) (PPT) LOC390947 19 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) CALM3 19q13.3 calmodulin 3 (phosphorylase kinase, delta) PTGIR 19q13.3 prostaglandin I2 (prostacyclin) receptor (IP) GNG8 19q13.2-q13.3 guanine nucleotide binding protein (G protein), gamma 8 MGC15476 19q13.33 thymus expressed gene 3-like PRKD2 19q13.2 thymus expressed gene 3-like STRN4 19q13.2 striatin, calmodulin binding protein 4 FKRP 19q13.33 fukutin related protein SLC1A5 19q13.3 solute carrier family 1 (neutral amino acid transporter), member 5 LOC390948 19 similar to heterogeneous nuclear ribonucleoprotein M isoform a; heterogenous nuclear ribonucleoprotein M4; N-acetylglucosamine receptor 1; M4 protein; heterogenous nuclear ribonucleoprotein M AP2S1 19q13.2-q13.3 adaptor-related protein complex 2, sigma 1 subunit GRLF1 19q13.3 glucocorticoid receptor DNA binding factor 1 NPAS1 19q13.2-q13.3 neuronal PAS domain protein 1 FLJ20512 19q13.33 hypothetical protein FLJ20512 C19orf7 19q13.33 chromosome 19 open reading frame 7 SAE1 19q13.33 SUMO-1 activating enzyme subunit 1 BBC3 19q13.3-q13.4 BCL2 binding component 3 DKFZP586M1019 LOC255783 19q13.33 hypothetical protein LOC255783 C5R1 19q13.3-q13.4 complement component 5 receptor 1 (C5a ligand) GPR77 19q13.33 G protein-coupled receptor 77 DHX34 19q13.3 DEAH (Asp-Glu-Ala-His) box polypeptide 34 MRG2 KPTN 19q13.3 kaptin (actin binding protein) NAPA 19q13.3 N-ethylmaleimide-sensitive factor attachment protein, alpha DKFZp434I1930 GLTSCR1 19q13.3 glioma tumor suppressor candidate region gene 1 EHD2 19p13.3 EH-domain containing 2 GLTSCR2 19q13.3 glioma tumor suppressor candidate region gene 2 SEPW1 19q13.3 selenoprotein W, 1 LOC390949 19 similar to 60S ribosomal protein L23a FLJ40321 19q13.33 FLJ40321 protein CRX 19q13.3 cone-rod homeobox SULT2A1 19q13.3 sulfotransferase family, cytosolic, 2A, dehydroepiandrosterone (DHEA) -preferring, member 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 1827 26.4 261 - 2009 19652530
  • isoform 1,
  • PUMA-gamma
  • 3 splicing 1538 14.3 131 - 2009 19652530
  • isoform 2
  • PUMA-beta
  • 2 splicing 1347 10.2 101 - 2009 19652530
  • isoform 3
  • PUMA-delta
  • 4 splicing 1843 20.4 193 - 2009 19652530
  • isoform 4
  • PUMA-alpha
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
    Nervousbrain    
    Reproductivemale systemprostate   
     male systemtestis   
    Urinarykidney    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • BH3 domain
  • HOMOLOGY
    interspecies ortholog to Bbc3, us musculus
    ortholog to bbc3, Danio rerio
    ortholog to Bbc3, Rattus norvegicus
    ortholog to BBC3, Pan troglodytes
    Homologene
    FAMILY
  • Bcl2 family of proteins responsible for maintaining mitochondrial outer membrane integrity by controlling the intrinsic (mitochondrial) apoptotic pathway
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic
    text
  • localized in the mitochondria and inducing apoptosis through the mitochondrial pathway
  • accumulation of BBC3 in the cytosol may be important for the participation of this protein in apoptosis without the need for prior transcription
  • basic FUNCTION
  • play a role in mediating TP53-induced cell death through the cytochrome c/Apaf-1-dependent pathway (
  • required for the apoptosis induced by overexpression of TP53, by hypoxia and DNA-damaging drugs
  • couples the nuclear and cytoplasmic proapoptotic functions of TP53
  • BH3-only Bcl-2 family protein and an essential mediator of DNA damage-induced apoptosis
  • regulation of expression may play a role in the development of hepatocellular carcinoma
  • plays a role in H2O2-induced apoptosis in colorectal cancer cells
  • imposes a significant barrier to c-Myc-driven lymphomagenesis
  • is competent to trigger Bax activity by itself
  • contributing to hepatocyte lipoapoptosis
  • critical roles in the depletion of adult stem cells induced by constitutively active TP53
  • essential for endoplasmic reticulum-stress-induced cell death (
  • estrogen target gene that mediates the apoptotic response to tamoxifen in human breast cancer cells
  • is essential for apoptosis of mitogen-activated B cells and for the control of memory B-cell survival
  • has a major role in the T cell- dependent B-cell immune response, and is a major regulator of memory B lymphocyte survival
  • is the more potent apoptosis inducer, because it can bind with high affinity to all pro-survival BCL2 family members
  • PMAIP1 and, albeit to a lesser extent, BBC3 are essential for DNA damage induced TP63-mediated killing of primordial follicle oocytes
  • PMAIP1 and BBC3 are critical for DNA damage-induced, TP63-mediated oocyte apoptosis
  • BCL2L11 and BBC3 can directly activate the proapoptotic proteins BAX and BAK1 to permeabilize mitochondria, leading to caspase activation and apoptosis
  • BCL2L11 and BBC3 are the sentinels that interconnect kinase signaling networks and the mitochondrion-dependent apoptotic program, which offers therapeutic insights for designing novel cell death mechanism-based anticancer strategies
  • is pivotal for oligodendroglial cell death induced by different cell death stimuli and might play a role in oligodendroglial cell death in multiple sclerosis (MS)
  • BBC3 mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in portal hypertensive gastropathy (PHG)
  • is a critical determinant of the number of germ cells during ovarian development
  • is a critical regulator of germ cell death that acts during the migratory phase of oogenesis or very soon after the arrival of germ cells in the gonad
  • is invovled in the apoptosis of cerebral astrocytes upon ischemia and reperfusion (I/R) injury
  • involvement of BBC3 in cold preservation/rewarming-mediated pancreatic islet injury, possibly through modulating HMGB1- and oxidative stress-mediated injury to islets
  • is a major regulator of apoptosis
  • involvement of PUMA in pericyte migration induced by methamphetamine 7)
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • BCL2 (
  • BCL2-associated X protein, BAX (
  • BCL2l1
  • TP53 transcription target required for TP53-dependent apoptosis after DNA damage
  • BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
  • PMAIP1 band BBC3 are target genes for TP53
  • BBC3 mediates the increased apoptosis and reduced proliferation within intestinal crypts that is induced by TLR4
  • cooperates with BCL2L11 to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease
  • TP63 but not TP53 is essential for DNA damage triggered transcriptional induction of BBC3 and PMAIP1 in primordial follicle oocytes
  • TP63 acts via transcriptional induction of the BH3-only proteins, BBC3 and PMAIP1 to cause apoptosis of DNA-damaged primordial follicle oocytes
  • SOX4 is required for BBC3-mediated apoptosis induced by histone deacetylase inhibitor, TSA
  • BBC3 like BCL2L11, PMAIP1, is able to act as a direct BAK1 activator
  • antagonism between MCL1 and BBC3 governs stem/progenitor cell survival during hematopoietic recovery from stress
  • BBC3 associates with HSPA8/HSC70 (heat shock 70kDa protein 8), leading to its lysosome translocation and uptake
  • MYSM1 is a critical negative regulator of TP53 transcriptional programs in hematopoiesis, and its repression of BBC3/PUMA expression is essential for multipotent progenitor (MPP) survival, and partly contributes to maintaining HSC function
  • EZH2-mediated BBC3 gene repression regulates non-small cell lung cancer cell proliferation and cisplatin-induced apoptosis
  • cell & other
    REGULATION
    activated by endoplasmic reticulum stress in cortical neurons at transcriptional level (
    induced by transcription facotrs Sp1 and p73 following serum starvation
    palmitate, in a JNK1-dependent manner
    p53 (
    repressed by scratch2 (
    Other regulated by p53 and Snail2 (
    HRK, BBC3, and PMAIP1 are transcriptionally induced in severe hypoxia and their expression is abrogated by RNA interference against ATF4
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast carcinomas is significantly associated with breast cancer-specific death
    constitutional       loss of function
    affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity
    constitutional       loss of function
    mediates the endogenous cardioprotective mechanisms of postconditioning by disrupting mitochondrial apoptotic pathway
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    feasible target to prevent depletion of adult stem cells in human patients with defective DNA repair pathways or patients undergoing radiation or chemotoxic cancer therapy
    cancer  
    PMAIP1-triggered BBC3-mediated apoptosis may be a powerful target for cancer therapy, especially early-stage cancer
    immunologyinflammatoryarticular
    therapeutic potential of BBC3 gene therapy as a local treatment in various forms of arthritis in which abnormal fibroblast-like synoviocytes (FLS) proliferation is implicated.
    digestiveliver 
    is a potentially therapeutic target for portal hypertensive gastropathy (PHG)
    ANIMAL & CELL MODELS
  • deletion of Bbc3 protects mice from the development of necrotizing enterocolitis and reversed the deleterious effects on crypt apoptosis and proliferation
  • mice lacking Puma have an increased supply of primordial follicle oocytes at baseline
  • mice with puma disrupted display decreased DNA damage-induced apoptosis in fibroblasts, lymphocytes are protected from cell death (
  • Puma triple-knockout mice showed the same developmental defects that are associated with deficiency of Bax and Bak, including persistent interdigital webs and imperforate vaginas (