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    BBC3 BCL2 binding component 3 [ Homo sapiens (human) ]

    Gene ID: 27113, updated on 14-Nov-2024

    Summary

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    Official Symbol
    BBC3provided by HGNC
    Official Full Name
    BCL2 binding component 3provided by HGNC
    Primary source
    HGNC:HGNC:17868
    See related
    Ensembl:ENSG00000105327 MIM:605854; AllianceGenome:HGNC:17868
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    JFY1; PUMA; JFY-1
    Summary
    This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
    Expression
    Ubiquitous expression in colon (RPKM 3.5), stomach (RPKM 1.4) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See BBC3 in Genome Data Viewer
    Location:
    19q13.32
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (47220824..47232860, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (50046144..50058334, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (47724081..47735924, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene zinc finger CCCH-type containing 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14853 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14854 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14855 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14856 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:47613025-47613752 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47615210-47615938 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47615939-47616666 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14858 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47633866-47634480 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47638584-47639354 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47639355-47640124 Neighboring gene SUMO1 activating enzyme subunit 1 Neighboring gene uncharacterized LOC124904730 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr19:47660297-47660840 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47660841-47661382 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47661383-47661925 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14860 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47692347-47693113 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47712248-47712997 Neighboring gene Sharpr-MPRA regulatory region 12080 Neighboring gene MPRA-validated peak3532 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:47728631-47729130 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:47729258-47729424 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10840 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47730339-47731281 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10842 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10843 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14861 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:47735673-47736296 Neighboring gene uncharacterized LOC124904731 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10844 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:47744377-47745178 Neighboring gene microRNA 3191 Neighboring gene microRNA 3190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14864 Neighboring gene CRISPRi-validated cis-regulatory element chr19.5064 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:47759131-47760040 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10848 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10849 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:47769923-47770422 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10850 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10851 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10852 Neighboring gene coiled-coil domain containing 9 Neighboring gene InaF motif containing 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. PUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells. Sun CG, et al. Genet Mol Res, 2015 May 29. PMID 26125773
    2. PUMA, a critical mediator of cell death--one decade on from its discovery. Hikisz P, et al. Cell Mol Biol Lett, 2012 Dec. PMID 23001513, Free PMC Article
    3. Prognostic significance of PUMA in pancreatic ductal adenocarcinoma. Du QH, et al. J Int Med Res, 2012. PMID 23321162
    4. PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Follis AV, et al. Nat Chem Biol, 2013 Mar. PMID 23340338, Free PMC Article
    5. The BH3-only protein Puma plays an essential role in p53-mediated apoptosis of chronic lymphocytic leukemia cells. Zhu HJ, et al. Leuk Lymphoma, 2013 Dec. PMID 23517560

    See all (238) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer.
      Title: Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer.
    2. PUMA overexpression dissociates thioredoxin from ASK1 to activate the JNK/BCL-2/BCL-XL pathway augmenting apoptosis in ovarian cancer.
      Title: PUMA overexpression dissociates thioredoxin from ASK1 to activate the JNK/BCL-2/BCL-XL pathway augmenting apoptosis in ovarian cancer.
    3. Recombinant human bone morphogenetic protein 2 and 7 inhibit the degeneration of intervertebral discs by blocking the Puma-dependent apoptotic signaling.
      Title: Recombinant human bone morphogenetic protein 2 and 7 inhibit the degeneration of intervertebral discs by blocking the Puma-dependent apoptotic signaling.
    4. PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells.
      Title: PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells.
    5. Long non-coding RNA HOTAIRincreased mechanical stimulation-induced apoptosis by regulating microRNA-221/BBC3 axis in C28/I2 cells.
      Title: Long non-coding RNA HOTAIRincreased mechanical stimulation-induced apoptosis by regulating microRNA-221/BBC3 axis in C28/I2 cells.
    6. Expression of p53 up-regulated modulator of apoptosis (PUMA) in non-melanoma skin cancer of long-term immunosuppressed solid organ transplant recipients compared to immunocompetent patients.
      Title: Expression of p53 up-regulated modulator of apoptosis (PUMA) in non-melanoma skin cancer of long-term immunosuppressed solid organ transplant recipients compared to immunocompetent patients.
    7. FBXL20 promotes breast cancer malignancy by inhibiting apoptosis through degradation of PUMA and BAX.
      Title: FBXL20 promotes breast cancer malignancy by inhibiting apoptosis through degradation of PUMA and BAX.
    8. The long non-coding RNA TSLC8 inhibits colorectal cancer by stabilizing puma.
      Title: The long non-coding RNA TSLC8 inhibits colorectal cancer by stabilizing puma.
    9. Genome-wide mRNA profiling identifies X-box-binding protein 1 (XBP1) as an IRE1 and PUMA repressor.
      Title: Genome-wide mRNA profiling identifies X-box-binding protein 1 (XBP1) as an IRE1 and PUMA repressor.
    10. Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
      Title: Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA.
    Submit: New GeneRIF Correction See all GeneRIFs (191)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Upregulation of Puma is required for HIV-1 gp120-mediated syncytial apoptosis PubMed
    env In cultured neurons, HIV-1 gp120 increases transcription factor E2F1 levels in the nucleus, stimulates its transcriptional activity, and enhances the expression of the E2F1 target proteins Cdc2 and Puma PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ42994

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in T cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in cellular response to ionizing radiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in determination of adult lifespan ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in execution phase of apoptosis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in execution phase of apoptosis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fibroblast apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of growth IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of IRE1-mediated unfolded protein response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cysteine-type endopeptidase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of establishment of protein localization to mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of fibroblast apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of intrinsic apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of intrinsic apoptotic signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of protein-containing complex assembly IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of release of cytochrome c from mitochondria IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of release of cytochrome c from mitochondria IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of thymocyte apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in release of cytochrome c from mitochondria IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in release of cytochrome c from mitochondria IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    colocalizes_with lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial outer membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    bcl-2-binding component 3
    Names
    p53 up-regulated modulator of apoptosis
    p53-upregulated modulator of apoptosis

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_031991.2 RefSeqGene

      Range
      6568..16943
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001127240.3 → NP_001120712.1  bcl-2-binding component 3 isoform 1

      See identical proteins and their annotated locations for NP_001120712.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) includes an alternate exon in the 5' coding region, resulting in a frameshift for the remainder of the CDS, compared to variant 2. The encoded isoform (1, also known as PUMA-gamma) has the same N-terminus but is otherwise distinct and longer, compared to isoform 2.
      Source sequence(s)
      AC008532
      Consensus CDS
      CCDS46129.1
      UniProtKB/Swiss-Prot
      Q96PG8
      Related
      ENSP00000404503.1, ENST00000449228.5

    2. NM_001127241.3 → NP_001120713.1  bcl-2-binding component 3 isoform 2

      See identical proteins and their annotated locations for NP_001120713.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes isoform 2 (also known as PUMA-beta), which includes the C-terminal BH3 domain and can localize to the mitochondria.
      Source sequence(s)
      AC008532
      Consensus CDS
      CCDS46130.1
      UniProtKB/Swiss-Prot
      Q9BXH1
      Related
      ENSP00000341155.4, ENST00000341983.8
      Conserved Domains (1) summary
      pfam15826
      Location:12 → 131
      PUMA; Bcl-2-binding component 3, p53 upregulated modulator of apoptosis

    3. NM_001127242.3 → NP_001120714.1  bcl-2-binding component 3 isoform 3

      See identical proteins and their annotated locations for NP_001120714.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two exons spanning the 5' and central coding regions, resulting in a frameshift in the 3' coding region, compared to variant 2. The encoded isoform (3, also known as PUMA-delta) has the same N-terminus but is otherwise distinct and shorter, compared to isoform 2.
      Source sequence(s)
      AC008532
      Consensus CDS
      CCDS46128.1
      UniProtKB/Swiss-Prot
      Q96PG8, Q9BXH1
      Related
      ENSP00000300880.7, ENST00000300880.11

    4. NM_014417.5 → NP_055232.1  bcl-2-binding component 3 isoform 4

      See identical proteins and their annotated locations for NP_055232.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has alternate exon structure at its 5' end and it thus differs in the 5' UTR and 5' coding region, compared to variant 2. The encoded isoform (4, also known as PUMA-alpha) has a distinct N-terminus and is longer than isoform 2. Isoform 4 also includes the C-terminal BH3 domain and can localize to the mitochondria.
      Source sequence(s)
      AC008532
      Consensus CDS
      CCDS12697.1
      UniProtKB/Swiss-Prot
      B9EGI3, O00171, Q96PG9, Q9BXH1
      UniProtKB/TrEMBL
      B4DQK3
      Related
      ENSP00000395862.2, ENST00000439096.3
      Conserved Domains (1) summary
      pfam15826
      Location:2 → 193
      PUMA; Bcl-2-binding component 3, p53 upregulated modulator of apoptosis

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      47220824..47232860 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006723141.4 → XP_006723204.1  bcl-2-binding component 3 isoform X1

      See identical proteins and their annotated locations for XP_006723204.1

      UniProtKB/Swiss-Prot
      B9EGI3, O00171, Q96PG9, Q9BXH1
      UniProtKB/TrEMBL
      B4DQK3
      Conserved Domains (1) summary
      pfam15826
      Location:2 → 193
      PUMA; Bcl-2-binding component 3, p53 upregulated modulator of apoptosis

    2. XM_047438606.1 → XP_047294562.1  bcl-2-binding component 3 isoform X1

      UniProtKB/Swiss-Prot
      B9EGI3, O00171, Q96PG9, Q9BXH1

    3. XM_011526722.3 → XP_011525024.1  bcl-2-binding component 3 isoform X2

      UniProtKB/TrEMBL
      B4DQK3
      Conserved Domains (1) summary
      pfam15826
      Location:18 → 209
      PUMA; Bcl-2-binding component 3, p53 upregulated modulator of apoptosis

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      50046144..50058334 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054320543.1 → XP_054176518.1  bcl-2-binding component 3 isoform X1

      UniProtKB/Swiss-Prot
      B9EGI3, O00171, Q96PG9, Q9BXH1

    2. XM_054320541.1 → XP_054176516.1  bcl-2-binding component 3 isoform X1

      UniProtKB/Swiss-Prot
      B9EGI3, O00171, Q96PG9, Q9BXH1

    3. XM_054320542.1 → XP_054176517.1  bcl-2-binding component 3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96PG8.2 GenPept UniProtKB/Swiss-Prot:Q96PG8
    Q9BXH1.1 GenPept UniProtKB/Swiss-Prot:Q9BXH1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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