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

Gene ID: 27113, updated on 27-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
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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
  • 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

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