BBC3 BCL2 binding component 3 [Homo sapiens] - Gene

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Summary

Official Symbol: BBC3provided by HGNC
Official Full Name: BCL2 binding component 3provided by HGNC
Primary source: HGNC:17868
See related: Ensembl:ENSG00000105327; HPRD:16165; MIM:605854
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; FLJ42994
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]

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Genomic context

Location :: 19q13.3-q13.4

Sequence :: Chromosome: 19; NC_000019.9 (47724079..47736023, complement)

See BBC3 in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The PUMA expression induced by stretch is mediated by IFN-gamma, JNK, and IRF-1 pathways.
Title: Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells.
Smad4 suppresses the PAK1, which promotes the PUMA destabilization
Title: Novel tumor suppressive function of Smad4 in serum starvation-induced cell death through PAK1-PUMA pathway.
p21 prevents Puma and its downstream effector Bax from triggering the mitochondrial apoptotic pathway.
Title: Serum-nutrient starvation induces cell death mediated by Bax and Puma that is counteracted by p21 and unmasked by Bcl-x(L) inhibition.
Puma is a major regulator of memory B lymphocyte survival and therefore a key molecule in the control of the immune response.
Title: Regulation of memory B-cell survival by the BH3-only protein Puma.
In mice and humans, colon inflammation induces apoptosis of intestinal epithelial cells via p53-dependent and - independent mechanisms; PUMA also activates an intrinsic apoptosis pathway associated with colitis.
Title: p53 and PUMA independently regulate apoptosis of intestinal epithelial cells in patients and mice with colitis.
Micro RNA miR-296-5p takes part in the regulation of PUMA expression during hepatic lipoapoptosis.
Title: A role for miR-296 in the regulation of lipoapoptosis by targeting PUMA.
Puma mRNA expression is significantly correlated with prognostic factors, and may be a prognostic marker of chronic lymphocytic leukemia.
Title: [Detection of puma mRNA levels by real-time quantitative RT-PCR in chronic lymphocytic leukemia and its clinical significance].
PUMA induction contributes to the pathogenesis of colitis by promoting IEC apoptosis
Title: PUMA-mediated intestinal epithelial apoptosis contributes to ulcerative colitis in humans and mice.
Expression of p53-inducible BH3-only apoptotic proteins Puma and Noxa was elevated and large activation of executive caspases was observed.
Title: Decitabine-induced apoptosis is derived by Puma and Noxa induction in chronic myeloid leukemia cell line as well as in PBL and is potentiated by SAHA.
The phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival.
Title: Phosphorylation of Puma modulates its apoptotic function by regulating protein stability.

Submit: New GeneRIF Correction See all (74)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 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 Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
AAK39543.1		BCL2	BIND	PubMed	PUMA-beta interacts with Bcl-2.
NP_055232.1	NP_620116.1	BAX	BIND	PubMed	Bax interacts with PUMA.
NP_055232.1	NP_000624.1	BCL2	BIND	PubMed	Puma interacts with Bcl-2.
NP_055232.1		BCL2	BIND	PubMed	PUMA interacts with Bcl-2.
NP_055232.1		BCL2	BIND	PubMed	PUMA-alpha interacts with Bcl-2.
NP_055232.1	NP_004040.1	BCL2A1	BIND	PubMed	Puma interacts with A1. This interaction was modelled on a demonstrated interaction between human Puma and mouse A1.
NP_055232.1	NP_612815.1	BCL2L1	BIND	PubMed	Puma interacts with Bcl-XL.
NP_055232.1	NP_612815.1	BCL2L1	BIND	PubMed	PUMA interacts with Bcl-xL.
NP_055232.1	NP_612815.1	BCL2L1	BIND	PubMed	Bcl-XL interacts with Puma. This interaction was modelled on a demonstrated interaction between Bcl-XL from an unspecified species and human Puma.
NP_055232.1	NP_004041.1	BCL2L2	BIND	PubMed	Puma interacts with Bcl-w.
NP_055232.1	NP_001708.2	BNC1	BIND	PubMed	Puma interacts with Mcl-1. This interaction was modelled on a demonstrated interaction between human Puma and mouse Mcl-1.
NP_055232.1		MCL1	BIND	PubMed	Mcl-1 interacts with Puma. This interaction was modelled on a demonstrated interaction between Mcl-1 from an unspecified species and human Puma.
Q9BXH1	Q07814	BAX	HPRD	PubMed
Q9BXH1	P10415	BCL2	HPRD	PubMed
Q9BXH1	Q16548	BCL2A1	HPRD	PubMed
Q9BXH1	Q07817	BCL2L1	HPRD	PubMed
Q9BXH1	Q92843	BCL2L2	HPRD	PubMed
Q9BXH1	Q07820	MCL1	HPRD	PubMed
BioGRID:118009	BioGRID:107068	BCL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118009	BioGRID:107070	BCL2L1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118009	BioGRID:110338	MCL1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Function	Evidence Code	Pubs
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	ISS Inferred from Sequence or Structural Similarity more info
activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
activation of pro-apoptotic gene products	TAS Traceable Author Statement more info
apoptotic process	IDA Inferred from Direct Assay more info	PubMed
apoptotic process	TAS Traceable Author Statement more info
cellular response to hypoxia	IEP Inferred from Expression Pattern more info
determination of adult lifespan	ISS Inferred from Sequence or Structural Similarity more info
induction of apoptosis	IDA Inferred from Direct Assay more info	PubMed
induction of apoptosis by intracellular signals	TAS Traceable Author Statement more info
negative regulation of growth	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein homooligomerization	IDA Inferred from Direct Assay more info
positive regulation of release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info	PubMed
positive regulation of release of cytochrome c from mitochondria	IGI Inferred from Genetic Interaction more info
positive regulation of thymocyte apoptosis	ISS Inferred from Sequence or Structural Similarity more info
protein insertion into mitochondrial membrane involved in induction of apoptosis	IDA Inferred from Direct Assay more info	PubMed
reduction of endoplasmic reticulum calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info	PubMed
release of sequestered calcium ion into cytosol	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
mitochondrial outer membrane	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: bcl-2-binding component 3

Names: bcl-2-binding component 3; p53 up-regulated modulator of apoptosis

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NCBI Reference Sequences (RefSeq)

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

NG_031991.1 RefSeqGene

Range

5001..16945

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

AA887822, AF354654, BG258126, U82987

Consensus CDS

CCDS46129.1

UniProtKB/TrEMBL

E9PAW3

UniProtKB/Swiss-Prot

Q9BXH1

Related

ENSP00000404503, ENST00000449228
NM_001127241.2 → NP_001120713.1 bcl-2-binding component 3 isoform 2

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)

AA887822, AF354655, BG258126, U82987

Consensus CDS

CCDS46130.1

UniProtKB/Swiss-Prot

Q9BXH1

Related

ENSP00000341155, ENST00000341983
NM_001127242.2 → NP_001120714.1 bcl-2-binding component 3 isoform 3

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)

AA887822, AF354656, BG258126, U82987

Consensus CDS

CCDS46128.1

UniProtKB/TrEMBL

Q96PG8

UniProtKB/Swiss-Prot

Q9BXH1

Related

ENSP00000300880, ENST00000300880
NM_014417.4 → NP_055232.1 bcl-2-binding component 3 isoform 4

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)

AA887822, AF332558, BG258126, U82987

Consensus CDS

CCDS12697.1

UniProtKB/Swiss-Prot

Q9BXH1

Related

ENSP00000395862, ENST00000439096

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p5 Primary Assembly

Range

47724079..47736023, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

44148994..44171276, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008532.7 (74595..84962)	None
genomic	CH471126.1	EAW57465.1
		EAW57466.1
		EAW57467.1
mRNA	AA887822.1	None
mRNA	AF332558.1	AAK31316.1
mRNA	AF354654.1	AAK39542.1
mRNA	AF354655.1	AAK39543.1
mRNA	AF354656.1	AAK39544.1
mRNA	AK124984.1	None
mRNA	AK298837.1	BAG60965.1
mRNA	BC136481.1	AAI36482.1
mRNA	BG258126.1	None
mRNA	U82987.1	AAB51243.2