BAK1 BCL2 antagonist/killer 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BAK1provided by HGNC
Official Full Name: BCL2 antagonist/killer 1provided by HGNC
Primary source: HGNC:HGNC:949
See related: Ensembl:ENSG00000030110 MIM:600516
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: BAK; CDN1; BCL2L7; BAK-LIKE
Summary: The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in duodenum (RPKM 20.6), small intestine (RPKM 16.4) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 6p21.31

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (33572552..33580296, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (33540323..33548072, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Data for the leukaemia risk loci BCL2-antagonist-killer 1 protein (BAK1) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) suggests deregulation of B-cell development and genetic susceptibility to precursor B-cell lymphoblastic leukemia (Pre B-ALL) [Meta-Analysis].
Title: Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk.
These results indicate that TNFalpha/CHX-induced apoptosis does not occur in Bak-/- cells, suggesting that TNFalpha/CHX-induced apoptosis is Bak-dependent but Bax-independent.
Title: CRISPR/Cas9 Knockout of Bak Mediates Bax Translocation to Mitochondria in response to TNFα/CHX-induced Apoptosis.
BAK is ubiquitinated by endogenous Parkin. Its oligomerisation restricts its ubiquitination, impairs its ability to permeabilize membranes but promotes Parkin activity.
Title: Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy.
Casp3 cleavage partially impaired the anti-apoptotic activity of Mcl-1 by reducing its mitochondrial localization and impeding its association with the permeability transition pore-forming protein Bak.
Title: Caspase cleavage of Mcl-1 impairs its anti-apoptotic activity and proteasomal degradation in non-small lung cancer cells.
The fractional cell death response reflects variable effective concentrations at the mitochondria surface of the pro-apoptotic proteins Bax/Bak.
Title: Mitochondrial origins of fractional control in regulated cell death.
BRD7 was positively correlated with BAK levels in breast cancer tissues, and the survival rate of patients with low BAK and BRD7 expression was significantly lower than that of patients with high BAK and BRD7 expression. In addition, BRD7 activated BAK promoter activity and induced BAK expression in an indirect manner.
Title: Bromodomain‑containing protein 7 sensitizes breast cancer cells to paclitaxel by activating Bcl2‑antagonist/killer protein.
we found that differential expression of BAK1, FIS1, and SFN were altered across the Barrett's disease sequence and manipulation of these genes elicited significant effects on mitochondrial membrane potential.
Title: The Mitochondrial Genes BAK1, FIS1 and SFN are Linked with Alterations in Mitochondrial Membrane Potential in Barrett's Esophagus.
Our findings suggested that ZBP-89 and Sp1 overexpression induced Bak expression in a genetic manner. Increased Bak level was associated with poor patient survival, whereas high level of Sp1 is a beneficial factor for patient survival.
Title: ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.
Study reports the proximal alpha1-alpha2 loop as a second activation site in Bak and in mitochondrial Bax.
Title: Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies.
The proapoptotic BCL-2 proteins BAX and BAK can commit a cell to its programmed death by permeabilizing the outer mitochondrial membrane and subsequent initiation of the caspase cascade. (Review)
Title: BCL-2 proteins and apoptosis: Recent insights and unknowns.

Submit: New GeneRIF Correction See all GeneRIFs (206)

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

NHGRI GWAS Catalog

Description
A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study of testicular germ cell tumor. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis identifies four new loci associated with testicular germ cell tumor. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
New gene functions in megakaryopoiesis and platelet formation. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

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
Tat	tat	HIV-1 Tat induces apoptosis of human blood-retinal barrier-associated cells by downregulation of BCL2 and upregulation of BAK, BAX, and cytochrome c in a dose-dependent manner	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH64934 (e-PCR)
- UniSTS:89222

D11S4366 (e-PCR)
- UniSTS:38127

Homology

Homologs of the BAK1 gene: The BAK1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and chicken.
Orthologs from Annotation Pipeline: 240 organisms have orthologs with human gene BAK1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
BH domain binding	IEA Inferred from Electronic Annotation more info
chaperone binding	IEA Inferred from Electronic Annotation more info
heat shock protein binding	IEA Inferred from Electronic Annotation more info
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
ion channel binding	IPI Inferred from Physical Interaction more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
molecular_function	ND No biological Data available more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
B cell apoptotic process	IEA Inferred from Electronic Annotation more info
B cell homeostasis	IEA Inferred from Electronic Annotation more info
B cell negative selection	IEA Inferred from Electronic Annotation more info
activation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	IEA Inferred from Electronic Annotation more info
aging	IEA Inferred from Electronic Annotation more info
animal organ regeneration	IEA Inferred from Electronic Annotation more info
apoptotic process	IDA Inferred from Direct Assay more info	PubMed
apoptotic process	NAS Non-traceable Author Statement more info	PubMed
apoptotic process involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
blood vessel remodeling	IEA Inferred from Electronic Annotation more info
brain development	IEA Inferred from Electronic Annotation more info
cell proliferation	IEA Inferred from Electronic Annotation more info
cellular response to UV	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to UV	ISS Inferred from Sequence or Structural Similarity more info
cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
cellular response to unfolded protein	TAS Traceable Author Statement more info	PubMed
endocrine pancreas development	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum calcium ion homeostasis	TAS Traceable Author Statement more info	PubMed
establishment or maintenance of transmembrane electrochemical gradient	IDA Inferred from Direct Assay more info	PubMed
extrinsic apoptotic signaling pathway in absence of ligand	IBA Inferred from Biological aspect of Ancestor more info	PubMed
fibroblast apoptotic process	IEA Inferred from Electronic Annotation more info
intrinsic apoptotic signaling pathway in response to DNA damage	IBA Inferred from Biological aspect of Ancestor more info	PubMed
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS Traceable Author Statement more info	PubMed
limb morphogenesis	IEA Inferred from Electronic Annotation more info
mitochondrial fusion	IEA Inferred from Electronic Annotation more info
myeloid cell homeostasis	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of endoplasmic reticulum calcium ion concentration	IEA Inferred from Electronic Annotation more info
negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
negative regulation of peptidyl-serine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of IRE1-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of calcium ion transport into cytosol	IEA Inferred from Electronic Annotation more info
positive regulation of endoplasmic reticulum unfolded protein response	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	TAS Traceable Author Statement more info
positive regulation of protein complex assembly	IDA Inferred from Direct Assay more info	PubMed
positive regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of release of cytochrome c from mitochondria	IEA Inferred from Electronic Annotation more info
post-embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
regulation of cell cycle	IEA Inferred from Electronic Annotation more info
regulation of mitochondrial membrane permeability	IDA Inferred from Direct Assay more info	PubMed
regulation of mitochondrial membrane potential	IDA Inferred from Direct Assay more info	PubMed
release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info	PubMed
release of cytochrome c from mitochondria	IGI Inferred from Genetic Interaction more info	PubMed
response to UV-C	IEA Inferred from Electronic Annotation more info
response to ethanol	IEA Inferred from Electronic Annotation more info
response to fungus	IEA Inferred from Electronic Annotation more info
response to gamma radiation	IEA Inferred from Electronic Annotation more info
response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
response to mycotoxin	IEA Inferred from Electronic Annotation more info
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
thymocyte apoptotic process	IEA Inferred from Electronic Annotation more info
vagina development	IEA Inferred from Electronic Annotation more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
BAK complex	IDA Inferred from Direct Assay more info	PubMed
Bcl-2 family protein complex	IDA Inferred from Direct Assay more info	PubMed
cytosol	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
integral component of mitochondrial outer membrane	ISS Inferred from Sequence or Structural Similarity more info
mitochondrial outer membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrial outer membrane	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
pore complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bcl-2 homologous antagonist/killer

Names: BCL2-like 7 protein; apoptosis regulator BAK; bcl-2-like protein 7; bcl2-L-7; pro-apoptotic protein BAK

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_001188.4 → NP_001179.1 bcl-2 homologous antagonist/killer

See identical proteins and their annotated locations for NP_001179.1

Status: REVIEWED

Source sequence(s)

BC004431, BM855203, CB142221, Z93017

Consensus CDS

CCDS4781.1

UniProtKB/Swiss-Prot

Q16611

UniProtKB/TrEMBL

A0A0S2Z391

Related

ENSP00000363591.3, ENST00000374467.4

Conserved Domains (1) summary

cd06845
Location:29 → 183

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

33572552..33580296 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011514779.3 → XP_011513081.1 bcl-2 homologous antagonist/killer isoform X1

See identical proteins and their annotated locations for XP_011513081.1

UniProtKB/Swiss-Prot

Q16611

UniProtKB/TrEMBL

A0A0S2Z391

Conserved Domains (1) summary

cd06845
Location:29 → 183

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...
XM_011514780.1 → XP_011513082.1 bcl-2 homologous antagonist/killer isoform X2

See identical proteins and their annotated locations for XP_011513082.1

Conserved Domains (1) summary

cd06845
Location:2 → 124

Bcl-2_like; Apoptosis regulator proteins of the Bcl-2 family, named after B-cell lymphoma 2. This alignment model spans what have been described as Bcl-2 homology regions BH1, BH2, BH3, and BH4. Many members of this family have an additional C-terminal transmembrane ...