Bcl-2 homologous antagonist killer

BCL2-antagonist/killer 1
PDB rendering based on 2ims.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BXL, 2IMS, 2IMT, 2JBY, 2JCN, 2M5B, 2XPX, 2YV6, 3I1H, 3QBR
Identifiers
Symbols	BAK1 ; BAK; BAK-LIKE; BCL2L7; CDN1
External IDs	OMIM: 600516 MGI: 1097161 HomoloGene: 917 ChEMBL: 5609 GeneCards: BAK1 Gene
Gene ontology Molecular function • protein binding • heat shock protein binding • identical protein binding • protein homodimerization activity • metal ion binding • protein heterodimerization activity • chaperone binding • BH domain binding Cellular component • mitochondrion • mitochondrial outer membrane • endoplasmic reticulum • cytosol • integral component of mitochondrial outer membrane • pore complex Biological process • B cell homeostasis • B cell apoptotic process • release of cytochrome c from mitochondria • blood vessel remodeling • myeloid cell homeostasis • B cell negative selection • apoptotic process • brain development • aging • mitochondrial fusion • cell proliferation • negative regulation of cell proliferation • intrinsic apoptotic signaling pathway in response to DNA damage • activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c • response to fungus • response to mycotoxin • response to UV-C • establishment or maintenance of transmembrane electrochemical gradient • response to gamma radiation • positive regulation of calcium ion transport into cytosol • negative regulation of gene expression • response to organic cyclic compound • endocrine pancreas development • organ regeneration • endoplasmic reticulum calcium ion homeostasis • negative regulation of endoplasmic reticulum calcium ion concentration • negative regulation of peptidyl-serine phosphorylation • cellular response to UV • limb morphogenesis • response to drug • response to hydrogen peroxide • positive regulation of apoptotic process • regulation of protein homodimerization activity • regulation of protein heterodimerization activity • fibroblast apoptotic process • response to ethanol • positive regulation of proteolysis • regulation of mitochondrial membrane permeability • post-embryonic camera-type eye morphogenesis • regulation of cell cycle • regulation of mitochondrial membrane potential • vagina development • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • thymocyte apoptotic process • cellular response to mechanical stimulus • positive regulation of release of cytochrome c from mitochondria • apoptotic signaling pathway • extrinsic apoptotic signaling pathway in absence of ligand • intrinsic apoptotic signaling pathway • activation of cysteine-type endopeptidase activity • positive regulation of endoplasmic reticulum unfolded protein response • positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway • apoptotic process involved in patterning of blood vessels Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	578	12018
Ensembl	ENSG00000030110	ENSMUSG00000057789
UniProt	Q16611	O08734
RefSeq (mRNA)	NM_001188	NM_007523
RefSeq (protein)	NP_001179	NP_031549
Location (UCSC)	Chr 20: 31.28 – 31.28 Mb	Chr 17: 27.02 – 27.03 Mb
PubMed search

Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene.^[1][2] BAK1 orthologs ^[3] have been identified in most mammals for which complete genome data are available.

The BAK protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. Dysregulation of the BAK gene has been implicated in human gastrointestinal cancers, indicating that the gene plays a part in the pathogenesis of some cancers.^[4]

Overview of signal transduction pathways involved in apoptosis.

Function

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.^[5]

BAK1 gene variation

Recently, one study of the role of genetics in abdominal aortic aneurism (AAA) showed that different BAK1 variants can exist in both diseased and nondiseased AA tissues compared to matching blood samples.^[6] Since its publication, this observation has raised many discussions among scientific community because it seems to jeopardize the current paradigm that all cells have the same genomic DNA. However, BAK1 gene variants in different tissues may be easily explained by the expression of BAK1 gene on chromosome 6 and one its edited copies on chromosome 20. This conjecture reconciles both the current paradigm and the observation of BAK1 gene variation in different tissues.^[7][8] However, the authors of the BAK1 gene variations original article have published a response.^[7]

Interactions

BAK1 has been shown to interact with:

• BCL2-like 1,^{[9][10][11][12][13]}
• Bcl-2,^[14][15]
• MCL1,^{[12][16][17][18]} and
• P53^[16]

References

Further reading

PDB gallery 2ims: The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site  2imt: The X-ray Structure of a Bak Homodimer Reveals an Inhibitory Zinc Binding Site  2jcn: THE CRYSTAL STRUCTURE OF BAK1 - A MITOCHONDRIAL APOPTOSIS REGULATOR