BAX (BCL2 associated X, apoptosis regulator)

Gene

• Entrez ID: 581
• Gene name: BCL2 associated X, apoptosis regulator
• Gene symbol: BAX
• Synonyms: BCL2L4
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Dec 2019]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs398122513	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant, intron variant
rs398122840	GGGGGGG>-,GGGGGG,GGGGGGGG	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, initiator codon variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016249	hsa-miR-504-5p	qRT-PCR	20542001
MIRT019436	hsa-miR-148b-3p	Microarray	17612493
MIRT023402	hsa-miR-122-5p	Microarray	17612493
MIRT023402	hsa-miR-122-5p	Western blot	18692484
MIRT023989	hsa-miR-1-3p	Proteomics;Microarray	18668037
MIRT028651	hsa-miR-30a-5p	Proteomics	18668040
MIRT044018	hsa-miR-365a-3p	CLASH	23622248
MIRT044018	hsa-miR-365a-3p	Microarray, Western blot	24216611
MIRT437798	hsa-miR-128-3p	Luciferase reporter assay, qRT-PCR, Western blot	23526655
MIRT438124	hsa-miR-214-3p	Luciferase reporter assay	23408966
MIRT438137	hsa-miR-766-3p	Flow, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	24356076
MIRT438317	hsa-miR-298	Luciferase reporter assay, qRT-PCR, Western blot	26064232
MIRT731976	hsa-miR-7-5p	Luciferase reporter assay	27158385
MIRT731977	hsa-miR-34a-5p	Luciferase reporter assay, Western blot	27610823
MIRT733283	hsa-miR-181a-5p	Luciferase reporter assay, Western blot	26028030
MIRT733878	hsa-miR-15b-5p	Western blot	27499071
MIRT734355	hsa-miR-148a-3p	Luciferase reporter assay, qRT-PCR, Western blot	27261578

Transcription factors

Transcription factor	Regulation	Reference
AATF	Repression	22909821
ABL1	Activation	11753601
ATM	Activation	16214353
DMAP1	Unknown	24559687
ELL	Repression	15851483
ERCC2	Activation	22387547
ETS1	Repression	17213822
GFI1	Repression	17213822
HIF1A	Activation	15706354
ING1	Activation	15662138;16325212
ING4	Activation	20707719
MLLT10	Repression	15851483
MLLT3	Repression	15851483
MYCN	Activation	19885598
NFKB1	Repression	18158998
NFKB1	Unknown	20056115
NR3C1	Activation	17496926
PAX5	Activation	22105368
PER1	Repression	19675098
PML	Activation	16007146
RELA	Repression	18158998
RELA	Unknown	20056115
SP1	Unknown	11278953
STAT1	Unknown	17346710
TP53	Activation	10101800;10566557;15851483;17280505;17693666;18172861;20673369;22532570;22732402;9000137
TP53	Unknown	10559267;11278953;12851404;15988033;19067706;21859835
TP63	Activation	16007146
TP73	Unknown	19067706
WWTR1	Activation	22470139

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001541	Process	Ovarian follicle development	IEA
GO:0001764	Process	Neuron migration	IEA
GO:0001777	Process	T cell homeostatic proliferation	IEA
GO:0001782	Process	B cell homeostasis	IEA
GO:0001783	Process	B cell apoptotic process	IDA	15214043, 16424160
GO:0001822	Process	Kidney development	IEA
GO:0001836	Process	Release of cytochrome c from mitochondria	IBA	21873635
GO:0001836	Process	Release of cytochrome c from mitochondria	IDA	9843949, 16199525, 17052454, 25609812
GO:0001844	Process	Protein insertion into mitochondrial membrane involved in apoptotic signaling pathway	TAS
GO:0001974	Process	Blood vessel remodeling	IEA
GO:0002262	Process	Myeloid cell homeostasis	IEA
GO:0002352	Process	B cell negative selection	IEA
GO:0002358	Process	B cell homeostatic proliferation	IEA
GO:0002904	Process	Positive regulation of B cell apoptotic process	IEA
GO:0005515	Function	Protein binding	IPI	9027312, 9111042, 9388232, 9463381, 9843949, 10753914, 11161816, 11278245, 11571294, 11574543, 12732850, 12925958, 14730312, 14752512, 14963330, 15205477, 15901672, 16113678, 16151013, 16439990, 16509771, 16608847, 16645094, 17123957, 17289999, 17485524, 17525735, 17606912, 17635912
GO:0005634	Component	Nucleus	IDA	12925958
GO:0005634	Component	Nucleus	IMP	15102863
GO:0005635	Component	Nuclear envelope	IDA	12925958
GO:0005737	Component	Cytoplasm	IDA	16302269, 29531808
GO:0005739	Component	Mitochondrion	IDA	11912183, 15102863, 15705586, 16199525, 17823127, 19767770, 25609812
GO:0005741	Component	Mitochondrial outer membrane	IBA	21873635
GO:0005741	Component	Mitochondrial outer membrane	IDA	29531808
GO:0005741	Component	Mitochondrial outer membrane	TAS
GO:0005757	Component	Mitochondrial permeability transition pore complex	IDA	9843949
GO:0005783	Component	Endoplasmic reticulum	IDA	16424160
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	16424160
GO:0005829	Component	Cytosol	IDA	11912183, 12925958, 15102863, 15705586, 17823127, 19767770
GO:0005829	Component	Cytosol	TAS
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0006687	Process	Glycosphingolipid metabolic process	IEA
GO:0006808	Process	Regulation of nitrogen utilization	IEA
GO:0006915	Process	Apoptotic process	IDA	9660918, 17428862
GO:0006915	Process	Apoptotic process	IMP	9531611
GO:0006915	Process	Apoptotic process	NAS	9920818
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	11912183
GO:0006919	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	11350920
GO:0006977	Process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	TAS
GO:0007281	Process	Germ cell development	IEA
GO:0008053	Process	Mitochondrial fusion	IBA	21873635
GO:0008053	Process	Mitochondrial fusion	IDA	14769861
GO:0008289	Function	Lipid binding	IDA	14522999
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IC	16199525
GO:0008630	Process	Intrinsic apoptotic signaling pathway in response to DNA damage	IBA	21873635
GO:0008635	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	IDA	15214043
GO:0008637	Process	Apoptotic mitochondrial changes	IDA	9843949
GO:0009566	Process	Fertilization	IEA
GO:0009636	Process	Response to toxic substance	IDA	16307838
GO:0009651	Process	Response to salt stress	IEA
GO:0010248	Process	Establishment or maintenance of transmembrane electrochemical gradient	IDA	9843949
GO:0010332	Process	Response to gamma radiation	IEA
GO:0010917	Process	Negative regulation of mitochondrial membrane potential	IDA	16751333
GO:0015267	Function	Channel activity	IBA	21873635
GO:0015267	Function	Channel activity	IDA	9219694
GO:0016020	Component	Membrane	HDA	19946888
GO:0016032	Process	Viral process	IEA
GO:0021854	Process	Hypothalamus development	IEA
GO:0021987	Process	Cerebral cortex development	IEA
GO:0030544	Function	Hsp70 protein binding	IEA
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	9111042, 19805544
GO:0032091	Process	Negative regulation of protein binding	IDA	9388232
GO:0032469	Process	Endoplasmic reticulum calcium ion homeostasis	TAS	18309324
GO:0032471	Process	Negative regulation of endoplasmic reticulum calcium ion concentration	IEA
GO:0032976	Process	Release of matrix enzymes from mitochondria	IDA	9843949
GO:0033137	Process	Negative regulation of peptidyl-serine phosphorylation	IEA
GO:0033599	Process	Regulation of mammary gland epithelial cell proliferation	IEA
GO:0034620	Process	Cellular response to unfolded protein	TAS	22013210
GO:0034644	Process	Cellular response to UV	IEA
GO:0035234	Process	Ectopic germ cell programmed cell death	IEA
GO:0042475	Process	Odontogenesis of dentin-containing tooth	IEA
GO:0042802	Function	Identical protein binding	IPI	10620504, 14963330, 16113678, 17024184, 17289999, 17668322, 18547146, 18835031, 19062087, 19074440, 19767770, 20360684, 20541605, 20850011, 22198199, 23374347
GO:0042803	Function	Protein homodimerization activity	IBA	21873635
GO:0042803	Function	Protein homodimerization activity	IDA	16608847
GO:0042981	Process	Regulation of apoptotic process	IDA	25609812
GO:0042981	Process	Regulation of apoptotic process	TAS
GO:0043065	Process	Positive regulation of apoptotic process	IBA	21873635
GO:0043065	Process	Positive regulation of apoptotic process	IDA	16751333, 17464193
GO:0043065	Process	Positive regulation of apoptotic process	IMP	17289999
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043525	Process	Positive regulation of neuron apoptotic process	IDA	15637643
GO:0043653	Process	Mitochondrial fragmentation involved in apoptotic process	IDA	12499352
GO:0045136	Process	Development of secondary sexual characteristics	IEA
GO:0046666	Process	Retinal cell programmed cell death	IEA
GO:0046930	Component	Pore complex	IDA	9219694
GO:0046982	Function	Protein heterodimerization activity	IBA	21873635
GO:0046982	Function	Protein heterodimerization activity	IPI	9111042
GO:0048087	Process	Positive regulation of developmental pigmentation	IEA
GO:0048147	Process	Negative regulation of fibroblast proliferation	IEA
GO:0048515	Process	Spermatid differentiation	IEA
GO:0048597	Process	Post-embryonic camera-type eye morphogenesis	IEA
GO:0048678	Process	Response to axon injury	IEA
GO:0048873	Process	Homeostasis of number of cells within a tissue	IEA
GO:0051087	Function	Chaperone binding	IEA
GO:0051281	Process	Positive regulation of release of sequestered calcium ion into cytosol	IEA
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0051434	Function	BH3 domain binding	IDA	21199865
GO:0051434	Function	BH3 domain binding	IPI	15705586, 17052454
GO:0051881	Process	Regulation of mitochondrial membrane potential	IDA	9843949
GO:0060011	Process	Sertoli cell proliferation	IEA
GO:0060041	Process	Retina development in camera-type eye	IEA
GO:0060058	Process	Positive regulation of apoptotic process involved in mammary gland involution	IEA
GO:0060068	Process	Vagina development	IEA
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP	16645094
GO:0070059	Process	Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	TAS	22934019
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070242	Process	Thymocyte apoptotic process	IEA
GO:0070584	Process	Mitochondrion morphogenesis	IEA
GO:0071944	Component	Cell periphery	IDA	21803450
GO:0072332	Process	Intrinsic apoptotic signaling pathway by p53 class mediator	IEA
GO:0090200	Process	Positive regulation of release of cytochrome c from mitochondria	IDA	14963330
GO:0090200	Process	Positive regulation of release of cytochrome c from mitochondria	IMP	21262771
GO:0097136	Component	Bcl-2 family protein complex	IDA	21199865
GO:0097144	Component	BAX complex	IDA	14522999, 17024184, 19074440, 19767770, 20541605, 20850011
GO:0097145	Component	BAK complex	IDA	16113678
GO:0097190	Process	Apoptotic signaling pathway	IDA	16424160
GO:0097191	Process	Extrinsic apoptotic signaling pathway	IDA	15214043
GO:0097192	Process	Extrinsic apoptotic signaling pathway in absence of ligand	IBA	21873635
GO:0097193	Process	Intrinsic apoptotic signaling pathway	IDA	9219694, 16462759
GO:0097296	Process	Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IEA
GO:0098586	Process	Cellular response to virus	IDA	25609812
GO:1900103	Process	Positive regulation of endoplasmic reticulum unfolded protein response	IMP	16645094
GO:1901030	Process	Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	TAS
GO:1902262	Process	Apoptotic process involved in blood vessel morphogenesis	IEA
GO:1902263	Process	Apoptotic process involved in embryonic digit morphogenesis	IEA
GO:1902445	Process	Regulation of mitochondrial membrane permeability involved in programmed necrotic cell death	IEA
GO:1902512	Process	Positive regulation of apoptotic DNA fragmentation	IMP	11350920
GO:1903896	Process	Positive regulation of IRE1-mediated unfolded protein response	TAS	22013210
GO:1990117	Process	B cell receptor apoptotic signaling pathway	IDA	15214043
GO:2001234	Process	Negative regulation of apoptotic signaling pathway	IEA
GO:2001244	Process	Positive regulation of intrinsic apoptotic signaling pathway	IMP	14963330, 21199865, 21262771

Other IDs

• MIM: 600040
• HGNC: 959
• e!Ensembl: ENSG00000087088

Protein

• UniProt ID: Q07812
• Protein name: Apoptosis regulator BAX (Bcl-2-like protein 4) (Bcl2-L-4)
• Protein function: Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM) (PubMed:21458670). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.
• PDB: 1F16, 2G5B, 2K7W, 2LR1, 3PK1, 3PL7, 4BD2, 4BD6, 4BD7, 4BD8, 4BDU, 4S0O, 4S0P, 4UF2, 4ZIE, 4ZIF, 4ZIG, 4ZIH, 4ZII, 5W5X, 5W5Z, 5W60, 5W61, 6EB6, 6L8V, 6L95, 6TRR, 6XY6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00452	Bcl-2	63 → 158	Apoptosis regulator proteins, Bcl-2 family	Family

• Sequence:

  MDGSGEQPRGGGPTSSEQIMKTGALLLQGFIQDRAGRMGGEAPELALDPVPQDASTKKLS
  ECLKRIGDELDSNMELQRMIAAVDTDSPREVFFRVAADMFSDGNFNWGRVVALFYFASKL
  VLKALCTKVPELIRTIMGWTLDFLRERLLGWIQDQGGWDGLLSYFGTPTWQTVTIFVAGV
  LTASLTIWKKMG

• Sequence length: 192