Search TCDB: (?)
TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


1.A.21.1.2
The mitochondrial apoptosis-inducing channel-forming protein, BAX.  The C-terminal helix mediates membrane binding and pore formation (Garg et al. 2012). BAX pores are large enough to allow cytochrome c release and it activates the mitochondrial permeabilty transition pore; both play a role in programmed cell death, but the latter is quantitatively more important (Gómez-Crisóstomo et al. 2013). Bax functions like a holin when expressed in bacteria (Pang et al. 2011).  Bax (and likely Bak) dimers assemble into oligomers with an even number of molecules that fully or partially delineate pores of different sizes to permeabilize the mitochondrial outer membrane (MOM) during apoptosis (Cosentino and García-Sáez 2016). The membrane domain of Bax interacts with other members of the Bcl-2 family to form hetero-oligomers (Andreu-Fernández et al. 2017).  Uren et al. 2017 reviewed how clusters of dimers and their lipid-mediated interactions provide a molecular explanation for the heterogeneous assemblies of Bak and Bax observed during apoptosis. After BAK/BAX activation and cytochrome c loss, the mitochondrial network breaks down, and large BAK/BAX pores appear in the outer membrane. These macropores allow the inner membrane an outlet through which it herniated, carrying with it mitochondrial matrix components including the mitochondrial genome (McArthur et al. 2018). The core/dimerization domain of Bax and Bak is water exposed with only helices 4 and 5 in membrane contact, whereas the piercing/latch domain is in peripheral membrane contact, with helix 9 being transmembrane (Bleicken et al. 2018). The mechanism of the membrane disruption and pore-formation by the BAX C-terminal TMS has been investigated (Jiang and Zhang 2019).  Bax membrane permeabilization results from oligomerization of transmembrane monomers (Annis et al. 2005). Bax localization and apoptotic activity are conformationally controled by Pro168 (Schinzel et al. 2004).

Accession Number:Q07812
Protein Name:Apoptosis regulator BAX
Length:192
Molecular Weight:21184.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Cytoplasm1
Substrate molecule, macromolecule, cytochrome c

Cross database links:

DIP: DIP-232N
RefSeq: NP_004315.1    NP_620116.1    NP_620118.1    NP_620119.2   
Entrez Gene ID: 581   
Pfam: PF00452   
OMIM: 600040  gene
KEGG: hsa:581   

Gene Ontology

GO:0005829 C:cytosol
GO:0005789 C:endoplasmic reticulum membrane
GO:0005741 C:mitochondrial outer membrane
GO:0005757 C:mitochondrial permeability transition pore ...
GO:0051434 F:BH3 domain binding
GO:0008289 F:lipid binding
GO:0046982 F:protein heterodimerization activity
GO:0042803 F:protein homodimerization activity
GO:0008635 P:activation of caspase activity by cytochrome c
GO:0001783 P:B cell apoptosis
GO:0006922 P:cleavage of lamin
GO:0006309 P:DNA fragmentation involved in apoptosis
GO:0010248 P:establishment or maintenance of transmembra...
GO:0008624 P:induction of apoptosis by extracellular sig...
GO:0008629 P:induction of apoptosis by intracellular sig...
GO:0046674 P:induction of retinal programmed cell death
GO:0043653 P:mitochondrial fragmentation during apoptosis
GO:0008053 P:mitochondrial fusion
GO:0008634 P:negative regulation of survival gene produc...
GO:0030264 P:nuclear fragmentation during apoptosis
GO:0043525 P:positive regulation of neuron apoptosis
GO:0051260 P:protein homooligomerization
GO:0051881 P:regulation of mitochondrial membrane potential
GO:0043497 P:regulation of protein heterodimerization ac...
GO:0043496 P:regulation of protein homodimerization acti...
GO:0001836 P:release of cytochrome c from mitochondria
GO:0032976 P:release of matrix enzymes from mitochondria
GO:0009636 P:response to toxin
GO:0006927 P:transformed cell apoptosis

References (17)

[1] “Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.”  Oltvai Z.N.et.al.   8358790
[2] “Mapping of the human BAX gene to chromosome 19q13.3-q13.4 and isolation of a novel alternatively spliced transcript, BAX delta.”  Apte S.S.et.al.   7607685
[3] “Identification and characterization of baxepsilon, a novel bax variant missing the BH2 and the transmembrane domains.”  Shi B.et.al.   9920818
[4] “Characterization of Bax-sigma, a cell death-inducing isoform of Bax.”  Schmitt E.et.al.   10772918
[5] “The expression of a new variant of the pro-apoptotic molecule Bax, Baxpsi, is correlated with an increased survival of glioblastoma multiforme patients.”  Cartron P.F.et.al.   11912183
[6] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[7] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[8] “Bax mutations in cell lines derived from hematological malignancies.”  Meijerink J.P.P.et.al.   7475270
[9] “A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.”  Chittenden T.et.al.   8521816
[10] “Conformation of the Bax C-terminus regulates subcellular location and cell death.”  Nechushtan A.et.al.   10228148
[11] “Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates with Bax.”  Cuddeback S.M.et.al.   11259440
[12] “Humanin peptide suppresses apoptosis by interfering with Bax activation.”  Guo B.et.al.   12732850
[13] “JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins.”  Tsuruta F.et.al.   15071501
[14] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330
[15] “Structure of Bax: coregulation of dimer formation and intracellular localization.”  Suzuki M.et.al.   11106734
[16] “Elucidation of some Bax conformational changes through crystallization of an antibody-peptide complex.”  Peyerl F.W.et.al.   16946732
[17] “Hematopoietic malignancies demonstrate loss-of-function mutations of BAX.”  Meijerink J.P.P.et.al.   9531611
Structure:
1F16   2G5B   2K7W   2LR1   3PK1   3PL7   4BD2   4BD6   4BD7   4BD8   [...more]

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence 
1:	MDGSGEQPRG GGPTSSEQIM KTGALLLQGF IQDRAGRMGG EAPELALDPV PQDASTKKLS 
61:	ECLKRIGDEL DSNMELQRMI AAVDTDSPRE VFFRVAADMF SDGNFNWGRV VALFYFASKL 
121:	VLKALCTKVP ELIRTIMGWT LDFLRERLLG WIQDQGGWDG LLSYFGTPTW QTVTIFVAGV 
181:	LTASLTIWKK MG