TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.A.21.1.1









Apoptosis regulator Bcl-X(L) of 233 aas.  Also called Bcl2-like protein 1, isoform 1. Membrane insertion of the soluble form has been characterized (Vargas-Uribe et al. 2013).  The cytosolic domain of Bcl-2 forms small pores in the mitochondrial outer membrane (Peng et al. 2009).

Eukaryota
Metazoa
Bcl-X(L) of Homo sapiens
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).

Eukaryota
Metazoa
BAX of Homo sapiens (Q07812)
1.A.21.1.3









The mitochondrial apoptosis-inducing channel-forming protein, BAK. 3-D structures are known (2IMT_A).  Functions like a holin when expressed in bacteria (Pang et al. 2011).  Formation of the apoptotic pore involves a flexible C-terminal domain (Iyer et al. 2015). 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). BAK is a C-tail-anchored mitochondrial outer membrane protein (Setoguchi et al. 2006). BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization (Hosoi 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 herniates, carrying with it mitochondrial matrix components including the mitochondrial genome (McArthur et al. 2018).

Eukaryota
Metazoa
BAK of Homo sapiens (Q16611). 
1.A.21.1.4









The BH3-only (Mcl-1) protein (mediates apoptosis). (3-d strucure known)

Eukaryota
Metazoa
BH3-only of Homo sapiens (B4DG83)
1.A.21.1.5









Pro-survival Bcl-w protein.  Binds the BH3-only protein Bop to inhibit Bop-induced apoptosis (Zhang et al. 2012).  The structure is known (PDB# 1MK3).

Eukaryota
Metazoa
Bcl-w of Homo sapiens
1.A.21.1.6









Bcl-XL of 289 aas, a C-tail-anchored mitochondrial outer membrane protein (Setoguchi et al. 2006). The BH4 domain of Bcl-XL, but not that of Bcl-2, selectively targets VDAC1 and inhibits apoptosis by decreasing VDAC1-mediated Ca2+ uptake into mitochondria (Monaco et al. 2015). The ER-mitochondrion interface is a critical cell-signaling junction whereby Bcl-xL dynamically interacts with type 3 inositol 1,4,5-trisphosphate receptors (IP3R3) to coordinate mitochondrial Ca2+ transfer and alters cellular metabolism in order to increase the cells' bioenergetic capacity, particularly during periods of stress (Williams et al. 2016).

Eukaryota
Metazoa
Bcl-XL of Xenopus laevis (African clawed frog)
1.A.21.1.7









Pore-forming Bcl-2-related ovarian killer protein, Bok of 212 aas and 2 or more predicted TMSs.  Apoptosis regulator that functions through different apoptotic signaling pathways (Einsele-Scholz et al. 2016, Yakovlev et al. 2004, Jääskeläinen et al. 2010). The transmembrane-domain contributes to the pro-apoptotic function and interactions of Bok with other proteins (Stehle et al. 2018).

 

Eukaryota
Metazoa
Bok of Homo sapiens
1.A.21.1.8









Bcl-2-like death executioner of 172 aas and 2 TMSs, one in the middle of the protein and one at the C-terminus. 

Eukaryota
Metazoa
Death executioner of Locusta migratoria (migratory locust)
1.A.21.1.9









Uncharacterized protein of 224 aas and 2 TMSs.

Eukaryota
Metazoa
UP of Nematostella vectensis (Starlet sea anemone)
1.A.21.1.10









Bcl-2 apoptosis regulator of 239 aas and 2 TMSs.  It suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. It regulates cell death by controlling the mitochondrial membrane permeability and appears to function in a feedback loop system with caspases. It inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1), and it may attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (Bruey et al. 2007).

Eukaryota
Metazoa
Bcl-2 of Homo sapiens
1.A.21.1.11









Apoptosis regulator BAX-like isoform X2, of 198 aas and 2 or 3 TMSs.

Eukaryota
Metazoa
BAX-like protein of Perca flavescens (yellow perch)
1.A.21.1.12









The Cell Death (CED-9) protein (Siskind et al., 2008)
Eukaryota
Metazoa
CED-9 of Caenorhabditis elegans (P41958)
1.A.21.1.13









BCL2-associated X protein, BAX, of 204 aas and 1 C-terminal TMS, possibly with a second internal TMS. The expression of the ccBAX gene is down-regulated by the miR-124 miRNA in silver crucian carp upon cyprinid herpesvirus 2 infection (Yu et al. 2021).

Eukaryota
Opisthokonta
BAX of Carassius gibelio (silver crucian carp)
1.A.21.2.1









BH3-interacting domain death agonist of 199 aas and 2 or 3 putative TMSs.

Eukaryota
Metazoa
BH3-interacting agonist of Tachysurus fulvidraco (yellow catfish)
1.A.21.2.2









BH3-interacting domain death agonist-like isoform X3 of 204 aas and 2 or 3 TM

Eukaryota
Metazoa
Death agonists of Boleophthalmus pectinirostris (great blue-spotted mudskipper)
1.A.21.2.3









Uncharacterized protein of 207 aas and 2 or 3 TMSs.

Eukaryota
Metazoa
UP of Lepisosteus oculatus (spotted gar)
1.A.21.2.4









BH3-interacting domain death agonist isoform 2, BID, of 195 aas and 2 or 3 TMSs. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, the transmembrane domain of diphtheria toxin, and the N-terminal domain of delta-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. Oh et al. 2005 showed that helices 6-8 maintain an alpha-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation.

Eukaryota
Metazoa
BID of Homo sapiens
1.A.21.2.5









BH3-interacting domain death agonist isoform X3 of 241 aas and 2 or 3 TM

Eukaryota
Metazoa
Death agonist of Phocoena sinus