| Literature References | 1. HUNOT, S. AND FLAVELL, R.A.
Apoptosis: death of a monopoly?
SCIENCE 292 865-866 (2001).
2. GERMAIN, M. AND SHORE, G.C.
Cellular distribution of Bcl-2 family proteins.
SCI.STKE 173 PE10 (2003).
3. ADAMS, J.M. AND CORY, S.
The Bcl-2 protein family: arbiters of cell survival.
SCIENCE 281 1322-1326 (1998).
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| Documentation | Apoptosis, or programmed cell death (PCD), is a common and evolutionarily
conserved property of all metazoans [1]. In many biological processes,
apoptosis is required to eliminate supernumerary or dangerous (e.g., pre-
cancerous) cells and to promote normal development. Thus, dysregulation
of apoptosis can contribute to the development of many major diseases,
including cancer, autoimmunity and neurodegenerative disorders. In most
cases, proteins of the caspase family execute the genetic programme that
leads to cell death. Bcl-2 proteins are central regulators of caspase
activation, and play a key role in cell death by regulating the integrity
of the mitochondrial and endoplasmic reticulum (ER) membranes [2]. At
least 20 Bcl-2 proteins have been reported in mammals, and several
others have been identified in viruses.
Bcl-2 family proteins fall roughly into three subtypes, which either promote
cell survival (anti-apoptotic) or trigger cell death (pro-apoptotic). All
members contain at least one of four conserved motifs, termed Bcl-2 Homology
(BH) domains. Bcl-2 subfamily proteins, which contain at least BH1 and BH2,
promote cell survival by inhibiting the adapters needed for the activation
of caspases. Pro-apoptotic members potentially exert their effects by dis-
placing the adapters from the pro-survival proteins; these proteins belong
either to the Bax subfamily, which contain BH1-BH3, or to the BH3 subfamily,
which mostly only feature BH3 [3]. Thus, the balance between antagonistic
family members is believed to play a role in determining cell fate.
Members of the wider Bcl-2 family, which also includes Bcl-x, Bcl-w and
Mcl-1, are described by their similarity to Bcl-2 protein, a member of
the pro-survival Bcl-2 subfamily [3].
BCL2FAMILY is a 3-element fingerprint that provides a signature for the
Bcl-2 apoptosis regulator protein family. The fingerprint was derived
from an initial alignment of 21 sequences: the motifs were drawn from
conserved regions spanning the C-terminal half of the alignment - motif 1
includes the N-terminus of BH1; motif 2 includes the C-terminus of BH1; and
motif 3 includes the N-terminus of BH2. Four iterations on SPTR44_27f were
required to reach convergence, at which point a true set comprising 83
sequences was identified. Numerous partial matches were also found, most of
which appear to be related members of the Bcl-2 family that fail to make
a significant match with motif 1.
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| Sequence Titles | AR11_XENLA Apoptosis regulator R11 (XR11) - Xenopus laevis (African clawed frog).
BAXA_BOVIN Apoptosis regulator BAX, membrane isoform alpha - Bos taurus (Bovine).
BAXA_HUMAN Apoptosis regulator BAX, membrane isoform alpha - Homo sapiens (Human).
BAXA_MOUSE Apoptosis regulator BAX, membrane isoform alpha - Mus musculus (Mouse).
BAXA_RAT Apoptosis regulator BAX, membrane isoform alpha - Rattus norvegicus (Rat).
BAXB_HUMAN Apoptosis regulator BAX, cytoplasmic isoform beta - Homo sapiens (Human).
BAXD_HUMAN BAX protein, cytoplasmic isoform delta - Homo sapiens (Human).
BCL2_BOVIN Apoptosis regulator Bcl-2 - Bos taurus (Bovine).
BCL2_CHICK Apoptosis regulator Bcl-2 - Gallus gallus (Chicken).
BCL2_CRILO Apoptosis regulator Bcl-2 - Cricetulus longicaudatus (Long-tailed hamster) (Chinese hamster).
BCL2_HUMAN Apoptosis regulator Bcl-2 - Homo sapiens (Human).
BCL2_MOUSE Apoptosis regulator Bcl-2 - Mus musculus (Mouse).
BCL2_RAT Apoptosis regulator Bcl-2 - Rattus norvegicus (Rat).
BCLW_HUMAN Apoptosis regulator Bcl-W (BCL2-like 2 protein) - Homo sapiens (Human).
BCLW_MOUSE Apoptosis regulator Bcl-W (BCL2-like 2 protein) - Mus musculus (Mouse).
BCLX_CHICK Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Gallus gallus (Chicken).
BCLX_HUMAN Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Homo sapiens (Human).
BCLX_MOUSE Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Mus musculus (Mouse).
BCLX_PIG Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Sus scrofa (Pig).
BCLX_RAT Apoptosis regulator Bcl-X (BCL2-like 1 protein) - Rattus norvegicus (Rat).
BFL1_HUMAN Bcl-2-related protein A1 (BFL-1 protein) (Hemopoietic-specific early response protein) (GRS protein) - Homo sapiens (Human).
BFL1_MOUSE Bcl-2-related protein A1 (BFL-1 protein) (Hemopoietic-specific early response protein) (A1-A) - Mus musculus (Mouse).
EAR_ASFB7 Apoptosis regulator Bcl-2 homolog precursor - African swine fever virus (strain BA71V) (ASFV).
EAR_ASFE4 Apoptosis regulator Bcl-2 homolog precursor (LMH-5W) - African swine fever virus (strain E-70 / isolate MS44) (ASFV).
EAR_ASFM2 Apoptosis regulator Bcl-2 homolog precursor (LMH-5W) - African swine fever virus (isolate Malawi Lil 20/1) (ASFV).
MCL1_HUMAN Induced myeloid leukemia cell differentiation protein Mcl-1 - Homo sapiens (Human).
O35425 Bcl-2-related ovarian killer protein-like (Apoptosis activator Mtd) - Mus musculus (Mouse).
O35843 Bcl-x-gamma - Mus musculus (Mouse).
O55177 A1-b protein - Mus musculus (Mouse).
O55179 B-cell leukemia/lymphoma 2 related protein A1d - Mus musculus (Mouse).
O88996 Bcl-w - Rattus norvegicus (Rat).
P97287 EAT/MCL-1 PROTEIN (MCL1) (MYELOID CELL LEUKEMIA SEQUENCE 1) - Mus musculus (Mouse).
Q6AYY5 Myeloid cell leukemia sequence 1 - Rattus norvegicus (Rat).
Q6GLI5 Bcl2l1-prov protein - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
Q6GP82 MGC80617 protein - Xenopus laevis (African clawed frog).
Q6NTH7 B-cell leukemia/lymphoma 2 - Mus musculus (Mouse).
Q6P4Y4 Hypothetical protein MGC76049 - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
Q6R755 Bcl-2 - Canis familiaris (Dog).
Q75SV7 Bcl-2 protein - Canis familiaris (Dog).
Q76LT7 Bcl-xL - Canis familiaris (Dog).
Q792S6 Bcl-2-related ovarian killer protein - Rattus norvegicus (Rat).
Q7TS60 BCL-WEL - Rattus norvegicus (Rat).
Q7TS62 Bcl-xbeta - Rattus norvegicus (Rat).
Q7TSN8 Bcl2-like protein - Rattus norvegicus (Rat).
Q7YRZ9 Mcl-1 - Felis silvestris catus (Cat).
Q86W13 A1 splice variant - Homo sapiens (Human).
Q8BEN2 ORF64 - Callitrichine herpesvirus 3.
Q8BQK4 Mus musculus 7 days embryo whole body cDNA, RIKEN full-length enriched library, clone:C430015F12 product:B-cell leukemia/lymphoma 2, full insert sequence - Mus musculus (Mouse).
Q8C5P0 Mus musculus 13 days embryo male testis cDNA, RIKEN full-length enriched library, clone:6030439K11 product:B-cell leukemia/lymphoma 2, full insert sequence - Mus musculus (Mouse).
Q8CFR2 Bcl2l2 protein - Mus musculus (Mouse).
Q8CGL4 Bcl2-like protein 2 - Mus musculus (Mouse).
Q8HYS5 Mcl-1 - Canis familiaris (Dog).
Q8HYU5 Bax - Canis familiaris (Dog).
Q8I008 Bcl-2 protein - Felis silvestris catus (Cat).
Q8K164 B-cell leukemia/lymphoma 2 related protein A1b - Mus musculus (Mouse).
Q8K3J2 Bcl2-associated X protein kappa isoform - Mus musculus (Mouse).
Q8SQ42 Bcl-xl protein - Felis silvestris catus (Cat).
Q8SQ43 Bax-protein - Felis silvestris catus (Cat).
Q8UWD5 Nr13 - Brachydanio rerio (Zebrafish) (Danio rerio).
Q8UWD6 Mcl1b - Brachydanio rerio (Zebrafish) (Danio rerio).
Q8WZ49 Bax isoform psi - Homo sapiens (Human).
Q90Z98 Bcl-XL-like protein 1 - Brachydanio rerio (Zebrafish) (Danio rerio).
Q90ZH2 Bcl-XL - Xenopus laevis (African clawed frog).
Q923R6 B-cell lymphoma protein 2 - Cricetulus longicaudatus (Long-tailed hamster) (Chinese hamster).
Q925A9 BCL2-related protein A1 - Rattus norvegicus (Rat).
Q95KR3 MYELOID CELL LEUKEMIA PROTEIN 1 - Sus scrofa (Pig).
Q967D2 Bcl-x homologous protein, BHP2 - Geodia cydonium (Sponge).
Q98U13 Bax - Xenopus laevis (African clawed frog).
Q9CYW5 Bcl2-like 2 - Mus musculus (Mouse).
Q9DGJ5 Bcl-2-related ovarian killer protein - Gallus gallus (Chicken).
Q9I8I2 Bcl-2-related ovarian killer protein - Gallus gallus (Chicken).
Q9I9N4 Bax (Bcl2-associated X protein) - Brachydanio rerio (Zebrafish) (Danio rerio).
Q9JKL3 Bax protein splice variant k - Rattus norvegicus (Rat).
Q9MYW4 Bcl-X - Oryctolagus cuniculus (Rabbit).
Q9MZS7 Bcl-x long protein - Ovis aries (Sheep).
Q9N1A2 Anti-apoptotic regulator Bcl-xL - Sus scrofa (Pig).
Q9NR76 Bax zeta - Homo sapiens (Human).
Q9NYG7 Bax-sigma - Homo sapiens (Human).
Q9UL32 Bcl-2 related ovarian killer - Homo sapiens (Human).
Q9UMX3 BCL-2-related ovarian killer protein (BOK protein) - Homo sapiens (Human).
Q9UNJ1 MYELOID CELL DIFFERENTIATION PROTEIN (MYELOID CELL LEUKEMIA PROTEIN 1) (MYELOID CELL LEUKEMIA SEQUENCE 1) (BCL2-RELATED) - Homo sapiens (Human).
Q9W6F2 Protein A1 - Gallus gallus (Chicken).
Q9Z1P3 MCL-1 PROTEIN - Rattus norvegicus (Rat).
BCLB_HUMAN Apoptosis regulator Bcl-B (Bcl-2-like 10 protein) (Anti-apoptotic protein NrH) - Homo sapiens (Human).
NR13_COTJA Apoptosis regulator NR-13 - Coturnix coturnix japonica (Japanese quail).
O55178 A1-c protein - Mus musculus (Mouse).
O88857 Bcl-2-related ovarian killer protein - Rattus norvegicus (Rat).
Q677S5 Hypothetical protein - Lymphocystis disease virus - isolate China.
Q6DC66 Zgc:100979 protein - Brachydanio rerio (Zebrafish) (Danio rerio).
Q7KJ42 Pro-apoptotic Bcl-2/Bax-like protein - Drosophila melanogaster (Fruit fly).
Q7KM33 Bcl-2 family member protein - Drosophila melanogaster (Fruit fly).
Q7T381 Similar to BCL2-related ovarian killer - Brachydanio rerio (Zebrafish) (Danio rerio).
Q804D0 Bcl-2 related anti-apoptotic protein - Gallus gallus (Chicken).
Q8T8Y5 AT16536p (CG8238-PA) - Drosophila melanogaster (Fruit fly).
Q90ZN1 Anti-apoptotic NR13 - Gallus gallus (Chicken).
Q99M66 BCL2L10 - Rattus norvegicus (Rat).
Q9DH00 Similar to Apoptosis inhibitor, Bcl2 family proteins (Apoptosis inhibitor-like protein) - Meleagrid herpesvirus 1 (herpesvirus of turkeys).
Q9E1F2 RSORF1 N13-like protein - Meleagrid herpesvirus 1 (herpesvirus of turkeys).
Q9I9N3 MCL-1A (CELL DEATH REGULATOR MCL-1A) - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9N754 BHP1 protein - Suberites domuncula (Sponge).
Q9N9X1 BHP1 protein (BHP1g protein) - Geodia cydonium (Sponge).
Q9UQD6 Bax epsilon - Homo sapiens (Human).
Q9V9C8 Drob-1 (BG1) (Bcl-2 ortholog dBorg-1) (CG33134-PA) (Proapoptotic Bcl-2 homolog DEBCL) - Drosophila melanogaster (Fruit fly).
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