Apoptosis Database

Description [+]

Synonyms: BOKA, BCL2-RELATED OVARIAN KILLER A, BOK, ZBOK1, ZGC:100979
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
Short gene description: Bcl-2-related ovarian killer protein homolog A (zBok1). [Source:UniProtKB/Swiss-Prot;Acc:Q6DC66]
Family: Bcl-2 family : multidomain Bcl-2
Process: undefined,
Pathways: intrinsic pathway,
Criteria: manually curated
Curator comment:
Human ortholog(s): BOK
WIKI: BOKA-D_rerio

References [+]

Functional characterization of the Bcl-2 gene family in the zebrafish.
Kratz E, Eimon PM, Mukhyala K, Stern H, Zha J, Strasser A, Hart R, Ashkenazi A
Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway. Cell Death Differ. 2006 Oct;13(10):1631-40. Epub 2006 Aug 4.

References from Human ortholog(s):

Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induces apoptosis.
Bartholomeusz G, Wu Y, Ali Seyed M, Xia W, Kwong KY, Hortobagyi G, Hung MC
The anti-apoptotic members of the Bcl-2 family, such as Bcl-2 and Bcl-XL, play a central role in preventing the induction of apoptosis via the intrinsic apoptotic pathway. It has been previously shown that induction of apoptosis by the pro-apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-xL, suggesting that Bok might have a unique role in the apoptotic cascade. We showed here that human Bok is the only member of the Bcl-2 family to have a leucine-rich sequence indicative of a nuclear export signal within its BH3 domain. Western blot analysis of nuclear and cytoplasmic fractions identified Bok in both the nucleus and the cytoplasm of HEK 293T cells, HeLa cells, and breast cancer cells, and its nuclear concentration increased after treatment of those cells with leptomycin B, an inhibitor of the exportin Crm1. Immunocytochemistry of flag-tagged Bok confirmed its nuclear localization. Mutating the nuclear export signal of Bok by site-directed mutagenesis resulted in an increase in its nuclear localization and apoptotic activity. We also found that Crm1 interacted with wild-type Bok but not with the mutated form. These results suggest that nuclear export of Bok is a regulated process mediated by Crm1, and constitutes the first report of a link between the apoptotic activity and nuclear localization of a pro-apoptotic member of the Bcl-2 family. Mol Carcinog. 2006 Feb;45(2):73-83.

Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.
Inohara N, Ekhterae D, Garcia I, Carrio R, Merino J, Merry A, Chen S, Nunez G
We have identified and characterized Mtd, a novel regulator of apoptosis. Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted the death of primary sensory neurons, 293T cells and HeLa cells, indicating that Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2 family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2 or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids in the BH3 domain retained its ability to promote apoptosis, further indicating that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd-induced apoptosis was not blocked by broad range synthetic caspase inhibitors z-VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally occurring Bcl-2 family member that can activate apoptosis independently of heterodimerization with survival-promoting Bcl-2 and Bcl-XL. J Biol Chem. 1998 Apr 10;273(15):8705-10.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Bcl-2	68	180

Evolution [+]

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Homologs list [+]

Name	Relationship	Species
A_aegypti_AAEL001521-PA	orthology	Aedes
A_aegypti_AAEL001515-PA	orthology	Aedes
Q2PHG8_ANOGA	orthology	Anopheles
BOK_CHICK	orthology	Chicken
C_intestinalis_ENSCINP00000016140	orthology	Ciona
NP_001092338.1	orthology	Cow
debcl	orthology	Fly
Buffy	orthology	Fly
BOK (1 of 2)	orthology	Fugu
BOK (1 of 2)	orthology	Gasterosteus
BOK	orthology	Gorilla
BOK	orthology	Horse
BOK	orthology	Human
BOK	orthology	Lyzard
BOK	orthology	Macaca
BOK (1 of 2)	orthology	Medaka
BOK	orthology	Monodelphis
Bok	orthology	Mouse
BOK	orthology	Orangutan
BOK	orthology	Ornithorhynchus
Bok	orthology	Rat
BOK (1 of 2)	orthology	Tetraodon
BOK	orthology	Zebra finch
BCL2_CHICK	paralogy	Chicken
BCLX_CHICK	paralogy	Chicken
BCL2L1	paralogy	Chimpanzee
BCL2L2	paralogy	Chimpanzee
BAX	paralogy	Chimpanzee
C_intestinalis_ENSCINP00000019812	paralogy	Ciona
BCLW_BOVIN	paralogy	Cow
BAX_BOVIN	paralogy	Cow
NP_001070954.1	paralogy	Cow
NP_001003072.1	paralogy	Dog
BCL2	paralogy	Fugu
BOK (2 of 2)	paralogy	Fugu
BAX	paralogy	Fugu
BCL2L1 (2 of 6)	paralogy	Fugu
BCL2L1 (1 of 6)	paralogy	Fugu
BOK (2 of 2)	paralogy	Gasterosteus
BCL2L1 (2 of 2)	paralogy	Gasterosteus
G_aculeatus_ENSGACP00000018978	paralogy	Gasterosteus
BAX	paralogy	Gasterosteus
BCL2	paralogy	Gasterosteus
BCL2L1 (1 of 2)	paralogy	Gasterosteus
BCL2L2	paralogy	Gorilla
BCL2L2	paralogy	Horse
BCL2L1	paralogy	Horse
BCL2L1	paralogy	Human
BAX	paralogy	Human
BCL2L2	paralogy	Human
BAK1	paralogy	Lyzard
BCL2L1	paralogy	Lyzard
BCL2	paralogy	Lyzard
BCL2L2	paralogy	Macaca
BAX	paralogy	Macaca
BCL2L1	paralogy	Macaca
BOK (2 of 2)	paralogy	Medaka
BCL2L1	paralogy	Medaka
BCL2	paralogy	Medaka
BCL2L1	paralogy	Monodelphis
BCL2A1	paralogy	Monodelphis
M_domestica_ENSMODP00000005598	paralogy	Monodelphis
BAX	paralogy	Monodelphis
Bcl2l2	paralogy	Mouse
Bcl2l1	paralogy	Mouse
Bax	paralogy	Mouse
BCL2L1	paralogy	Orangutan
BCL2L2	paralogy	Ornithorhynchus
BAX	paralogy	Rabbit
Q9MYW4_RABIT	paralogy	Rabbit
BCLX_RAT	paralogy	Rat
Bax	paralogy	Rat
BOK (2 of 2)	paralogy	Tetraodon
BCL2L1 (2 of 3)	paralogy	Tetraodon
BCL2L1 (1 of 3)	paralogy	Tetraodon
BCL2	paralogy	Tetraodon
T_nigroviridis_ENSTNIP00000017211	paralogy	Tetraodon
BCL2	paralogy	Xenopus
BCL2L1	paralogy	Xenopus
bax	paralogy	Xenopus
bcl2l2	paralogy	Xenopus
BCL2L1	paralogy	Zebra finch
BCL2	paralogy	Zebra finch
bcl2	paralogy	Zebrafish
zgc:153993	paralogy	Zebrafish
bcl2l	paralogy	Zebrafish
baxa	paralogy	Zebrafish
bokb	paralogy	Zebrafish

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Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0042981	regulation of apoptosis	biological_proccess	IEA
GO:0006915	apoptosis	biological_proccess	IEA

Information from other databases [+]

BOKA (Danio rerio)