Apoptosis Database

Description [+]

Synonyms: BCL2L10, DIVA, BOO, BCL-B
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Apoptosis regulator Bcl-B (Bcl-2-like 10 protein)(Bcl2-L-10)(Anti-apoptotic protein NrH) [Source:UniProtKB/Swiss-Prot;Acc:Q9HD36]
Family: Bcl-2 family Bcl-2 family : multidomain Bcl-2
Process: apoptosis,
Pathways: intrinsic pathway,
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Bcl2l10
WIKI: BCL2L10-H_sapiens

References [+]

Boo, a novel negative regulator of cell death, interacts with Apaf-1.
Song Q, Kuang Y, Dixit VM, Vincenz C
In this report, we describe the cloning and characterization of Boo, a novel anti-apoptotic member of the Bcl-2 family. The expression of Boo was highly restricted to the ovary and epididymis implicating it in the control of ovarian atresia and sperm maturation. Boo contains the conserved BH1 and BH2 domains, but lacks the BH3 motif. Like Bcl-2, Boo possesses a hydrophobic C-terminus and localizes to intracellular membranes. Boo also has an N-terminal region with strong homology to the BH4 domain found to be important for the function of some anti-apoptotic Bcl-2 homologues. Chromosomal localization analysis assigned Boo to murine chromosome 9 at band d9. Boo inhibits apoptosis, homodimerizes or heterodimerizes with some death-promoting and -suppressing Bcl-2 family members. More importantly, Boo interacts with Apaf-1 and forms a multimeric protein complex with Apaf-1 and caspase-9. Bak and Bik, two pro-apoptotic homologues disrupt the association of Boo and Apaf-1. Furthermore, Boo binds to three distinct regions of Apaf-1. These results demonstrate the evolutionarily conserved nature of the mechanisms of apoptosis. Like Ced-9, the mammalian homologues Boo and Bcl-xL interact with the human counterpart of Ced-4, Apaf-1, and thereby regulate apoptosis. EMBO J. 1999 Jan 4;18(1):167-78.

Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death.
Inohara N, Gourley TS, Carrio R, Muniz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Nunez G
We have identified and characterized Diva, which is a novel regulator of apoptosis. Sequence analysis revealed that Diva is a member of the Bcl-2 family of proteins containing Bcl-2 homology domain 1, 2, 3, and 4 (BH1, BH2, BH3, and BH4) regions and a carboxyl-terminal hydrophobic domain. The expression of Diva mRNA was detected in multiple embryonic tissues but was restricted to the ovary and testis in adult mice. The expression of Diva promoted the death of 293T, Ramsey, and T47D cells as well as that of primary sensory neurons, indicating that Diva is a proapoptotic protein. Significantly, Diva lacks critical residues in the conserved BH3 region that mediate the interaction between BH3-containing proapoptotic Bcl-2 homologues and their prosurvival binding partners. Consistent with this, Diva did not bind to cellular Bcl-2 family members including Bcl-2, Bcl-XL, Bcl-w, Mcl-1, and A1/Bfl-1. Furthermore, mutants of Diva lacking the BH3 region fully retained their proapoptotic activity, confirming that Diva promotes apoptosis in a BH3-independent manner. Significantly, Diva interacted with a viral Bcl-2 homologue (vBcl-2) encoded by the Kaposi's sarcoma-associated herpesvirus. Consistent with these associations, apoptosis induced by Diva was inhibited by vBcl-2 but not by Bcl-XL. Importantly, Diva interacted with Apaf-1, an adapter molecule that activates caspase-9, a central death protease of the apoptotic pathway. The expression of Diva inhibited the binding of Bcl-XL to Apaf-1, as determined by immunoprecipitation assays. Thus, Diva represents a novel type of proapoptotic Bcl-2 homologue that promotes apoptosis independently of the BH3 region through direct binding to Apaf-1, thus preventing Bcl-XL from binding to the caspase-9 regulator Apaf-1. J Biol Chem. 1998 Dec 4;273(49):32479-86.

References from Mouse ortholog(s):

Boo, a novel negative regulator of cell death, interacts with Apaf-1.
Song Q, Kuang Y, Dixit VM, Vincenz C
In this report, we describe the cloning and characterization of Boo, a novel anti-apoptotic member of the Bcl-2 family. The expression of Boo was highly restricted to the ovary and epididymis implicating it in the control of ovarian atresia and sperm maturation. Boo contains the conserved BH1 and BH2 domains, but lacks the BH3 motif. Like Bcl-2, Boo possesses a hydrophobic C-terminus and localizes to intracellular membranes. Boo also has an N-terminal region with strong homology to the BH4 domain found to be important for the function of some anti-apoptotic Bcl-2 homologues. Chromosomal localization analysis assigned Boo to murine chromosome 9 at band d9. Boo inhibits apoptosis, homodimerizes or heterodimerizes with some death-promoting and -suppressing Bcl-2 family members. More importantly, Boo interacts with Apaf-1 and forms a multimeric protein complex with Apaf-1 and caspase-9. Bak and Bik, two pro-apoptotic homologues disrupt the association of Boo and Apaf-1. Furthermore, Boo binds to three distinct regions of Apaf-1. These results demonstrate the evolutionarily conserved nature of the mechanisms of apoptosis. Like Ced-9, the mammalian homologues Boo and Bcl-xL interact with the human counterpart of Ced-4, Apaf-1, and thereby regulate apoptosis. EMBO J. 1999 Jan 4;18(1):167-78.

Murine ovarian development is not affected by inactivation of the bcl-2 family member diva.
Russell HR, Lee Y, Miller HL, Zhao J, McKinnon PJ
Diva (also called Boo/Bcl-B) is a member of the Bcl-2 gene family and most likely functions during apoptosis. Diva is highly expressed in the ovary, and both pro- and antiapoptotic functions have been ascribed to this protein. To determine the role of Diva during murine development, we used gene targeting to inactivate DIVA: The Diva-null mice are born at the expected ratios, are fertile, and have no obvious histological abnormalities, and long-term survival did not differ from littermate controls. Additionally, Diva was not required for apoptosis occurring from genotoxic insult in the ovaries or other organs. Thus, Diva is not critical for the normal development of the ovaries, or in its absence its function is subserved by another protein. Mol Cell Biol. 2002 Oct;22(19):6866-70.

Structure & Sequence [+]

Evolution [+]

Name	Relationship	Species
BCL2L10	orthology	Chimpanzee
IPI00824520.1	orthology	Cow
IPI00718256.3	orthology	Cow
MCL1	orthology	Fugu
BCL2L10	orthology	Gorilla
MCL1	orthology	Lyzard
BCL2L10	orthology	Macaca
O_latipes_ENSORLP00000015978	orthology	Medaka
M_domestica_ENSMODP00000002377	orthology	Monodelphis
Bcl2l10	orthology	Mouse
BCL2L10	orthology	Orangutan
BCL2L10	orthology	Rabbit
Bcl2l10	orthology	Rat
D_rerio_ENSDARP00000037180	orthology	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006916	anti-apoptosis	biological_proccess	IDA
GO:0042981	regulation of apoptosis	biological_proccess	IEA
GO:0006919	activation of caspase activity	biological_proccess	TAS
GO:0007283	spermatogenesis	biological_proccess	TAS
GO:0007292	female gamete generation	biological_proccess	TAS
GO:0006915	apoptosis	biological_proccess	IEA
GO:0006916	anti-apoptosis	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0005739	mitochondrion	cell_component	IDA
GO:0005624	membrane fraction	cell_component	TAS
GO:0005829	cytosol	cell_component	IDA
GO:0005634	nucleus	cell_component	IEA
GO:0016020	membrane	cell_component	IEA
GO:0016021	integral to membrane	cell_component	IEA
GO:0031965	nuclear membrane	cell_component	IEA

Check GO Evidence Codes here

Curated Isoforms [+]

Transcript	Translation
OTTHUMT00000254843 *	OTTHUMP00000162719 *

Information from other databases [+]

Gene related links:

Gene info from HGNC [?] :993
Gene related info from GeneCards [?] : BCL2L10
Ensembl genome browser [?] : ENSG00000137875
Expression info from Arrayexpress [?] : ENSG00000137875
Protein expression from Protein Atlas: [?] ENSG00000137875
Community gene edition from Wikigenes: [?] 10017

Protein related links:

Uniprot protein info: Q9HD36
PIR protein info: Q9HD36
Protein interactions from IntAct: Q9HD36

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 606910
OMIM disease information:

Other links

entrezgene: 10017
refseq_dna: NM_020396
refseq_peptide: NP_065129

Click on [?] for more information.

BCL2L10 (Homo sapiens)