Apoptosis Database

Description [+]

Synonyms: BIK, NBK/BLK
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Bcl-2-interacting killer (Apoptosis inducer NBK)(BP4)(BIP1) [Source:UniProtKB/Swiss-Prot;Acc:Q13323]
Family: Bcl-2 family : BH3-only
Process: apoptosis,
Pathways: intrinsic pathway, pre-mitochondrial signaling events,
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Bik
WIKI: BIK-H_sapiens

References [+]

Induction of apoptosis by human Nbk/Bik, a BH3-containing protein that interacts with E1B 19K.
Han J, Sabbatini P, White E
The E1B 19-kilodalton protein (19K protein) is a potent apoptosis inhibitor and the adenovirus homolog of Bcl-2 (E. White, Genes Dev. 10:1-15, 1996). To obtain a better understanding of the biochemical mechanism by which the E1B 19K protein regulates apoptosis, proteins that interact with 19K have been identified; one of these is Bax (J. Han, P. Sabbatini, D. Perez, L. Rao, D. Mohda, and E. White, Genes Dev. 10:461-477, 1996), and another is Bak (S. N. Farrow, J. H. M. White, I. Martinou, T. Raven, K.-T. Pun, C. J. Grinham, J.-C. Martinou, and R. Brown, Nature (London) 374:731-733, 1995). Bax and Bak are Bcl-2 family members which contain Bcl-2 homology regions 1, 2, and 3 (BH1, BH2, and BH3), which interact with E1B 19K and Bcl-2 and promote apoptosis. Like Bax and Bak, Nbk was cloned from a yeast two-hybrid screen for proteins that interact with E1B 19K. Nbk contained BH3 but not BH1 or BH2. It also interacted with Bcl-2 but not with Bax. Both Bcl-2 and E1B 19K interacted with Nbk in vitro, and this interaction was highly specific. In vivo, the Nbk and E1B 19K proteins may colocalize with cytoplasmic and nuclear membranes. Nbk expression functionally antagonized 19K-mediated inhibition of apoptotic cell death and completely prevented transformation by E1A and E1B 19K. Nbk was sufficient for induction of apoptosis in the presence of mutant p53 and thus low levels of Bax, suggesting that Nbk functions independently of Bax to induce apoptosis. Nbk may therefore represent a novel death regulator which contains only a BH3 that interacts with and antagonizes apoptosis inhibitors such as the E1B 19K protein. Mol Cell Biol. 1996 Oct;16(10):5857-64.

BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria.
Germain M, Mathai JP, Shore GC
Stimulation of apoptosis by p53 is accompanied by induction of the BH-3-only proapoptotic member of the BCL-2 family, BIK, and ectopic expression of BIK in p53-null cells caused the release of cytochrome c from mitochondria and activation of caspases, dependent on a functional BH-3 domain. A significant fraction of BIK, which contains a predicted transmembrane segment at its COOH terminus, was found inserted in the endoplasmic reticulum (ER) membrane, with the bulk of the protein facing the cytosol. Restriction of BIK to this membrane by replacing its transmembrane segment with the ER-selective membrane anchor of cytochrome b(5) also retained the cytochrome c release and cell death-inducing activity of BIK. Whereas induction of cell death by BIK was strongly inhibited by the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, the inhibitor was without effect on the ability of BIK to stimulate egress of cytochrome c from mitochondria. This benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone-insensitive pathway for stimulating cytochrome c release from mitochondria by ER BIK was successfully reconstituted in vitro and identified the requirement for components present in the light membrane (ER) and cytosol as necessary for this activity. Collectively, the results identify BIK as an initiator of cytochrome c release from mitochondria operating from a location at the ER. J Biol Chem. 2002 May 17;277(20):18053-60. Epub 2002 Mar 7.

References from Mouse ortholog(s):

Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.
Hegde R, Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES
We identified and cloned a novel murine member of the pro-apoptotic Bcl-2 family. This protein, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane. Blk contains a conserved BH3 domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL. Ectopic expression of Blk in mammalian cells induces apoptosis, which can be inhibited by mutations in the BH3 domain and by overexpression of Bcl-2 or Bcl-xL but not by CrmA. The apoptotic activity of Blk is also inhibited by a dominant negative caspase-9, suggesting that Blk induces apoptosis through activation of the cytochrome c-Apaf-1-caspase-9 pathway. J Biol Chem. 1998 Apr 3;273(14):7783-6.

Proapoptotic BH3-only Bcl-2 family member Bik/Blk/Nbk is expressed in hemopoietic and endothelial cells but is redundant for their programmed death.
Coultas L, Bouillet P, Stanley EG, Brodnicki TC, Adams JM, Strasser A
The BH3-only members of the Bcl-2 protein family are essential for initiation of programmed cell death and stress-induced apoptosis. We have determined the expression pattern in mice of the BH3-only protein Bik, also called Blk or Nbk, and examined its physiological function by gene targeting. We found that Bik is expressed widely in the hematopoietic compartment and in endothelial cells of the venous but not arterial lineages. Nevertheless, its loss did not increase the numbers of such cells in mice or protect hematopoietic cells in vitro from apoptosis induced by cytokine withdrawal or diverse other cytotoxic stimuli. Moreover, whereas loss of the BH3-only protein Bim rescued mice lacking the prosurvival protein Bcl-2 from fatal polycystic kidney disease and lymphopenia, loss of Bik did not. These results indicate that any function of Bik in programmed cell death and stress-induced apoptosis must overlap that of other BH3-only proteins. Mol Cell Biol. 2004 Feb;24(4):1570-81.

Structure & Sequence [+]

Evolution [+]

Name	Relationship	Species
BIK	orthology	Chimpanzee
BIK	orthology	Dog
BIK	orthology	Gorilla
BIK	orthology	Horse
BIK	orthology	Macaca
Bik	orthology	Mouse
BIK	orthology	Orangutan
Bik	orthology	Rat

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0007283	spermatogenesis	biological_proccess	IEA
GO:0042981	regulation of apoptosis	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	TAS
GO:0008584	male gonad development	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	IPI
GO:0005515	protein binding	mollecular_function	IEA
GO:0016020	membrane	cell_component	IEA
GO:0016021	integral to membrane	cell_component	IEA
GO:0005740	mitochondrial envelope	cell_component	IEA

Check GO Evidence Codes here

Curated Isoforms [+]

Transcript	Translation
OTTHUMT00000319676 *	OTTHUMP00000198290 *

Information from other databases [+]

Gene related links:

Gene info from HGNC [?] :1051
Gene related info from GeneCards [?] : BIK
Ensembl genome browser [?] : ENSG00000100290
Expression info from Arrayexpress [?] : ENSG00000100290
Protein expression from Protein Atlas: [?] ENSG00000100290
Community gene edition from Wikigenes: [?] 638

Protein related links:

Uniprot protein info: Q13323
PIR protein info: Q13323
Protein interactions from IntAct: Q13323

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

OMIM gene information: 603392
OMIM disease information:

Other links

entrezgene: 638
refseq_dna: NM_001197
refseq_peptide: NP_001188

Click on [?] for more information.

BIK (Homo sapiens)