Bcl-2-interacting killer

BCL2-interacting killer (apoptosis-inducing)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2IPE​
Identifiers
Symbols	BIK ; BIP1; BP4; NBK
External IDs	OMIM: 603392 MGI: 1206591 HomoloGene: 924 GeneCards: BIK Gene
Gene ontology Molecular function • protein binding • protein heterodimerization activity • BH domain binding Cellular component • endomembrane system • integral component of membrane • mitochondrial membrane Biological process • apoptotic process • spermatogenesis • male gonad development • apoptotic mitochondrial changes • positive regulation of protein homooligomerization • positive regulation of release of cytochrome c from mitochondria Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	638	12124
Ensembl	ENSG00000100290	ENSMUSG00000016758
UniProt	Q13323	O70337
RefSeq (mRNA)	NM_001197	NM_007546
RefSeq (protein)	NP_001188	NP_031572
Location (UCSC)	Chr 22: 43.11 – 43.13 Mb	Chr 15: 83.53 – 83.54 Mb
PubMed search

Bcl-2-interacting killer is a protein that in humans is encoded by the BIK gene.^[1][2][3]

Function

The protein encoded by this gene is known to interact with cellular and viral survival-promoting proteins, such as BCL2 and the Epstein-Barr virus in order to enhance programmed cell death. Because its activity is suppressed in the presence of survival-promoting proteins, this protein is suggested as a likely target for antiapoptotic proteins. This protein shares a critical BH3 domain with other death-promoting proteins, BAX and BAK.^[3]

Interactions

Bcl-2-interacting killer has been shown to interact with BCL2-like 1^[4][5][6][7] and Bcl-2.^[5][6]

References

1. Boyd JM, Gallo GJ, Elangovan B, Houghton AB, Malstrom S, Avery BJ, Ebb RG, Subramanian T, Chittenden T, Lutz RJ (Dec 1995). "Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins". Oncogene 11 (9): 1921–8. PMID 7478623.
2. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
3. "Entrez Gene: BIK BCL2-interacting killer (apoptosis-inducing)".
4. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
5. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
6. Gillissen B, Essmann F, Graupner V, Stärck L, Radetzki S, Dörken B, Schulze-Osthoff K, Daniel PT (July 2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". EMBO J. 22 (14): 3580–90. doi:10.1093/emboj/cdg343. PMC 165613. PMID 12853473.
7. Jiang A, Clark EA (May 2001). "Involvement of Bik, a proapoptotic member of the Bcl-2 family, in surface IgM-mediated B cell apoptosis". J. Immunol. 166 (10): 6025–33. doi:10.4049/jimmunol.166.10.6025. PMID 11342619.

Further reading

• Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ (1996). "A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.". EMBO J. 14 (22): 5589–96. PMC 394673. PMID 8521816.
• Han J, Sabbatini P, White E (1996). "Induction of apoptosis by human Nbk/Bik, a BH3-containing protein that interacts with E1B 19K.". Mol. Cell. Biol. 16 (10): 5857–64. PMC 231587. PMID 8816500.
• Inohara N, Ding L, Chen S, Núñez G (1997). "harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L).". EMBO J. 16 (7): 1686–94. doi:10.1093/emboj/16.7.1686. PMC 1169772. PMID 9130713.
• Huang DC, Adams JM, Cory S (1998). "The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4.". EMBO J. 17 (4): 1029–39. doi:10.1093/emboj/17.4.1029. PMC 1170452. PMID 9463381.
• Hegde R, Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES (1998). "Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a potent death agonist.". J. Biol. Chem. 273 (14): 7783–6. doi:10.1074/jbc.273.14.7783. PMID 9525867.
• Ohi N, Tokunaga A, Tsunoda H, Nakano K, Haraguchi K, Oda K, Motoyama N, Nakajima T (1999). "A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region.". Cell Death Differ. 6 (4): 314–25. doi:10.1038/sj.cdd.4400493. PMID 10381623.
• Holmgreen SP, Huang DC, Adams JM, Cory S (1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members.". Cell Death Differ. 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. PMID 10381646.
• Castells A, Ino Y, Louis DN, Ramesh V, Gusella JF, Rustgi AK (1999). "Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer.". Gastroenterology 117 (4): 831–7. doi:10.1016/S0016-5085(99)70341-0. PMID 10500065.
• Verma S, Budarf ML, Emanuel BS, Chinnadurai G (2000). "Structural analysis of the human pro-apoptotic gene Bik: chromosomal localization, genomic organization and localization of promoter sequences.". Gene 254 (1–2): 157–62. doi:10.1016/S0378-1119(00)00276-6. PMID 10974546.
• Jiang A, Clark EA (2001). "Involvement of Bik, a proapoptotic member of the Bcl-2 family, in surface IgM-mediated B cell apoptosis". J. Immunol. 166 (10): 6025–33. doi:10.4049/jimmunol.166.10.6025. PMID 11342619.
• Federici M, Hribal M, Perego L, Ranalli M, Caradonna Z, Perego C, Usellini L, Nano R, Bonini P, Bertuzzi F, Marlier LN, Davalli AM, Carandente O, Pontiroli AE, Melino G, Marchetti P, Lauro R, Sesti G, Folli F (2001). "High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program". Diabetes 50 (6): 1290–301. doi:10.2337/diabetes.50.6.1290. PMID 11375329.
• Zou Y, Peng H, Zhou B, Wen Y, Wang SC, Tsai EM, Hung MC (2002). "Systemic tumor suppression by the proapoptotic gene bik". Cancer Res. 62 (1): 8–12. PMID 11782349.
• Germain M, Mathai JP, Shore GC (2002). "BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria". J. Biol. Chem. 277 (20): 18053–60. doi:10.1074/jbc.M201235200. PMID 11884414.
• Gillissen B, Essmann F, Graupner V, Stärck L, Radetzki S, Dörken B, Schulze-Osthoff K, Daniel PT (2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". EMBO J. 22 (14): 3580–90. doi:10.1093/emboj/cdg343. PMC 165613. PMID 12853473.
• Arena V, Martini M, Luongo M, Capelli A, Larocca LM (2003). "Mutations of the BIK gene in human peripheral B-cell lymphomas". Genes Chromosomes Cancer 38 (1): 91–6. doi:10.1002/gcc.10245. PMID 12874789.
• Hur J, Chesnes J, Coser KR, Lee RS, Geck P, Isselbacher KJ, Shioda T (2004). "The Bik BH3-only protein is induced in estrogen-starved and antiestrogen-exposed breast cancer cells and provokes apoptosis". Proc. Natl. Acad. Sci. U.S.A. 101 (8): 2351–6. doi:10.1073/pnas.0307337101. PMC 356954. PMID 14983013.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.