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BOK (BCL2-related ovarian killer)

Written2006-11Alexander G Yakovlev
Department of Neuroscience, Research Building, Room WP14, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesMtd (Matador)
BOKL
BCL2-like 9
BCL2L9
MGC4631
HGNC (Hugo) BOK
LocusID (NCBI) 666
Atlas_Id 824
Location 2q37.3  [Link to chromosome band 2q37]
Location_base_pair Starts at 242498146 and ends at 242513553 bp from pter ( according to hg19-Feb_2009)  [Mapping BOK.png]
Local_order LOC728248 STK25 BOK THAP4 ATG4B
Fusion genes
(updated 2016)
BOK (2q37.3) / MYEOV2 (2q37.3)BOK (2q37.3) / SNRPB (20p13)PASK (2q37.3) / BOK (2q37.3)

DNA/RNA

Description The gene encompasses 15,361 bp of DNA with 5 exons.
Transcription Alternative splicing results in expression of two mRNA variants. The full-length (Bok-L) mRNA comprises 2.6 kb with the 639 bp open reading frame. The truncated form (Bok-S) results from skipping of exon three and a deletion of 43 bp in the Bok-L coding region. It has been shown that transcription activity of the Bok gene depends on expression of p53 and can be directly regulated at the gene promoter level by E2F transcription factors during cell cycle progression.

Protein

Description A Bok transcript was initially isolated from a rat ovarian fusion cDNA library. Sequencing of this transcript has revealed that full-length BOK protein consists of 213 amino acids and contains three conserved BCL2 homology regions BH1, BH2, and BH3 in addition to a C-terminal transmembrane domain. BOK-S that results from the alternative splicing has its N-terminal BH3 domain part fused to the C-terminal part of the BH1 region. Using the yeast two-hybrid system, it has been demonstrated that, although the BH domains composition of BOK-L protein was similar to that of BAX and BAK, it interacted only with MCL-1, BHRF1, and BCL2A1/BFL-1 but not other anti-apoptotic multidomain BCL-2 family members.
Expression Bok mRNA was isolated from the ovarian cDNA library. Results of Northern blot analysis revealed high expression levels of Bok mRNA in the reproductive tissues, such as ovary, testis, and uterus. Using in situ hybridization the authors localized Bok mRNA in granulosa cells. However, Bok expression is also evident in other mammalian tissues, such as brain, liver, thymus, lung, heart, kidney intestinal epithelium and lymphoid tissues.
Localisation Intracellular localization of BOK protein remains to be clarified. Results of different studies suggest either its mitochondrial or cytosolic and nuclear localization.
Function BOK promotes both caspase-dependent and caspase-independent apoptosis at the level of mitochondria in various cell types by promoting the release of pro-apoptotic mitochondrial factors to the cell cytosol. Inhibition of BOK induction using siRNA markedly decreases p53-dependent cell death. However, a specific mechanism, by which BOK increases mitochondrial membrane permeability, remains unknown. Apoptosis induced by BOK overexpression cannot be inhibited by Bcl-2 or Bcl-XL suggesting a unique role for BOK in apoptosis. A recent report indicates that BOK may cooperate with a BH3-only member, NOXA in p53-dependent apoptosis induced by DNA damage in human neuroblastoma cells, where it substitutes for a function of pro-apoptotic BAX.
Homology Evolutionary conserved from fly to human.

Mutations

Note Unknown.

Bibliography

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
Molecular carcinogenesis. 2006 ; 45 (2) : 73-83.
PMID 16302269
 
Role of Mtd/Bok in normal and neoplastic B-cell development in the bursa of Fabricius.
Brown CY, Bowers SJ, Loring G, Heberden C, Lee RM, Neiman PE
Developmental and comparative immunology. 2004 ; 28 (6) : 619-634.
PMID 15177115
 
Loss of proapoptotic Bcl-2-related multidomain proteins in primary melanomas is associated with poor prognosis.
Fecker LF, Geilen CC, Tchernev G, Trefzer U, Assaf C, Kurbanov BM, Schwarz C, Daniel PT, Eberle J
The Journal of investigative dermatology. 2006 ; 126 (6) : 1366-1371.
PMID 16528364
 
Membrane translocation and oligomerization of hBok are triggered in response to apoptotic stimuli and Bnip3.
Gao S, Fu W, Dürrenberger M, De Geyter C, Zhang H
Cellular and molecular life sciences : CMLS. 2005 ; 62 (9) : 1015-1024.
PMID 15868100
 
The expression of Bok is regulated by serum in HC11 mammary epithelial cells.
Ha SH, Lee SR, Lee TH, Kim YM, Baik MG, Choi YJ
Molecules and cells. 2001 ; 12 (3) : 368-371.
PMID 11804337
 
A splicing variant of the Bcl-2 member Bok with a truncated BH3 domain induces apoptosis but does not dimerize with antiapoptotic Bcl-2 proteins in vitro.
Hsu SY, Hsueh AJ
The Journal of biological chemistry. 1998 ; 273 (46) : 30139-30146.
PMID 9804769
 
Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members.
Hsu SY, Kaipia A, McGee E, Lomeli M, Hsueh AJ
Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (23) : 12401-12406.
PMID 9356461
 
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, Nez G
The Journal of biological chemistry. 1998 ; 273 (15) : 8705-8710.
PMID 9535847
 
Bcl-2-related protein family gene expression during oligodendroglial differentiation.
Itoh T, Itoh A, Pleasure D
Journal of neurochemistry. 2003 ; 85 (6) : 1500-1512.
PMID 12787069
 
Bok, Bcl-2-related Ovarian Killer, Is Cell Cycle-regulated and Sensitizes to Stress-induced Apoptosis.
Rodriguez JM, Glozak MA, Ma Y, Cress WD
The Journal of biological chemistry. 2006 ; 281 (32) : 22729-22735.
PMID 16772296
 
BOK and NOXA are essential mediators of p53-dependent apoptosis.
Yakovlev AG, Di Giovanni S, Wang G, Liu W, Stoica B, Faden AI
The Journal of biological chemistry. 2004 ; 279 (27) : 28367-28374.
PMID 15102863
 
Evolutionarily conserved Bok proteins in the Bcl-2 family.
Zhang H, Holzgreve W, De Geyter C
FEBS letters. 2000 ; 480 (2-3) : 311-313.
PMID 11034351
 

Citation

This paper should be referenced as such :
Yakovlev, AG
BOK (Bcl2-related ovarian killer)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):86-87.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BOKID824ch2q37.html


External links

Nomenclature
HGNC (Hugo)BOK   1087
Cards
AtlasBOKID824ch2q37
Entrez_Gene (NCBI)BOK  666  BCL2-related ovarian killer
AliasesBCL2L9; BOKL
GeneCards (Weizmann)BOK
Ensembl hg19 (Hinxton)ENSG00000176720 [Gene_View]  chr2:242498146-242513553 [Contig_View]  BOK [Vega]
Ensembl hg38 (Hinxton)ENSG00000176720 [Gene_View]  chr2:242498146-242513553 [Contig_View]  BOK [Vega]
ICGC DataPortalENSG00000176720
TCGA cBioPortalBOK
AceView (NCBI)BOK
Genatlas (Paris)BOK
WikiGenes666
SOURCE (Princeton)BOK
Genomic and cartography
GoldenPath hg19 (UCSC)BOK  -     chr2:242498146-242513553 +  2q37.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)BOK  -     2q37.3   [Description]    (hg38-Dec_2013)
EnsemblBOK - 2q37.3 [CytoView hg19]  BOK - 2q37.3 [CytoView hg38]
Mapping of homologs : NCBIBOK [Mapview hg19]  BOK [Mapview hg38]
OMIM605404   
Gene and transcription
Genbank (Entrez)AF174487 BC006203 BC017214 BG118500 BI550157
RefSeq transcript (Entrez)NM_032515
RefSeq genomic (Entrez)NC_000002 NC_018913 NG_029488 NT_005403 NW_004929308
Consensus coding sequences : CCDS (NCBI)BOK
Cluster EST : UnigeneHs.734656 [ NCBI ]
CGAP (NCI)Hs.734656
Alternative Splicing GalleryENSG00000176720
Gene ExpressionBOK [ NCBI-GEO ]   BOK [ EBI - ARRAY_EXPRESS ]   BOK [ SEEK ]   BOK [ MEM ]
Gene Expression Viewer (FireBrowse)BOK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)666
GTEX Portal (Tissue expression)BOK
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UMX3 (Uniprot)
NextProtQ9UMX3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UMX3
Splice isoforms : SwissVarQ9UMX3 (Swissvar)
PhosPhoSitePlusQ9UMX3
Domaine pattern : Prosite (Expaxy)BCL2_FAMILY (PS50062)   
Domains : Interpro (EBI)Bcl2-like    Blc2_fam    BOK   
Domain families : Pfam (Sanger)Bcl-2 (PF00452)   
Domain families : Pfam (NCBI)pfam00452   
DMDM Disease mutations666
Blocks (Seattle)BOK
SuperfamilyQ9UMX3
Human Protein AtlasENSG00000176720
Peptide AtlasQ9UMX3
HPRD05657
IPIIPI00000133   IPI00003307   
Protein Interaction databases
DIP (DOE-UCLA)Q9UMX3
IntAct (EBI)Q9UMX3
FunCoupENSG00000176720
BioGRIDBOK
STRING (EMBL)BOK
ZODIACBOK
Ontologies - Pathways
QuickGOQ9UMX3
Ontology : AmiGOGolgi membrane  protein binding  nucleus  cytoplasm  mitochondrion  mitochondrial outer membrane  endoplasmic reticulum membrane  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  brain development  cell proliferation  male gonad development  intrinsic apoptotic signaling pathway in response to DNA damage  integral component of membrane  mitochondrial membrane  protein homodimerization activity  protein heterodimerization activity  oligodendrocyte differentiation  BH domain binding  neuron apoptotic process  intrinsic apoptotic signaling pathway by p53 class mediator  extrinsic apoptotic signaling pathway in absence of ligand  positive regulation of execution phase of apoptosis  
Ontology : EGO-EBIGolgi membrane  protein binding  nucleus  cytoplasm  mitochondrion  mitochondrial outer membrane  endoplasmic reticulum membrane  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  brain development  cell proliferation  male gonad development  intrinsic apoptotic signaling pathway in response to DNA damage  integral component of membrane  mitochondrial membrane  protein homodimerization activity  protein heterodimerization activity  oligodendrocyte differentiation  BH domain binding  neuron apoptotic process  intrinsic apoptotic signaling pathway by p53 class mediator  extrinsic apoptotic signaling pathway in absence of ligand  positive regulation of execution phase of apoptosis  
NDEx NetworkBOK
Atlas of Cancer Signalling NetworkBOK
Wikipedia pathwaysBOK
Orthology - Evolution
OrthoDB666
GeneTree (enSembl)ENSG00000176720
Phylogenetic Trees/Animal Genes : TreeFamBOK
Homologs : HomoloGeneBOK
Homology/Alignments : Family Browser (UCSC)BOK
Gene fusions - Rearrangements
Fusion : MitelmanBOK/MYEOV2 [2q37.3/2q37.3]  
Fusion : MitelmanPASK/BOK [2q37.3/2q37.3]  [t(2;2)(q37;q37)]  
Fusion: TCGABOK 2q37.3 MYEOV2 2q37.3 BRCA
Fusion: TCGAPASK 2q37.3 BOK 2q37.3 LUAD
Polymorphisms : SNP, variants
NCBI Variation ViewerBOK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BOK
dbVarBOK
ClinVarBOK
1000_GenomesBOK 
Exome Variant ServerBOK
ExAC (Exome Aggregation Consortium)BOK (select the gene name)
Genetic variants : HAPMAP666
Genomic Variants (DGV)BOK [DGVbeta]
Mutations
ICGC Data PortalBOK 
TCGA Data PortalBOK 
Broad Tumor PortalBOK
OASIS PortalBOK [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBOK 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BOK
DgiDB (Drug Gene Interaction Database)BOK
DoCM (Curated mutations)BOK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BOK (select a term)
intoGenBOK
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)2:242498146-242513553  ENSG00000176720
CONAN: Copy Number AnalysisBOK 
Mutations and Diseases : HGMDBOK
OMIM605404   
MedgenBOK
Genetic Testing Registry BOK
NextProtQ9UMX3 [Medical]
TSGene666
GENETestsBOK
Huge Navigator BOK [HugePedia]
snp3D : Map Gene to Disease666
BioCentury BCIQBOK
ClinGenBOK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD666
Chemical/Pharm GKB GenePA25396
Clinical trialBOK
Miscellaneous
canSAR (ICR)BOK (select the gene name)
Probes
Litterature
PubMed26 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBOK
EVEXBOK
GoPubMedBOK
iHOPBOK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Sep 19 19:25:56 CEST 2016

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