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Protein

Bcl-2-related ovarian killer protein

Gene

Bok

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Apoptosis regulator that functions through different apoptotic signaling pathways (PubMed:23429263, PubMed:26015568, PubMed:26949185, PubMed:27098698, PubMed:9535847). Plays a roles as pro-apoptotic protein that positively regulates intrinsic apoptotic process in a BAX- and BAK1-dependent manner or in a BAX- and BAK1-independent manner (PubMed:23429263, PubMed:26015568, PubMed:26949185). In response to endoplasmic reticulum stress promotes mitochondrial apoptosis through downstream BAX/BAK1 activation and positive regulation of PERK-mediated unfolded protein response (PubMed:26015568). Activates apoptosis independently of heterodimerization with survival-promoting BCL2 and BCL2L1 through induction of mitochondrial outer membrane permeabilization, in a BAX- and BAK1-independent manner, in response to inhibition of ERAD-proteasome degradation system, resulting in cytochrome c release (PubMed:9535847, PubMed:26949185). In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner. Plays a role in granulosa cell apoptosis by CASP3 activation (By similarity). Plays a roles as anti-apoptotic protein during neuronal apoptotic process, by negatively regulating poly ADP-ribose polymerase-dependent cell death through regulation of neuronal calcium homeostasis and mitochondrial bioenergetics in response to NMDA excitation (PubMed:27098698). In addition to its role in apoptosis, may regulate trophoblast cell proliferation during the early stages of placental development, by acting on G1/S transition through regulation of CCNE1 expression.May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1 (By similarity).By similarity5 Publications

Miscellaneous

'Matador' means killer in Spanish.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Bcl-2-related ovarian killer proteinBy similarity
Alternative name(s):
Apoptosis activator Mtd
Protein matador
Gene namesi
Name:BokImported
Synonyms:Mtd1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1858494 Bok

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei190 – 210HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Knockout Bok mice have a normal development.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25K → R: Increases protein expression and stability; when associated with R-32, R-160 and R-177. Increases apoptosis; when associated with R-32, R-160 and R-177. 1 Publication1
Mutagenesisi32K → R: Increases protein expression and stability; when associated with R-25, R-160 and R-177. Increases apoptosis; when associated with R-25, R-160 and R-177. 1 Publication1
Mutagenesisi34 – 38LGREY → AAAAA: Does not interacts with ITPR1. 1 Publication5
Mutagenesisi34L → G: Does not interacts with ITPR1. Triggers apoptosis. 1 Publication1
Mutagenesisi71L → Q: No change in apoptosis induction; when associated with Q-74 and Q-78. 1 Publication1
Mutagenesisi74L → Q: No change in apoptosis induction; when associated with Q-71 and Q-78. 1 Publication1
Mutagenesisi76D → A: Disrupts homodimerization. Positively regulates intrinsic apoptotic signaling pathway. 1 Publication1
Mutagenesisi78L → Q: No change in apoptosis induction; when associated with Q-71 and Q-74. 1 Publication1
Mutagenesisi160K → R: Increases protein expression and stability; when associated with R-25, R-32 and R-177. Increases apoptosis; when associated with R-25, R-32 and R-177. 1 Publication1
Mutagenesisi177K → R: Increases protein expression and stability; when associated with R-25, R-32 and R-160. Increases apoptosis; when associated with R-25, R-32 and R-160. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430871 – 213Bcl-2-related ovarian killer proteinAdd BLAST213

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7PhosphoserineCombined sources1
Cross-linki25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki160Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated by AMFR/gp78 E3 ubiquitin ligase complex; mediates degradation by ubiquitin-proteasome pathway in a VCP/p97-dependent manner; prevents from proapoptotic activity; promotes degradation of newly synthesized proteins that are not ITPR1 associated.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO35425
PeptideAtlasiO35425
PRIDEiO35425

PTM databases

iPTMnetiO35425
PhosphoSitePlusiO35425

Expressioni

Tissue specificityi

Widely expressed (PubMed:9535847, PubMed:23429263). Highly expressed in brain, kidney, and spleen (PubMed:27098698).3 Publications

Developmental stagei

At E15.0, expressed in brain, liver, thymus, lung, intestinal epithelium and follicles of the whiskers.1 Publication

Inductioni

Induced upon proteasome inhibition.1 Publication

Gene expression databases

BgeeiENSMUSG00000026278 Expressed in 274 organ(s), highest expression level in decidua
CleanExiMM_BOK
ExpressionAtlasiO35425 baseline and differential
GenevisibleiO35425 MM

Interactioni

Subunit structurei

Monomer; positively regulates apoptotic process. Homodimer (PubMed:23429263). Heterodimer (By similarity). Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation (PubMed:26949185). Interacts (via BH4 domain) with ITPR1; enhances BOK expression and stabilization; limits apoptosis and prevents ubiquitination and then degradation; protects ITPR1 from proteolysis by CASP3 during apoptosis (PubMed:27053113, PubMed:23884412). Interacts with ITPR2 AND ITPR3; binds most strongly to ITPR2, and barely to ITPR3; regulates their expression (PubMed:23884412). Interacts with XPO1; translocates to the cytoplasm (By similarity). Interacts with BNIP3; promotes oligomerization (By similarity).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000027499

Structurei

3D structure databases

ProteinModelPortaliO35425
SMRiO35425
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 45Interactions with ITPR11 PublicationAdd BLAST31
Regioni71 – 79Nuclear export signalBy similarity9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 44BH4Add BLAST13
Motifi67 – 83BH3Add BLAST17
Motifi113 – 132BH1Add BLAST20
Motifi165 – 179BH2Add BLAST15

Domaini

BH4 domain mediates interaction with ITPR1.2 Publications

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4728 Eukaryota
ENOG41123S0 LUCA
GeneTreeiENSGT00510000048498
HOGENOMiHOG000290675
HOVERGENiHBG050709
InParanoidiO35425
KOiK02561
OMAiWADIMKC
OrthoDBiEOG091G0JPB
PhylomeDBiO35425
TreeFamiTF315834

Family and domain databases

Gene3Di1.10.437.10, 1 hit
InterProiView protein in InterPro
IPR002475 Bcl2-like
IPR036834 Blc2-like_sf
IPR026298 Blc2_fam
IPR026309 BOK
PANTHERiPTHR11256 PTHR11256, 1 hit
PTHR11256:SF48 PTHR11256:SF48, 1 hit
PfamiView protein in Pfam
PF00452 Bcl-2, 1 hit
PRINTSiPR01862 BCL2FAMILY
SUPFAMiSSF56854 SSF56854, 1 hit
PROSITEiView protein in PROSITE
PS50062 BCL2_FAMILY, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O35425-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MEVLRRSSVF AAEIMDAFDR SPTDKELVAQ AKALGREYVH ARLLRAGLSW
60 70 80 90 100
SAPERASPAP GGRLAEVCTV LLRLGDELEQ IRPSVYRNVA RQLHIPLQSE
110 120 130 140 150
PVVTDAFLAV AGHIFSAGIT WGKVVSLYSV AAGLAVDCVR QAQPAMVHAL
160 170 180 190 200
VDCLGEFVRK TLATWLRRRG GWTDVLKCVV STDPGFRSHW LVATLCSFGR
210
FLKAAFFLLL PER
Length:213
Mass (Da):23,456
Last modified:January 1, 1998 - v1
Checksum:iF8755C45CB05D626
GO
Isoform 2 (identifier: O35425-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Show »
Length:199
Mass (Da):21,866
Checksum:iC107C90A98796082
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WR00A0A087WR00_MOUSE
Bcl-2-related ovarian killer protei...
Bok
121Annotation score:
A0A0J9YUF0A0A0J9YUF0_MOUSE
Bcl-2-related ovarian killer protei...
Bok
132Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0586001 – 14Missing in isoform 2. 1 PublicationAdd BLAST14

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF027707 mRNA Translation: AAC53582.1
BC030069 mRNA Translation: AAH30069.1
CCDSiCCDS15193.1 [O35425-1]
RefSeqiNP_058058.1, NM_016778.3 [O35425-1]
UniGeneiMm.3295

Genome annotation databases

EnsembliENSMUST00000027499; ENSMUSP00000027499; ENSMUSG00000026278 [O35425-1]
ENSMUST00000201863; ENSMUSP00000144347; ENSMUSG00000026278 [O35425-1]
GeneIDi51800
KEGGimmu:51800
UCSCiuc007cee.1 mouse [O35425-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF027707 mRNA Translation: AAC53582.1
BC030069 mRNA Translation: AAH30069.1
CCDSiCCDS15193.1 [O35425-1]
RefSeqiNP_058058.1, NM_016778.3 [O35425-1]
UniGeneiMm.3295

3D structure databases

ProteinModelPortaliO35425
SMRiO35425
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000027499

PTM databases

iPTMnetiO35425
PhosphoSitePlusiO35425

Proteomic databases

PaxDbiO35425
PeptideAtlasiO35425
PRIDEiO35425

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027499; ENSMUSP00000027499; ENSMUSG00000026278 [O35425-1]
ENSMUST00000201863; ENSMUSP00000144347; ENSMUSG00000026278 [O35425-1]
GeneIDi51800
KEGGimmu:51800
UCSCiuc007cee.1 mouse [O35425-1]

Organism-specific databases

CTDi666
MGIiMGI:1858494 Bok

Phylogenomic databases

eggNOGiKOG4728 Eukaryota
ENOG41123S0 LUCA
GeneTreeiENSGT00510000048498
HOGENOMiHOG000290675
HOVERGENiHBG050709
InParanoidiO35425
KOiK02561
OMAiWADIMKC
OrthoDBiEOG091G0JPB
PhylomeDBiO35425
TreeFamiTF315834

Miscellaneous databases

PROiPR:O35425
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026278 Expressed in 274 organ(s), highest expression level in decidua
CleanExiMM_BOK
ExpressionAtlasiO35425 baseline and differential
GenevisibleiO35425 MM

Family and domain databases

Gene3Di1.10.437.10, 1 hit
InterProiView protein in InterPro
IPR002475 Bcl2-like
IPR036834 Blc2-like_sf
IPR026298 Blc2_fam
IPR026309 BOK
PANTHERiPTHR11256 PTHR11256, 1 hit
PTHR11256:SF48 PTHR11256:SF48, 1 hit
PfamiView protein in Pfam
PF00452 Bcl-2, 1 hit
PRINTSiPR01862 BCL2FAMILY
SUPFAMiSSF56854 SSF56854, 1 hit
PROSITEiView protein in PROSITE
PS50062 BCL2_FAMILY, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBOK_MOUSE
AccessioniPrimary (citable) accession number: O35425
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 1, 1998
Last modified: September 12, 2018
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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