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Protein

Bcl-2-related ovarian killer protein

Gene

Bok

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 apototic 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

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1858494. Bok.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • cis-Golgi network membrane Source: UniProtKB
  • cytoplasm Source: MGI
  • early endosome membrane Source: UniProtKB
  • endoplasmic reticulum Source: MGI
  • endoplasmic reticulum membrane Source: UniProtKB
  • Golgi apparatus Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial inner membrane Source: MGI
  • mitochondrial membrane Source: UniProtKB
  • mitochondrial outer membrane Source: GO_Central
  • mitochondrion Source: MGI
  • nuclear outer membrane Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB
  • trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

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.
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 heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

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.
OMAiCRDYIHS.
OrthoDBiEOG091G0JPB.
PhylomeDBiO35425.
TreeFamiTF315834.

Family and domain databases

InterProiIPR002475. Bcl2-like.
IPR026298. Blc2_fam.
IPR026309. BOK.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF48. PTHR11256:SF48. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
[Graphical view]
PRINTSiPR01862. BCL2FAMILY.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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.
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

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.
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.
OMAiCRDYIHS.
OrthoDBiEOG091G0JPB.
PhylomeDBiO35425.
TreeFamiTF315834.

Miscellaneous databases

PROiO35425.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026278.
CleanExiMM_BOK.
ExpressionAtlasiO35425. baseline and differential.
GenevisibleiO35425. MM.

Family and domain databases

InterProiIPR002475. Bcl2-like.
IPR026298. Blc2_fam.
IPR026309. BOK.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF48. PTHR11256:SF48. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
[Graphical view]
PRINTSiPR01862. BCL2FAMILY.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBOK_MOUSE
AccessioniPrimary (citable) accession number: O35425
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

'Matador' means killer in Spanish.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.