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Protein

Bcl-2-related ovarian killer protein

Gene

Bok

Organism
Rattus norvegicus (Rat)
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:9356461, PubMed:9804769). 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 (By similarity). In response to endoplasmic reticulum stress promotes mitochondrial apoptosis through downstream BAX/BAK1 activation and positive regulation of PERK-mediated unfolded protein response (By similarity). 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 (By similarity). In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner. {EXP|h} 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 (By similarity). 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 similarity2 Publications
Isoform 2: positively regulates apoptotic process in an heterodimerization-independent manner with antiapoptotic Bcl-2 proteins.1 Publication

GO - Molecular functioni

  • BH domain binding Source: RGD
  • protein dimerization activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Bcl-2-related ovarian killer protein1 Publication
Gene namesi
Name:BokImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 9

Organism-specific databases

RGDi70984. Bok.

Subcellular locationi

  • Mitochondrion membrane By similarity; Single-pass membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity; Single-pass membrane protein By similarity
  • Mitochondrion inner membrane By similarity
  • Cytoplasm By similarity
  • Nucleus By similarity
  • Mitochondrion By similarity
  • Endoplasmic reticulum By similarity
  • Mitochondrion outer membrane By similarity
  • Early endosome membrane By similarity
  • Recycling endosome membrane By similarity
  • Nucleus outer membrane By similarity
  • Golgi apparatuscis-Golgi network membrane By similarity
  • Golgi apparatustrans-Golgi network membrane By similarity
  • Membrane By similarity

  • Note: Nuclear and cytoplasmic compartments in the early stages of apoptosis and during apoptosis it associates with mitochondria. In healthy cells, associates loosely with the membrane in a hit-and-run mode. The insertion and accumulation on membranes is enhanced through the activity of death signals, resulting in the integration of the membrane-bound protein into the membrane (By similarity). The transmembrane domain controls subcellular localization; constitutes a tail-anchor. Localizes in early and late endosome upon blocking of apoptosis. Must localize to the mitochondria to induce mitochondrial outer membrane permeabilization and apoptosis (By similarity).By similarity

Topology

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71 – 74LLRL → GGGG: Retains proapoptotic activity. Does not heterodimerizes. 1 Publication4
Mutagenesisi75 – 77GDE → AAA: Retains proapoptotic activity. 1 Publication3
Mutagenesisi75G → A: Retains proapoptotic activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430881 – 213Bcl-2-related ovarian killer proteinAdd BLAST213

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7PhosphoserineBy similarity1
Cross-linki25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki160Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

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.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ792S6.
PRIDEiQ792S6.

PTM databases

PhosphoSitePlusiQ792S6.

Expressioni

Tissue specificityi

Expressed in ovary, testis and uterus.1 Publication

Gene expression databases

BgeeiENSRNOG00000018214.
GenevisibleiQ792S6. RN.

Interactioni

Subunit structurei

Isoform 1: Honomer; positively regulates apoptotic process. Homodimer (By similarity). Heterodimer (PubMed:9804769). Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation. 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. Interacts with ITPR2 AND ITPR3; binds most strongly to ITPR2, and barely to ITPR3; regulates their expression (By similarity). Interacts with XPO1; translocates to the cytoplasm. Interacts with BNIP3; promotes oligomerization (By similarity). Isoform 2: Does not heterodimerize with antiapoptotic Bcl-2 proteins (PubMed:9804769).By similarity1 Publication

GO - Molecular functioni

  • BH domain binding Source: RGD
  • protein dimerization activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024693.

Structurei

3D structure databases

ProteinModelPortaliQ792S6.
SMRiQ792S6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 45Interactions with ITPR1By similarityAdd 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.By similarity

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00510000048498.
HOGENOMiHOG000290675.
HOVERGENiHBG050709.
InParanoidiQ792S6.
KOiK02561.
OMAiCRDYIHS.
OrthoDBiEOG091G0JPB.
PhylomeDBiQ792S6.
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 splicing. AlignAdd to basket

Isoform 1 (identifier: Q792S6-1) [UniParc]FASTAAdd to basket
Also known as: Bok-L1 Publication

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:July 5, 2004 - v1
Checksum:iF8755C45CB05D626
GO
Isoform 2 (identifier: Q792S6-2) [UniParc]FASTAAdd to basket
Also known as: Bok-S1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     75-117: Missing.

Show »
Length:170
Mass (Da):18,729
Checksum:i15E54361F448CF16
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01244775 – 117Missing in isoform 2. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF027954 mRNA. Translation: AAB87418.1.
AF051093 mRNA. Translation: AAC61928.1.
BC078871 mRNA. Translation: AAH78871.1.
RefSeqiNP_059008.1. NM_017312.2. [Q792S6-1]
XP_017451805.1. XM_017596316.1. [Q792S6-1]
UniGeneiRn.44461.

Genome annotation databases

EnsembliENSRNOT00000024526; ENSRNOP00000024526; ENSRNOG00000018214. [Q792S6-2]
ENSRNOT00000024695; ENSRNOP00000024693; ENSRNOG00000018214. [Q792S6-1]
GeneIDi29884.
KEGGirno:29884.
UCSCiRGD:70984. rat. [Q792S6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF027954 mRNA. Translation: AAB87418.1.
AF051093 mRNA. Translation: AAC61928.1.
BC078871 mRNA. Translation: AAH78871.1.
RefSeqiNP_059008.1. NM_017312.2. [Q792S6-1]
XP_017451805.1. XM_017596316.1. [Q792S6-1]
UniGeneiRn.44461.

3D structure databases

ProteinModelPortaliQ792S6.
SMRiQ792S6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024693.

PTM databases

PhosphoSitePlusiQ792S6.

Proteomic databases

PaxDbiQ792S6.
PRIDEiQ792S6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000024526; ENSRNOP00000024526; ENSRNOG00000018214. [Q792S6-2]
ENSRNOT00000024695; ENSRNOP00000024693; ENSRNOG00000018214. [Q792S6-1]
GeneIDi29884.
KEGGirno:29884.
UCSCiRGD:70984. rat. [Q792S6-1]

Organism-specific databases

CTDi666.
RGDi70984. Bok.

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00510000048498.
HOGENOMiHOG000290675.
HOVERGENiHBG050709.
InParanoidiQ792S6.
KOiK02561.
OMAiCRDYIHS.
OrthoDBiEOG091G0JPB.
PhylomeDBiQ792S6.
TreeFamiTF315834.

Miscellaneous databases

PROiQ792S6.

Gene expression databases

BgeeiENSRNOG00000018214.
GenevisibleiQ792S6. RN.

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_RAT
AccessioniPrimary (citable) accession number: Q792S6
Secondary accession number(s): O88857
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 93 of the entry and version 1 of the sequence. [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

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.