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Protein

Bcl-2-related ovarian killer protein

Gene

Bok

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 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 (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
  • receptor binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

GO - Biological processi

Keywordsi

Biological processApoptosis

Names & Taxonomyi

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

Organism-specific databases

RGDi70984 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

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
  • receptor binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

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
OMAiWADIMKC
OrthoDBiEOG091G0JPB
PhylomeDBiQ792S6
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 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

Similar proteinsi

Entry informationi

Entry nameiBOK_RAT
AccessioniPrimary (citable) accession number: Q792S6
Secondary accession number(s): O88857
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: July 5, 2004
Last modified: March 28, 2018
This is version 103 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health