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Protein

Bcl-2-related ovarian killer protein

Gene

BOK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 1: Apoptosis regulator that functions through different apoptotic signaling pathways (PubMed:27076518, PubMed:15102863, PubMed:20673843). 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:27076518, PubMed:15102863). 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 (PubMed:27076518). In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner (PubMed:15102863). Plays a role in granulosa cell apoptosis by CASP3 activation (PubMed:20673843). 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 (PubMed:19942931). May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1 (PubMed:24113155).By similarity5 Publications
Isoform 2: Pro-apoptotic molecule exerting its function through the mitochondrial pathway.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Bcl-2-related ovarian killer protein1 Publication
Short name:
hBOK1 Publication
Alternative name(s):
Bcl-2-like protein 9
Short name:
Bcl2-L-9
Gene namesi
Name:BOKImported
Synonyms:BCL2L9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000176720.4.
HGNCiHGNC:1087. 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
Transmembranei189 – 209HelicalSequence 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 – 73LRL → AAA: Significantly accumulates in the nucleus. Increases apoptotic activity. Does not interact with XPO1. 1 Publication3

Organism-specific databases

DisGeNETi666.
OpenTargetsiENSG00000176720.
PharmGKBiPA25396.

Polymorphism and mutation databases

BioMutaiBOK.
DMDMi57012554.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430861 – 212Bcl-2-related ovarian killer proteinAdd BLAST212

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-linki159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki176Glycyl 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 pro-apoptotic activity; promotes degradation of newly synthesized proteins that are not ITPR1 associated.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UMX3.
PaxDbiQ9UMX3.
PeptideAtlasiQ9UMX3.
PRIDEiQ9UMX3.

PTM databases

iPTMnetiQ9UMX3.
PhosphoSitePlusiQ9UMX3.

Expressioni

Tissue specificityi

Expressed mainly in oocytes; weak expression in granulosa cells of the developing follicles. In adult human ovaries, expressed in granulosa cells at all follicular stages, but expression in primordial/primary follicles granulosa cell is stronger than in secondary and antral follicles.1 Publication

Developmental stagei

Isoform 1: at 5-7 weeks of gestation, detected primarily in the cytotrophoblast layer. By 10-13 weeks, expression becomes restricted primarily to the apical border of the syncytiotrophoblast (PubMed:19942931). Isoform 2: expression significantly increased around 6-8 weeks (PubMed:15775999).2 Publications

Inductioni

Up-regulated by DNA damage.1 Publication

Gene expression databases

BgeeiENSG00000176720.
CleanExiHS_BOK.
ExpressionAtlasiQ9UMX3. baseline and differential.
GenevisibleiQ9UMX3. HS.

Interactioni

Subunit structurei

Monomer; positively regulates apoptotic process. Homodimer (By similarity). Heterodimer (By similarity). Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation (PubMed:15868100). 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:23884412). 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 (PubMed:16302269). Interacts with BNIP3; promotes oligomerization (PubMed:15868100).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107134. 6 interactors.
IntActiQ9UMX3. 1 interactor.
STRINGi9606.ENSP00000314132.

Structurei

3D structure databases

ProteinModelPortaliQ9UMX3.
SMRiQ9UMX3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 45Interactions with ITPR1By similarityAdd BLAST31
Regioni70 – 78Nuclear export signal1 Publication9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 44BH4Add BLAST13
Motifi66 – 82BH3Add BLAST17
Motifi112 – 131BH1Add BLAST20
Motifi164 – 178BH2Add 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.
HOVERGENiHBG050709.
InParanoidiQ9UMX3.
KOiK02561.
OMAiCVRHGHP.
OrthoDBiEOG091G0JPB.
PhylomeDBiQ9UMX3.
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: Q9UMX3-1) [UniParc]FASTAAdd to basket
Also known as: Mtd-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
SAPERAAPVP GRLAEVCAVL LRLGDELEMI RPSVYRNVAR QLHISLQSEP
110 120 130 140 150
VVTDAFLAVA GHIFSAGITW GKVVSLYAVA AGLAVDCVRQ AQPAMVHALV
160 170 180 190 200
DCLGEFVRKT LATWLRRRGG WTDVLKCVVS TDPGLRSHWL VAALCSFGRF
210
LKAAFFVLLP ER
Length:212
Mass (Da):23,280
Last modified:May 1, 2000 - v1
Checksum:i053ED605FF8EF5B2
GO
Isoform 2 (identifier: Q9UMX3-2) [UniParc]FASTAAdd to basket
Also known as: Mtd-P1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-78: Missing.

Show »
Length:134
Mass (Da):14,721
Checksum:iE867DD4B4D049D4F
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0585991 – 78Missing in isoform 2. Add BLAST78

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF174487 mRNA. Translation: AAD51719.1.
BT007272 mRNA. Translation: AAP35936.1.
BC006203 mRNA. No translation available.
CCDSiCCDS2550.1. [Q9UMX3-1]
RefSeqiNP_115904.1. NM_032515.4. [Q9UMX3-1]
XP_011509998.1. XM_011511696.2. [Q9UMX3-1]
XP_016860264.1. XM_017004775.1. [Q9UMX3-2]
XP_016860265.1. XM_017004776.1. [Q9UMX3-2]
UniGeneiHs.293753.
Hs.734656.

Genome annotation databases

EnsembliENST00000318407; ENSP00000314132; ENSG00000176720. [Q9UMX3-1]
GeneIDi666.
KEGGihsa:666.
UCSCiuc002wbq.4. human. [Q9UMX3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiBOK_HUMAN
AccessioniPrimary (citable) accession number: Q9UMX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: May 1, 2000
Last modified: October 25, 2017
This is version 131 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families