BOK_RAT
ID BOK_RAT Reviewed; 213 AA.
AC Q792S6; O88857;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Bcl-2-related ovarian killer protein {ECO:0000303|PubMed:9356461};
GN Name=Bok {ECO:0000312|RGD:70984};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP FUNCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Ovary;
RX PubMed=9356461; DOI=10.1073/pnas.94.23.12401;
RA Hsu S.Y., Kaipia A., McGee E., Lomeli M., Hsueh A.J.W.;
RT "Bok is a pro-apoptotic Bcl-2 protein with restricted expression in
RT reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-
RT 2 family members.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:12401-12406(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, PROTEIN
RP HETERODIMERIZATION, SUBUNIT, AND MUTAGENESIS OF 71-LEU--LEU-74;
RP 75-GLY--GLU-77 AND GLY-75.
RX PubMed=9804769; DOI=10.1074/jbc.273.46.30139;
RA Hsu S.Y., Hsueh A.J.;
RT "A splicing variant of the Bcl-2 member Bok with a truncated BH3 domain
RT induces apoptosis but does not dimerize with antiapoptotic Bcl-2 proteins
RT in vitro.";
RL J. Biol. Chem. 273:30139-30146(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Apoptosis regulator that functions through different
CC apoptotic signaling pathways (PubMed:9356461, PubMed:9804769). Plays a
CC roles as pro-apoptotic protein that positively regulates intrinsic
CC apoptotic process in a BAX- and BAK1-dependent manner or in a BAX- and
CC BAK1-independent manner (By similarity). In response to endoplasmic
CC reticulum stress promotes mitochondrial apoptosis through downstream
CC BAX/BAK1 activation and positive regulation of PERK-mediated unfolded
CC protein response (By similarity). Activates apoptosis independently of
CC heterodimerization with survival-promoting BCL2 and BCL2L1 through
CC induction of mitochondrial outer membrane permeabilization, in a
CC BAX- and BAK1-independent manner, in response to inhibition of ERAD-
CC proteasome degradation system, resulting in cytochrome c release (By
CC similarity). In response to DNA damage, mediates intrinsic apoptotic
CC process in a TP53-dependent manner. Plays a role in granulosa cell
CC apoptosis by CASP3 activation (By similarity). Plays a roles as anti-
CC apoptotic protein during neuronal apoptotic process, by negatively
CC regulating poly ADP-ribose polymerase-dependent cell death through
CC regulation of neuronal calcium homeostasis and mitochondrial
CC bioenergetics in response to NMDA excitation (By similarity). In
CC addition to its role in apoptosis, may regulate trophoblast cell
CC proliferation during the early stages of placental development, by
CC acting on G1/S transition through regulation of CCNE1 expression. May
CC also play a role as an inducer of autophagy by disrupting interaction
CC between MCL1 and BECN1 (By similarity). {ECO:0000250|UniProtKB:O35425,
CC ECO:0000250|UniProtKB:Q9UMX3, ECO:0000269|PubMed:9356461,
CC ECO:0000269|PubMed:9804769}.
CC -!- FUNCTION: [Isoform 2]: Positively regulates apoptotic process in an
CC heterodimerization-independent manner with antiapoptotic Bcl-2
CC proteins. {ECO:0000269|PubMed:9804769}.
CC -!- SUBUNIT: Isoform 1: Honomer; positively regulates apoptotic process.
CC Homodimer (By similarity). Heterodimer (PubMed:9804769). Oligomer;
CC promoted by apoptotic stimuli and BH3-only proteins; mediates
CC constitutive activation. Interacts (via BH4 domain) with ITPR1;
CC enhances BOK expression and stabilization; limits apoptosis and
CC prevents ubiquitination and then degradation; protects ITPR1 from
CC proteolysis by CASP3 during apoptosis. Interacts with ITPR2 AND ITPR3;
CC binds most strongly to ITPR2, and barely to ITPR3; regulates their
CC expression (By similarity). Interacts with XPO1; translocates to the
CC cytoplasm. Interacts with BNIP3; promotes oligomerization (By
CC similarity). Isoform 2: Does not heterodimerize with antiapoptotic Bcl-
CC 2 proteins (PubMed:9804769). {ECO:0000250|UniProtKB:O35425,
CC ECO:0000250|UniProtKB:Q9UMX3, ECO:0000269|PubMed:9804769}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000250|UniProtKB:O35425}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O35425}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9UMX3}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O35425}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9UMX3}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UMX3}. Nucleus {ECO:0000250|UniProtKB:Q9UMX3}.
CC Mitochondrion {ECO:0000250|UniProtKB:Q9UMX3}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9UMX3}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9UMX3}. Early endosome membrane
CC {ECO:0000250|UniProtKB:O35425}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:O35425}. Nucleus outer membrane
CC {ECO:0000250|UniProtKB:O35425}. Golgi apparatus, cis-Golgi network
CC membrane {ECO:0000250|UniProtKB:O35425}. Golgi apparatus, trans-Golgi
CC network membrane {ECO:0000250|UniProtKB:O35425}. Membrane
CC {ECO:0000250|UniProtKB:Q9UMX3}. Note=Nuclear and cytoplasmic
CC compartments in the early stages of apoptosis and during apoptosis it
CC associates with mitochondria. In healthy cells, associates loosely with
CC the membrane in a hit-and-run mode. The insertion and accumulation on
CC membranes is enhanced through the activity of death signals, resulting
CC in the integration of the membrane-bound protein into the membrane (By
CC similarity). The transmembrane domain controls subcellular
CC localization; constitutes a tail-anchor. Localizes in early and late
CC endosome upon blocking of apoptosis. Must localize to the mitochondria
CC to induce mitochondrial outer membrane permeabilization and apoptosis
CC (By similarity). {ECO:0000250|UniProtKB:O35425,
CC ECO:0000250|UniProtKB:Q9UMX3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Bok-L {ECO:0000303|PubMed:9804769};
CC IsoId=Q792S6-1; Sequence=Displayed;
CC Name=2; Synonyms=Bok-S {ECO:0000303|PubMed:9804769};
CC IsoId=Q792S6-2; Sequence=VSP_012447;
CC -!- TISSUE SPECIFICITY: Expressed in ovary, testis and uterus.
CC {ECO:0000269|PubMed:9356461}.
CC -!- DOMAIN: BH4 domain mediates interaction with ITPR1.
CC {ECO:0000250|UniProtKB:O35425}.
CC -!- PTM: Ubiquitinated by AMFR/gp78 E3 ubiquitin ligase complex; mediates
CC degradation by ubiquitin-proteasome pathway in a VCP/p97-dependent
CC manner; prevents from proapoptotic activity; promotes degradation of
CC newly synthesized proteins that are not ITPR1 associated.
CC {ECO:0000250|UniProtKB:O35425}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AF027954; AAB87418.1; -; mRNA.
DR EMBL; AF051093; AAC61928.1; -; mRNA.
DR EMBL; BC078871; AAH78871.1; -; mRNA.
DR RefSeq; NP_059008.1; NM_017312.2. [Q792S6-1]
DR RefSeq; XP_017451805.1; XM_017596316.1. [Q792S6-1]
DR AlphaFoldDB; Q792S6; -.
DR SMR; Q792S6; -.
DR STRING; 10116.ENSRNOP00000024693; -.
DR PhosphoSitePlus; Q792S6; -.
DR PaxDb; Q792S6; -.
DR Ensembl; ENSRNOT00000024526; ENSRNOP00000024526; ENSRNOG00000018214. [Q792S6-2]
DR Ensembl; ENSRNOT00000024695; ENSRNOP00000024693; ENSRNOG00000018214. [Q792S6-1]
DR GeneID; 29884; -.
DR KEGG; rno:29884; -.
DR UCSC; RGD:70984; rat. [Q792S6-1]
DR CTD; 666; -.
DR RGD; 70984; Bok.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244872; -.
DR HOGENOM; CLU_114994_0_0_1; -.
DR InParanoid; Q792S6; -.
DR OMA; DMTKCVV; -.
DR OrthoDB; 1278637at2759; -.
DR PhylomeDB; Q792S6; -.
DR TreeFam; TF315834; -.
DR PRO; PR:Q792S6; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000018214; Expressed in ovary and 19 other tissues.
DR Genevisible; Q792S6; RN.
DR GO; GO:0033106; C:cis-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:RGD.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0051400; F:BH domain binding; IPI:RGD.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISO:RGD.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; ISO:RGD.
DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1903899; P:positive regulation of PERK-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISO:RGD.
DR GO; GO:1901382; P:regulation of chorionic trophoblast cell proliferation; ISS:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:1904708; P:regulation of granulosa cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:RGD.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR026309; BOK.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF48; PTHR11256:SF48; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasm; Endoplasmic reticulum;
KW Endosome; Golgi apparatus; Isopeptide bond; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Mitochondrion outer membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..213
FT /note="Bcl-2-related ovarian killer protein"
FT /id="PRO_0000143088"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 15..45
FT /note="Interactions with ITPR1"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT REGION 71..79
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q9UMX3"
FT MOTIF 32..44
FT /note="BH4"
FT MOTIF 67..83
FT /note="BH3"
FT MOTIF 113..132
FT /note="BH1"
FT MOTIF 165..179
FT /note="BH2"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT CROSSLNK 32
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT CROSSLNK 160
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT CROSSLNK 177
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O35425"
FT VAR_SEQ 75..117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9356461"
FT /id="VSP_012447"
FT MUTAGEN 71..74
FT /note="LLRL->GGGG: Retains proapoptotic activity. Does not
FT heterodimerizes."
FT /evidence="ECO:0000269|PubMed:9804769"
FT MUTAGEN 75..77
FT /note="GDE->AAA: Retains proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:9804769"
FT MUTAGEN 75
FT /note="G->A: Retains proapoptotic activity."
FT /evidence="ECO:0000269|PubMed:9804769"
SQ SEQUENCE 213 AA; 23456 MW; F8755C45CB05D626 CRC64;
MEVLRRSSVF AAEIMDAFDR SPTDKELVAQ AKALGREYVH ARLLRAGLSW SAPERASPAP
GGRLAEVCTV LLRLGDELEQ IRPSVYRNVA RQLHIPLQSE PVVTDAFLAV AGHIFSAGIT
WGKVVSLYSV AAGLAVDCVR QAQPAMVHAL VDCLGEFVRK TLATWLRRRG GWTDVLKCVV
STDPGFRSHW LVATLCSFGR FLKAAFFLLL PER
