BOK

The protein encoded by this gene belongs to the BCL2 family, members of which form homo- or heterodimers, and act as anti- or proapoptotic regulators that are involved in a wide variety of cellular processes.

BCL2 family apoptosis regulator BOK

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 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 (PubMed:19942931).
May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1 (PubMed:24113155).
Isoform 2: Pro-apoptotic molecule exerting its function through the mitochondrial pathway.

Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Source: UniProtKB
Apoptotic process Source: UniProtKB
Brain development Source: Ensembl
Cellular component disassembly involved in execution phase of apoptosis Source: UniProtKB
Extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
Intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
Male gonad development Source: Ensembl
Negative regulation of mitochondrial depolarization Source: Ensembl
Negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: Ensembl
Negative regulation of necroptotic process Source: Ensembl
Negative regulation of neuron apoptotic process Source: Ensembl
Neuron apoptotic process Source: Ensembl
Oligodendrocyte differentiation Source: Ensembl
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of execution phase of apoptosis Source: UniProtKB
Positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway Source: UniProtKB
Positive regulation of PERK-mediated unfolded protein response Source: UniProtKB
Protein complex oligomerization Source: UniProtKB
Regulation of autophagy Source: UniProtKB
Regulation of chorionic trophoblast cell proliferation Source: UniProtKB
Regulation of cytosolic calcium ion concentration Source: Ensembl
Regulation of granulosa cell apoptotic process Source: UniProtKB
Release of cytochrome c from mitochondria Source: UniProtKB

Isoform 1: Endoplasmic reticulum membrane; Endoplasmic reticulum; Cis-Golgi network membrane; Trans-Golgi network membrane; Early endosome membrane; Recycling endosome membrane; Nucleus; Nucleus outer membrane; Mitochondrion membrane; Mitochondrion inner membrane; Mitochondrion; Mitochondrion outer membrane; Cytoplasm; Membrane. Nuclear and cytoplasmic compartments in the early stages of apoptosis and during apoptosis it associates with mitochondria (PubMed:19942931). 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 (PubMed:15868100). 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).
Isoform 2: Cytoplasm; Membrane

Helical: 189-209 aa

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.