Apoptosis regulator Bcl-2
Also known as: BCL2
Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function. May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release.
Classification
- Family (Pfam)
- PF00452 Bcl-2, PF02180 BH4
- InterPro
- Apop_reg_Bcl2, Bcl-2-like_sf, Bcl-2_BH1-3, Bcl-2_fam, Bcl2-like, Bcl2/BclX, Bcl2_BH1_motif_CS, Bcl2_BH2_motif_CS, Bcl2_BH3_motif_CS, Bcl2_BH4, Bcl2_BH4_motif_CS
- Functional cluster
- Membrane Channels & Lipid-Anchored Proteins
Experimental structures · PDB · 46
- 1G5M NMR
- 1GJH NMR
- 1YSW NMR
- 2O21 NMR
- 2O22 NMR
- 2O2F NMR
- 2W3L X-ray 2.10A
- 2XA0 X-ray 2.70A
- 4AQ3 X-ray 2.40A
- 4IEH X-ray 2.10A
- 4LVT X-ray 2.05A
- 4LXD X-ray 1.90A
- … and 34 more
A predicted model is available from AlphaFold.
Gene Ontology · 66
- GO:0097136 Bcl-2 family protein complex
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005783 endoplasmic reticulum
- GO:0005789 endoplasmic reticulum membrane
- GO:0016020 membrane
- GO:0005741 mitochondrial outer membrane
- GO:0005739 mitochondrion
- GO:0043209 myelin sheath
- GO:0031965 nuclear membrane
- GO:0005634 nucleus
- GO:0046930 pore complex
- GO:0032991 protein-containing complex
- GO:0051434 BH3 domain binding
- GO:0015267 channel activity
- GO:0016248 channel inhibitor activity
- GO:0140297 DNA-binding transcription factor binding
- GO:0042802 identical protein binding
- GO:0060090 molecular adaptor activity
- GO:0002020 protease binding
- GO:0046982 protein heterodimerization activity
- GO:0051721 protein phosphatase 2A binding
- GO:0043565 sequence-specific DNA binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0006915 apoptotic process
- GO:0006914 autophagy
- GO:0042100 B cell proliferation
- GO:0050853 B cell receptor signaling pathway
- GO:0051607 defense response to virus
- GO:0006974 DNA damage response
- GO:0032469 endoplasmic reticulum calcium ion homeostasis
- GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
- GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
- GO:0007565 female pregnancy
- GO:0031069 hair follicle morphogenesis
- GO:0006959 humoral immune response
- GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
- GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- GO:2000811 negative regulation of anoikis
- GO:0043066 negative regulation of apoptotic process
- GO:2001234 negative regulation of apoptotic signaling pathway
- GO:0010507 negative regulation of autophagy
- GO:0032848 negative regulation of cellular pH reduction
- GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
- GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- GO:0051902 negative regulation of mitochondrial depolarization
- GO:0043524 negative regulation of neuron apoptotic process
- GO:0051402 neuron apoptotic process
- GO:0043473 pigmentation
- GO:0043065 positive regulation of apoptotic process
- GO:0030890 positive regulation of B cell proliferation
- GO:0030307 positive regulation of cell growth
- GO:0008284 positive regulation of cell population proliferation
- GO:0000209 protein polyubiquitination
- GO:0051924 regulation of calcium ion transport
- GO:0046902 regulation of mitochondrial membrane permeability
- GO:0051881 regulation of mitochondrial membrane potential
- GO:0045069 regulation of viral genome replication
- GO:0001836 release of cytochrome c from mitochondria
- GO:0034097 response to cytokine
- GO:0010039 response to iron ion
- GO:0035094 response to nicotine
- GO:0009314 response to radiation
- GO:0009636 response to toxic substance
- GO:0009410 response to xenobiotic stimulus
Drugs targeting this protein · 3
- OBATOCLAX MESYLATE inhibitor
- VENETOCLAX inhibitor
- NAVITOCLAX inhibitor
Related proteins · sequence + function similarity
- Apoptosis regulator Bcl-2 0.97
- Apoptosis regulator Bcl-2 0.97
- Apoptosis regulator Bcl-2 0.95
- Apoptosis regulator Bcl-2 0.95
- Apoptosis regulator Bcl-2 0.95
- Apoptosis regulator Bcl-2 0.94
- Bcl-2 homologous antagonist/killer 0.75
- Bcl-2-like protein 1 0.72
- Bcl-2-like protein 1 0.71
- Bcl-2-like protein 1 0.70
- Bcl-2-like protein 1 0.70
- Bcl-2-like protein 2 0.68
Co-cited proteins · studied together in the literature
- G0/G1 switch protein 2 1 shared papers
- Serine/threonine-protein kinase ROP17 1 shared papers
- Peptidyl-prolyl cis-trans isomerase FKBP8 2 shared papers
- Large ribosomal subunit protein mL41 1 shared papers
- Bcl-2-like protein 1 5 shared papers
- Apoptosis regulator Bcl-2 1 shared papers
- Apoptosis regulator Bcl-2 3 shared papers
- Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein 1 shared papers
- Apoptosis-stimulating of p53 protein 2 1 shared papers
- Rho GTPase-activating protein 1 1 shared papers
- Prolyl hydroxylase EGLN3 1 shared papers
- Beclin-1 3 shared papers
Literature · 39 cited papers
- Toxoplasma gondii ROP17 promotes autophagy via the Bcl-2-Beclin 1 pathway. Folia Parasitol. · 2021
- BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites. Sci. Adv. · 2019
- Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. Cell Rep. · 2017
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- Tom70 mediates Sendai virus-induced apoptosis on mitochondria. J. Virol. · 2015
- Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability. Biochem. J. · 2013
- Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc. Natl. Acad. Sci. U.S.A. · 2013
- Human Bop is a novel BH3-only member of the Bcl-2 protein family. Protein Cell · 2012
- Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J. · 2011
- Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J. Biol. Chem. · 2010
- Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells. Biochem. Biophys. Res. Commun. · 2010
- Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer Res. · 2009
- … and 27 more in the literature graph
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