Q6R755 · BCL2_CANLF
- ProteinApoptosis regulator Bcl-2
- GeneBCL2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids236 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score4/5
Function
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.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 64-65 | Cleavage; by caspase-3 and caspase-9 | ||||
Sequence: DM |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | mitochondrial outer membrane | |
Cellular Component | nuclear membrane | |
Molecular Function | BH domain binding | |
Biological Process | autophagy | |
Biological Process | extrinsic apoptotic signaling pathway in absence of ligand | |
Biological Process | intrinsic apoptotic signaling pathway in response to DNA damage | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | negative regulation of autophagy | |
Biological Process | release of cytochrome c from mitochondria |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameApoptosis regulator Bcl-2
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionQ6R755
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion outer membrane ; Single-pass membrane protein
Nucleus membrane ; Single-pass membrane protein
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 209-230 | Helical | ||||
Sequence: FSWLSLKALLSLALVGACITLG |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000289601 | 1-236 | Apoptosis regulator Bcl-2 | |||
Sequence: MAQAGRTGYDNREIVMKYIHYKLSQRGYEWDVGDVDAAPLGAAPTPGIFSFQPESNPTPAVHRDMAARTSPLRPIVATTGPTLSPVPPVVHLTLRRAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGWDAFVELYGPTMQPLFDFSWLSLKALLSLALVGACITLGAYLGHK | ||||||
Modified residue | 69 | Phosphothreonine; by MAPK8 | ||||
Sequence: T | ||||||
Modified residue | 70 | Phosphoserine; by MAPK8 and PKC | ||||
Sequence: S | ||||||
Modified residue | 84 | Phosphoserine; by MAPK8 | ||||
Sequence: S |
Post-translational modification
Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle (By similarity).
In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases (By similarity).
Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, which stimulates starvation-induced autophagy (By similarity).
Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).
In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases (By similarity).
Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, which stimulates starvation-induced autophagy (By similarity).
Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity (By similarity).
Monoubiquitinated by PRKN, leading to an increase in its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.
Keywords
- PTM
Interaction
Subunit
Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity).
Component of the complex, at least composed of LRPPRC, BECN1 and BCL2; the interactions prevent BECN1 from forming an autophagy-inducing complex with PIK3C3 (By similarity).
Interacts with EI24 (By similarity).
Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP. Interacts with the SCF(FBXO10) complex. Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (By similarity).
Interacts with GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity).
Interacts with BCAP31. Interacts with IRF3; the interaction is inhibited by Sendai virus infection. Interacts with BECN1; thereby inhibiting autophagy in non-starvation conditions. Interacts with AMBRA1; thereby inhibiting autophagy (By similarity).
Component of the complex, at least composed of LRPPRC, BECN1 and BCL2; the interactions prevent BECN1 from forming an autophagy-inducing complex with PIK3C3 (By similarity).
Interacts with EI24 (By similarity).
Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP. Interacts with the SCF(FBXO10) complex. Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (By similarity).
Interacts with GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity).
Interacts with BCAP31. Interacts with IRF3; the interaction is inhibited by Sendai virus infection. Interacts with BECN1; thereby inhibiting autophagy in non-starvation conditions. Interacts with AMBRA1; thereby inhibiting autophagy (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 10-30 | BH4 | ||||
Sequence: DNREIVMKYIHYKLSQRGYEW | ||||||
Motif | 90-104 | BH3 | ||||
Sequence: VHLTLRRAGDDFSRR | ||||||
Motif | 133-152 | BH1 | ||||
Sequence: ELFRDGVNWGRIVAFFEFGG | ||||||
Motif | 184-199 | BH2 | ||||
Sequence: TWIQDNGGWDAFVELY |
Domain
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.
The BH3 motif is required for XIAP-mediated ubiquitination and subsequent induction of apoptosis.
Sequence similarities
Belongs to the Bcl-2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length236
- Mass (Da)26,449
- Last updated2004-07-05 v1
- ChecksumBC22E0CEFD3EB228
Keywords
- Technical term