Q6R755 · BCL2_CANLF

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.

123620406080100120140160180200220
TypeIDPosition(s)Description
Site64-65Cleavage; by caspase-3 and caspase-9

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmitochondrial outer membrane
Cellular Componentnuclear membrane
Molecular FunctionBH domain binding
Biological Processautophagy
Biological Processextrinsic apoptotic signaling pathway in absence of ligand
Biological Processintrinsic apoptotic signaling pathway in response to DNA damage
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of autophagy
Biological Processrelease of cytochrome c from mitochondria

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Apoptosis regulator Bcl-2

Gene names

    • Name
      BCL2

Organism names

Accessions

  • Primary accession
    Q6R755

Proteomes

Subcellular Location

Mitochondrion outer membrane
; Single-pass membrane protein
Nucleus membrane
; Single-pass membrane protein
Endoplasmic reticulum membrane
; Single-pass membrane protein
Cytoplasm

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane209-230Helical

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002896011-236Apoptosis regulator Bcl-2
Modified residue69Phosphothreonine; by MAPK8
Modified residue70Phosphoserine; by MAPK8 and PKC
Modified residue84Phosphoserine; by MAPK8

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).
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

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).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for motif.

TypeIDPosition(s)Description
Motif10-30BH4
Motif90-104BH3
Motif133-152BH1
Motif184-199BH2

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    236
  • Mass (Da)
    26,449
  • Last updated
    2004-07-05 v1
  • Checksum
    BC22E0CEFD3EB228
MAQAGRTGYDNREIVMKYIHYKLSQRGYEWDVGDVDAAPLGAAPTPGIFSFQPESNPTPAVHRDMAARTSPLRPIVATTGPTLSPVPPVVHLTLRRAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGWDAFVELYGPTMQPLFDFSWLSLKALLSLALVGACITLGAYLGHK

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY509563
EMBL· GenBank· DDBJ
AAR92491.1
EMBL· GenBank· DDBJ
mRNA

Similar Proteins

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