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MitoProteome Human Mitochondrial Protein Database
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Related Proteins
MT000076
UniProt Annotations
Entry Information
Gene Name
B-cell CLL/lymphoma 2
Protein Entry
BCL2_HUMAN
UniProt ID
P10415
Species
Human
Comments
Comment type
Description
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=Alpha; IsoId=P10415-1; Sequence=Displayed; Name=Beta; IsoId=P10415-2; Sequence=VSP_000512; Note=Ref.1 (AAA51814) sequence is in conflict in position: 199:L->S. {ECO:0000305};
Disease
Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
Domain
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
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). {ECO:0000269|PubMed:18570871}.
Interaction
Self; NbExp=3; IntAct=EBI-77694, EBI-77694; Q9C0C7:AMBRA1; NbExp=10; IntAct=EBI-77694, EBI-2512975; Q92934:BAD; NbExp=5; IntAct=EBI-77694, EBI-700771; Q61337:Bad (xeno); NbExp=6; IntAct=EBI-77694, EBI-400328; Q07812:BAX; NbExp=9; IntAct=EBI-77694, EBI-516580; Q9BXH1:BBC3; NbExp=5; IntAct=EBI-77694, EBI-519884; P51572:BCAP31; NbExp=2; IntAct=EBI-77694, EBI-77683; O43521:BCL2L11; NbExp=7; IntAct=EBI-77694, EBI-526406; O43521-1:BCL2L11; NbExp=3; IntAct=EBI-77694, EBI-526416; O43521-2:BCL2L11; NbExp=4; IntAct=EBI-77694, EBI-526420; Q9NYF8:BCLAF1; NbExp=2; IntAct=EBI-77694, EBI-437804; Q14457:BECN1; NbExp=16; IntAct=EBI-77694, EBI-949378; P55957:BID; NbExp=8; IntAct=EBI-77694, EBI-519672; Q13323:BIK; NbExp=3; IntAct=EBI-77694, EBI-700794; Q91ZE9:Bmf (xeno); NbExp=2; IntAct=EBI-77694, EBI-708032; O60238:BNIP3L; NbExp=2; IntAct=EBI-77694, EBI-849893; P38398:BRCA1; NbExp=6; IntAct=EBI-77694, EBI-349905; O15151:MDM4; NbExp=4; IntAct=EBI-77694, EBI-398437; Q96HR8:NAF1; NbExp=2; IntAct=EBI-77694, EBI-2515597; Q9C000:NLRP1; NbExp=12; IntAct=EBI-77694, EBI-1220518; P22736:NR4A1; NbExp=7; IntAct=EBI-77694, EBI-721550; Q13794:PMAIP1; NbExp=3; IntAct=EBI-77694, EBI-707392; O15304:SIVA1; NbExp=2; IntAct=EBI-77694, EBI-520756; P04637:TP53; NbExp=5; IntAct=EBI-77694, EBI-366083; Q13625:TP53BP2; NbExp=13; IntAct=EBI-77694, EBI-77642;
Ptm
Monoubiquitinated by PARK2, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome. {ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:23431138}.
Ptm
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. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity). {ECO:0000250}.
Ptm
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. {ECO:0000269|PubMed:9395403}.
Similarity
Belongs to the Bcl-2 family. {ECO:0000305}.
Subcellular Location
Mitochondrion outer membrane {ECO:0000269|PubMed:2250705}; Single-pass membrane protein {ECO:0000269|PubMed:2250705}. Nucleus membrane {ECO:0000269|PubMed:2250705}; Single-pass membrane protein {ECO:0000269|PubMed:2250705}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:2250705}; Single-pass membrane protein {ECO:0000269|PubMed:2250705}.
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). 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 BOP. Interacts with the SCF(FBXO10) complex. {ECO:0000250, ECO:0000269|PubMed:11463391, ECO:0000269|PubMed:12901880, ECO:0000269|PubMed:15547950, ECO:0000269|PubMed:15733859, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:17090549, ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:19706769, ECO:0000269|PubMed:20849813, ECO:0000269|PubMed:23055042, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:8668206, ECO:0000269|PubMed:9305631}.
Tissue Specificity
Expressed in a variety of tissues.
Web Resource
Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BCL2ID49.html";
Web Resource
Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/bcl2/";
Web Resource
Name=Wikipedia; Note=Bcl-2 entry; URL="http://en.wikipedia.org/wiki/Bcl-2";
MitoProteome Human Mitochondrial Protein Database
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