Human Gene BCL2 (ENST00000398117.1) Description and Page Index
Description: Homo sapiens BCL2 apoptosis regulator (BCL2), transcript variant alpha, mRNA. (from RefSeq NM_000633) RefSeq Summary (NM_000633): This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]. Gencode Transcript: ENST00000398117.1 Gencode Gene: ENSG00000171791.13 Transcript (Including UTRs) Position: hg38 chr18:63,123,346-63,320,128 Size: 196,783 Total Exon Count: 2 Strand: - Coding Region Position: hg38 chr18:63,128,625-63,318,666 Size: 190,042 Coding Exon Count: 2
ID:BCL2_HUMAN DESCRIPTION: RecName: Full=Apoptosis regulator Bcl-2; 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). 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. INTERACTION: Self; NbExp=3; IntAct=EBI-77694, EBI-77694; Q92934:BAD; NbExp=5; IntAct=EBI-77694, EBI-700771; Q61337:Bad (xeno); NbExp=6; IntAct=EBI-77694, EBI-400328; Q07812:BAX; NbExp=8; 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=4; 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; Q14457:BECN1; NbExp=3; 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; 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=3; IntAct=EBI-77694, EBI-366083; SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. TISSUE SPECIFICITY: Expressed in a variety of tissues. DOMAIN: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3. 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). 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. PTM: Monoubiquitinated by PARK2, leading to increase its stability. 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. SIMILARITY: Belongs to the Bcl-2 family. 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";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P10415
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.