CPATH-140846

cpath:CPATH-LOCAL-580466, cpath:CPATH-LOCAL-580466, cpath:CPATH-LOCAL-580467, cpath:CPATH-LOCAL-580467, cpath:CPATH-LOCAL-580468, cpath:CPATH-LOCAL-580468, cpath:CPATH-LOCAL-580469, cpath:CPATH-LOCAL-580469, cpath:CPATH-LOCAL-580470, cpath:CPATH-LOCAL-580470, cpath:CPATH-LOCAL-580471, cpath:CPATH-LOCAL-580471, cpath:CPATH-LOCAL-580472, cpath:CPATH-LOCAL-580472, cpath:CPATH-LOCAL-581482, cpath:CPATH-LOCAL-581482

BCL2_HUMAN, BCL2_HUMAN

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). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, MRPL41, RAF-1 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. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=Alpha; IsoId=P10415-1; Sequence=Displayed; Name=Beta; IsoId=P10415-2; Sequence=VSP_000512; TISSUE SPECIFICITY: Expressed in a variety of tissues. DOMAIN: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF-1. 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. 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"; COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., 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). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, MRPL41, RAF-1 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. SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=Alpha; IsoId=P10415-1; Sequence=Displayed; Name=Beta; IsoId=P10415-2; Sequence=VSP_000512; TISSUE SPECIFICITY: Expressed in a variety of tissues. DOMAIN: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF-1. 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. 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"; COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.

entrez-gene:596