Predicate | Object |
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rdf:type | |
biopax3:comment |
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. 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 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"; GENE SYNONYMS:BCL2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.,
SEQUENCE 239 AA; 26266 MW; 3C49F2B714DC9CCB CRC64;
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biopax3:xref |
urn:biopax:RelationshipXref:HGNC_HGNC:990,
urn:biopax:RelationshipXref:NCBI GENE_596,
urn:biopax:RelationshipXref:REFSEQ_NP_000624,
urn:biopax:UnificationXref:UNIPROT_P10415,
urn:biopax:UnificationXref:UNIPROT_P10416,
urn:biopax:UnificationXref:UNIPROT_Q13842,
urn:biopax:UnificationXref:UNIPROT_Q16197
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biopax3:displayName |
BCL2_HUMAN
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biopax3:name |
BCL2
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biopax3:entityFeature | |
biopax3:organism | |
biopax3:sequence |
MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK
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biopax3:standardName |
Apoptosis regulator Bcl-2
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