ID BCL2_CANFA Reviewed; 236 AA. AC Q6R755; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 04-NOV-2008, entry version 29. DE RecName: Full=Apoptosis regulator Bcl-2; GN Name=BCL2; OS Canis familiaris (Dog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; OC Canis. OX NCBI_TaxID=9615; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Chien M.B., London C.A., Jones C.S.; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Suppresses apoptosis in a variety of cell systems CC including factor-dependent lymphohematopoietic and neural cells. CC Regulates cell death by controlling the mitochondrial membrane CC permeability. Appears to function in a feedback loop system with CC caspases. Inhibits caspase activity either by preventing the CC release of cytochrome c from the mitochondria and/or by binding to CC the apoptosis-activating factor (APAF-1) (By similarity). CC -!- SUBUNIT: Forms homodimers, and heterodimers with BAX, BAD, BAK and CC Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 CC motifs, and is necessary for anti-apoptotic activity. Also CC interacts with FKBP8, APAF1, RAF-1, TP53BP2, BBC3, BCL2L1, MRPL41 CC and BNIPL (By similarity). CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass CC membrane protein (By similarity). Nucleus membrane; Single-pass CC membrane protein (By similarity). Endoplasmic reticulum membrane; CC Single-pass membrane protein (By similarity). CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and CC for interaction with RAF-1 (By similarity). CC -!- PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti- CC apoptotic activity. Growth factor-stimulated phosphorylation on CC Ser-70 by PKC is required for the anti-apoptosis activity and CC occurs during the G2/M phase of the cell cycle (By similarity). In CC the absence of growth factors, BCL2 appears to be phosphorylated CC by other protein kinases such as ERKs and stress-activated kinases CC (By similarity). Dephosphorylated by protein phosphatase 2A (PP2A) CC (By similarity). CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The CC cleaved protein, lacking the BH4 motif, has pro-apoptotic CC activity, causes the release of cytochrome c into the cytosol CC promoting further caspase activity (By similarity). CC -!- SIMILARITY: Belongs to the Bcl-2 family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY509563; AAR92491.1; -; mRNA. DR UniGene; Cfa.110; -. DR HSSP; P53563; 1AF3. DR SMR; Q6R755; 41-204. DR HOVERGEN; Q6R755; -. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-KW. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR InterPro; IPR013278; Apop_reg_Bcl2. DR InterPro; IPR002475; BCL2_apoptsis. DR InterPro; IPR000712; Bcl2_BH. DR InterPro; IPR003093; Bcl2_BH4. DR InterPro; IPR004725; Bcl2_reg. DR Pfam; PF00452; Bcl-2; 1. DR Pfam; PF02180; BH4; 1. DR PRINTS; PR01863; APOPREGBCL2. DR PRINTS; PR01862; BCL2FAMILY. DR SMART; SM00337; BCL; 1. DR SMART; SM00265; BH4; 1. DR TIGRFAMs; TIGR00865; bcl-2; 1. DR PROSITE; PS50062; BCL2_FAMILY; 1. DR PROSITE; PS01080; BH1; 1. DR PROSITE; PS01258; BH2; 1. DR PROSITE; PS01259; BH3; 1. DR PROSITE; PS01260; BH4_1; 1. DR PROSITE; PS50063; BH4_2; 1. PE 2: Evidence at transcript level; KW Apoptosis; Endoplasmic reticulum; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Transmembrane. FT CHAIN 1 236 Apoptosis regulator Bcl-2. FT /FTId=PRO_0000289601. FT TRANSMEM 209 230 Potential. FT MOTIF 10 30 BH4. FT MOTIF 90 104 BH3. FT MOTIF 133 152 BH1. FT MOTIF 184 199 BH2. FT SITE 64 65 Cleavage; by caspase-3 and caspase-9. FT MOD_RES 70 70 Phosphoserine; by PKC (By similarity). SQ SEQUENCE 236 AA; 26449 MW; BC22E0CEFD3EB228 CRC64; MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DVGDVDAAPL GAAPTPGIFS FQPESNPTPA VHRDMAARTS PLRPIVATTG PTLSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR HLHTWIQDNG GWDAFVELYG PTMQPLFDFS WLSLKALLSL ALVGACITLG AYLGHK //