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 12-JUN-2007, entry version 18. DE 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; mitochondrial outer membrane; CC single-pass membrane protein (By similarity). Nucleus; nuclear CC membrane; single-pass membrane protein (By similarity). CC Endoplasmic reticulum; endoplasmic reticulum membrane; single-pass CC 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 InterPro; IPR013278; Apop_reg_Bcl2. DR InterPro; IPR012238; Bcl2_apop_reg. 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 PIRSF; PIRSF500115; Bcl2_antiapop; 1. DR PIRSF; PIRSF001714; Bcl2_apop_reg; 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. KW Apoptosis; Endoplasmic reticulum; Membrane; Mitochondrion; KW Nuclear protein; Phosphorylation; 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 //