ID BCL2_CANLF Reviewed; 236 AA. AC Q6R755; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 08-MAY-2019, entry version 72. DE RecName: Full=Apoptosis regulator Bcl-2; GN Name=BCL2; OS Canis lupus familiaris (Dog) (Canis familiaris). 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). May CC attenuate inflammation by impairing NLRP1-inflammasome activation, CC hence CASP1 activation and IL1B release (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:P10415}. 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 (By CC similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, CC MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the CC mitochondria and probably interferes with the binding of BCL2 to CC its targets. Interacts with BAG1 in an ATP-dependent manner. CC Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated CC form). Interacts (via the BH4 domain) with EGLN3; the interaction CC prevents the formation of the BAX-BCL2 complex and inhibits the CC anti-apoptotic activity of BCL2 (By similarity). Interacts with CC G0S2; this interaction also prevents the formation of the anti- CC apoptotic BAX-BCL2 complex (By similarity). Interacts with BOP (By CC similarity). Interacts with the SCF(FBXO10) complex (By CC similarity). Interacts (via the loop between motifs BH4 and BH3) CC with NLRP1 (via LRR repeats) (By similarity). Interacts with CC GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:P10415, CC ECO:0000250|UniProtKB:P10417}. CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250}; CC Single-pass membrane protein {ECO:0000250}. Nucleus membrane CC {ECO:0000250}; Single-pass membrane protein {ECO:0000250}. CC Endoplasmic reticulum membrane {ECO:0000250}; Single-pass membrane CC protein {ECO:0000250}. CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and CC for interaction with RAF1 and EGLN3. {ECO:0000250}. CC -!- DOMAIN: BH1 and BH2 domains are required for the interaction with CC BAX and for anti-apoptotic activity. CC {ECO:0000250|UniProtKB:P10415}. CC -!- DOMAIN: The loop between motifs BH4 and BH3 is required for the CC interaction with NLRP1. {ECO:0000250|UniProtKB:P10415}. 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). Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 CC and Ser-84, wich stimulates starvation-induced autophagy (By CC similarity). Dephosphorylated by protein phosphatase 2A (PP2A) (By CC similarity). {ECO:0000250}. 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). {ECO:0000250}. CC -!- PTM: Monoubiquitinated by PRKN, leading to increase its stability. CC Ubiquitinated by SCF(FBXO10), leading to its degradation by the CC proteasome. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}. 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 InParanoid; Q6R755; -. DR Proteomes; UP000002254; Unplaced. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0046982; F:protein heterodimerization activity; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central. DR Gene3D; 1.10.437.10; -; 1. DR InterPro; IPR013278; Apop_reg_Bcl2. DR InterPro; IPR002475; Bcl2-like. DR InterPro; IPR004725; Bcl2/BclX. DR InterPro; IPR020717; Bcl2_BH1_motif_CS. DR InterPro; IPR020726; Bcl2_BH2_motif_CS. DR InterPro; IPR020728; Bcl2_BH3_motif_CS. DR InterPro; IPR003093; Bcl2_BH4. DR InterPro; IPR020731; Bcl2_BH4_motif_CS. DR InterPro; IPR036834; Blc2-like_sf. DR InterPro; IPR026298; Blc2_fam. DR PANTHER; PTHR11256; PTHR11256; 1. DR PANTHER; PTHR11256:SF11; PTHR11256:SF11; 1. DR Pfam; PF00452; Bcl-2; 1. DR Pfam; PF02180; BH4; 1. DR PRINTS; PR01863; APOPREGBCL2. DR PRINTS; PR01862; BCL2FAMILY. DR SMART; SM00265; BH4; 1. DR SUPFAM; SSF56854; SSF56854; 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; Complete proteome; Endoplasmic reticulum; Membrane; KW Mitochondrion; Mitochondrion outer membrane; Nucleus; Phosphoprotein; KW Reference proteome; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN 1 236 Apoptosis regulator Bcl-2. FT /FTId=PRO_0000289601. FT TRANSMEM 209 230 Helical. {ECO:0000255}. 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 69 69 Phosphothreonine; by MAPK8. FT {ECO:0000250|UniProtKB:P10415}. FT MOD_RES 70 70 Phosphoserine; by MAPK8 and PKC. FT {ECO:0000250|UniProtKB:P10415}. FT MOD_RES 84 84 Phosphoserine; by MAPK8. FT {ECO:0000250|UniProtKB:P10415}. 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 //