BCL2_CRIGR
ID BCL2_CRIGR Reviewed; 236 AA.
AC Q9JJV8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Apoptosis regulator Bcl-2;
GN Name=BCL2;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=10973819; DOI=10.1006/bbrc.2000.3386;
RA Tomicic M.T., Christmann M., Kaina B.;
RT "Cloning and functional analysis of cDNA encoding the hamster Bcl-2
RT protein.";
RL Biochem. Biophys. Res. Commun. 275:899-903(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CLEAVAGE BY CASPASES.
RX PubMed=11181062; DOI=10.1006/bbrc.2001.4367;
RA Tomicic M.T., Kaina B.;
RT "Hamster Bcl-2 protein is cleaved in vitro and in cells by caspase-9 and
RT caspase-3.";
RL Biochem. Biophys. Res. Commun. 281:404-408(2001).
CC -!- FUNCTION: Suppresses apoptosis in a variety of cell systems including
CC factor-dependent lymphohematopoietic and neural cells. Regulates cell
CC death by controlling the mitochondrial membrane permeability. Appears
CC to function in a feedback loop system with caspases. Inhibits caspase
CC activity either by preventing the release of cytochrome c from the
CC mitochondria and/or by binding to the apoptosis-activating factor
CC (APAF-1). Also acts as an inhibitor of autophagy: interacts with BECN1
CC and AMBRA1 during non-starvation conditions and inhibits their
CC autophagy function. May attenuate inflammation by impairing NLRP1-
CC inflammasome activation, hence CASP1 activation and IL1B release.
CC {ECO:0000250|UniProtKB:P10415}.
CC -!- SUBUNIT: Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-
CC X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs,
CC and is necessary for anti-apoptotic activity (By similarity). Interacts
CC with EI24 (By similarity). Also interacts with APAF1, BBC3, BCL2L1,
CC BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the
CC mitochondria and probably interferes with the binding of BCL2 to its
CC targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with
CC RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via
CC the BH4 domain) with EGLN3; the interaction prevents the formation of
CC the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2.
CC Interacts with G0S2; this interaction also prevents the formation of
CC the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP.
CC Interacts with the SCF(FBXO10) complex. Interacts (via the loop between
CC motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2,
CC NLRP3, NLRP4, PYCARD, nor MEFV (By similarity). Interacts with
CC GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity). Interacts
CC with BCAP31. Interacts with IRF3; the interaction is inhibited by
CC Sendai virus infection. Interacts with BECN1; thereby inhibiting
CC autophagy in non-starvation conditions. Interacts with AMBRA1; thereby
CC inhibiting autophagy (By similarity). {ECO:0000250|UniProtKB:P10415,
CC ECO:0000250|UniProtKB:P10417}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P10415}; Single-pass membrane protein
CC {ECO:0000255}. Nucleus membrane {ECO:0000250|UniProtKB:P10415}; Single-
CC pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P10415}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:P10417}.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and for
CC interaction with RAF1 and EGLN3. {ECO:0000250}.
CC -!- DOMAIN: BH1 and BH2 domains are required for the interaction with BAX
CC and for anti-apoptotic activity. {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 -!- DOMAIN: The BH3 motif is required for XIAP-mediated ubiquitination and
CC subsequent induction of apoptosis. {ECO:0000250|UniProtKB:P10415}.
CC -!- PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti-
CC apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70
CC by PKC is required for the anti-apoptosis activity and occurs during
CC the G2/M phase of the cell cycle (By similarity). In the absence of
CC growth factors, BCL2 appears to be phosphorylated by other protein
CC kinases such as ERKs and stress-activated kinases (By similarity).
CC Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, wich
CC stimulates starvation-induced autophagy (By similarity).
CC Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).
CC {ECO:0000250|UniProtKB:P10415, ECO:0000250|UniProtKB:P10417}.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleaved
CC protein, lacking the BH4 motif, has pro-apoptotic activity, causes the
CC release of cytochrome c into the cytosol promoting further caspase
CC activity. {ECO:0000269|PubMed:11181062}.
CC -!- PTM: Monoubiquitinated by PRKN, leading to an increase in its
CC stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by
CC the proteasome. {ECO:0000250|UniProtKB:P10415}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AJ271720; CAB92245.1; -; mRNA.
DR PIR; JC7383; JC7383.
DR AlphaFoldDB; Q9JJV8; -.
DR SMR; Q9JJV8; -.
DR IntAct; Q9JJV8; 1.
DR STRING; 10029.XP_007611354.1; -.
DR Ensembl; ENSCGRT00001031574; ENSCGRP00001027327; ENSCGRG00001024362.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244953; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0046930; C:pore complex; IEA:Ensembl.
DR GO; GO:0051434; F:BH3 domain binding; IEA:Ensembl.
DR GO; GO:0015267; F:channel activity; IEA:Ensembl.
DR GO; GO:0016248; F:channel inhibitor activity; IEA:Ensembl.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0002326; P:B cell lineage commitment; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0060402; P:calcium ion transport into cytosol; IEA:Ensembl.
DR GO; GO:0043375; P:CD8-positive, alpha-beta T cell lineage commitment; IEA:Ensembl.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0021747; P:cochlear nucleus development; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0097048; P:dendritic cell apoptotic process; IEA:Ensembl.
DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0043583; P:ear development; IEA:Ensembl.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0022612; P:gland morphogenesis; IEA:Ensembl.
DR GO; GO:0032835; P:glomerulus development; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0006582; P:melanin metabolic process; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0014031; P:mesenchymal cell development; IEA:Ensembl.
DR GO; GO:0001656; P:metanephros development; IEA:Ensembl.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:2000811; P:negative regulation of anoikis; IEA:Ensembl.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl.
DR GO; GO:0032848; P:negative regulation of cellular pH reduction; IEA:Ensembl.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IEA:Ensembl.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0046671; P:negative regulation of retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0042551; P:neuron maturation; IEA:Ensembl.
DR GO; GO:0048599; P:oocyte development; IEA:Ensembl.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0048753; P:pigment granule organization; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0014042; P:positive regulation of neuron maturation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0048743; P:positive regulation of skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010559; P:regulation of glycoprotein biosynthetic process; IEA:Ensembl.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:0006808; P:regulation of nitrogen utilization; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0045069; P:regulation of viral genome replication; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0003014; P:renal system process; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1904373; P:response to kainic acid; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0046666; P:retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013278; Apop_reg_Bcl2.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
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 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; SM00337; BCL; 1.
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 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Endoplasmic reticulum; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..236
FT /note="Apoptosis regulator Bcl-2"
FT /id="PRO_0000143047"
FT TRANSMEM 209..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 10..30
FT /note="BH4"
FT MOTIF 90..104
FT /note="BH3"
FT MOTIF 133..152
FT /note="BH1"
FT MOTIF 184..199
FT /note="BH2"
FT SITE 64..65
FT /note="Cleavage; by caspase-3 and caspase-9"
FT MOD_RES 69
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT MOD_RES 70
FT /note="Phosphoserine; by MAPK8 and PKC"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT MOD_RES 84
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
SQ SEQUENCE 236 AA; 26491 MW; BECADF1EF3337228 CRC64;
MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DVGDVDAAPL GAAPTPGIFS FQPESNPTPA
VHRDMAARTS PLRPIVATTG PTLSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP
FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR
HLHTWIQDNG GWDAFVELYG PSVRPLFDFS WLSLKTLLSL ALVGACITLG TYLGHK
