BCL2_BOVIN
ID BCL2_BOVIN Reviewed; 229 AA.
AC O02718;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Apoptosis regulator Bcl-2;
GN Name=BCL2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Thymus;
RX PubMed=9501056; DOI=10.1006/viro.1998.9029;
RA Reyes R.A., Cockerell G.L.;
RT "Increased ratio of bcl-2/bax expression is associated with bovine leukemia
RT virus-induced leukemogenesis in cattle.";
RL Virology 242:184-192(1998).
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 BH3 motif is required for XIAP-mediated ubiquitination and
CC subsequent induction of apoptosis. {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-63 regulates anti-
CC apoptotic activity. Growth factor-stimulated phosphorylation on Ser-63
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. Phosphorylated by
CC MAPK8/JNK1 at Thr-62, Ser-63 and Ser-77, wich stimulates starvation-
CC induced autophagy (By similarity). Dephosphorylated by protein
CC phosphatase 2A (PP2A) (By similarity). {ECO:0000250|UniProtKB:P10415,
CC 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 (By similarity). {ECO:0000250|UniProtKB:P10415}.
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; U92434; AAB53319.1; -; mRNA.
DR AlphaFoldDB; O02718; -.
DR SMR; O02718; -.
DR STRING; 9913.ENSBTAP00000025701; -.
DR PaxDb; O02718; -.
DR PRIDE; O02718; -.
DR eggNOG; KOG4728; Eukaryota.
DR InParanoid; O02718; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:HGNC.
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; ISS:HGNC.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0032848; P:negative regulation of cellular pH reduction; ISS:HGNC.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:HGNC-UCL.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISS:HGNC-UCL.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:HGNC-UCL.
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 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Endoplasmic reticulum; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..229
FT /note="Apoptosis regulator Bcl-2"
FT /id="PRO_0000143046"
FT TRANSMEM 202..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 30..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 10..30
FT /note="BH4"
FT MOTIF 83..97
FT /note="BH3"
FT MOTIF 126..145
FT /note="BH1"
FT MOTIF 177..192
FT /note="BH2"
FT COMPBIAS 58..81
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 34..35
FT /note="Cleavage; by caspases"
FT /evidence="ECO:0000250"
FT MOD_RES 62
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT MOD_RES 63
FT /note="Phosphoserine; by MAPK8 and PKC"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT MOD_RES 77
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
SQ SEQUENCE 229 AA; 25100 MW; AD1DD0AF98FFF11D CRC64;
MAHAGGTGYD NREIVMKYIH YKLSQRGYEW DAGDAGAAPP GAAPAPGILS SQPGRTPAPS
RTSPPPPPAA AAGPAPSPVP PVVHLTLRQA GDDFSRRYRR DFAEMSSQLH LTPFTARERF
ATVVEELFRD GVNWGRIVAF FEFGGVMCVE SVNREMSPLV DSIALWMTEY LNRHLHTWIQ
DNGGWDAFVE LYGPSMRPLF DFSWLSLKAL LSLALVGACI TLGAYLGHK
