(data stored in ACNUC9552 zone)

SWISSPROT: BCL2_RAT

ID   BCL2_RAT                Reviewed;         236 AA.
AC   P49950; Q62837; Q64032;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   30-AUG-2017, entry version 139.
DE   RecName: Full=Apoptosis regulator Bcl-2;
GN   Name=Bcl2; Synonyms=Bcl-2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=8144041; DOI=10.1016/0378-1119(94)90561-4;
RA   Sato T., Irie S., Krajewski S., Reed J.C.;
RT   "Cloning and sequencing of a cDNA encoding the rat Bcl-2 protein.";
RL   Gene 140:291-292(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Ovary;
RX   PubMed=7828536; DOI=10.1210/endo.136.1.7828536;
RA   Tilly J.L., Tilly K.I., Kenton M.L., Johnson A.L.;
RT   "Expression of members of the Bcl-2 gene family in the immature rat
RT   ovary: equine chorionic gonadotropin-mediated inhibition of granulosa
RT   cell apoptosis is associated with decreased Bax and constitutive Bcl-2
RT   and Bcl-xlong messenger ribonucleic acid levels.";
RL   Endocrinology 136:232-241(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 19-172.
RX   PubMed=7969891; DOI=10.1016/0306-4522(94)90069-8;
RA   Castren E., Ohga Y., Berzaghi M.P., Tzimagiorgis G., Thoenen H.,
RA   Lindholm D.;
RT   "bcl-2 messenger RNA is localized in neurons of the developing and
RT   adult rat brain.";
RL   Neuroscience 61:165-177(1994).
RN   [4]
RP   INTERACTION WITH PPIF.
RX   PubMed=19228691; DOI=10.1074/jbc.M808750200;
RA   Eliseev R.A., Malecki J., Lester T., Zhang Y., Humphrey J.,
RA   Gunter T.E.;
RT   "Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic
RT   effect.";
RL   J. Biol. Chem. 284:9692-9699(2009).
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). May attenuate
CC       inflammation by impairing NLRP1-inflammasome activation, hence
CC       CASP1 activation and IL1B release (By similarity).
CC       {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. Also
CC       interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, FKBP8, MRPL41,
CC       and TP53BP2. 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). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P10415}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass
CC       membrane protein. Nucleus membrane; Single-pass membrane protein.
CC       Endoplasmic reticulum membrane; Single-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed in a variety of tissues, with
CC       highest levels in reproductive tissues. In the adult brain,
CC       expression is localized in mitral cells of the olfactory bulb,
CC       granule and pyramidal neurons of hippocampus, pontine nuclei,
CC       cerebellar granule neurons, and in ependymal cells. In prenatal
CC       brain, expression is higher and localized in the neuroepithelium
CC       and in the cortical plate.
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. 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
CC       by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, wich stimulates
CC       starvation-induced autophagy (By similarity). Dephosphorylated by
CC       protein phosphatase 2A (PP2A) (By 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}.
DR   EMBL; L14680; AAA53662.1; -; mRNA.
DR   EMBL; U34964; AAA77687.1; -; mRNA.
DR   EMBL; S74122; -; NOT_ANNOTATED_CDS; mRNA.
DR   PIR; I53744; I53744.
DR   PIR; I67432; I67432.
DR   RefSeq; NP_058689.1; NM_016993.1.
DR   UniGene; Rn.9996; -.
DR   ProteinModelPortal; P49950; -.
DR   SMR; P49950; -.
DR   BioGrid; 246412; 1.
DR   DIP; DIP-30849N; -.
DR   IntAct; P49950; 2.
DR   STRING; 10116.ENSRNOP00000003768; -.
DR   iPTMnet; P49950; -.
DR   PhosphoSitePlus; P49950; -.
DR   PaxDb; P49950; -.
DR   GeneID; 24224; -.
DR   KEGG; rno:24224; -.
DR   UCSC; RGD:2199; rat.
DR   CTD; 596; -.
DR   RGD; 2199; Bcl2.
DR   eggNOG; KOG4728; Eukaryota.
DR   eggNOG; ENOG41123S0; LUCA.
DR   HOGENOM; HOG000056452; -.
DR   HOVERGEN; HBG004472; -.
DR   InParanoid; P49950; -.
DR   KO; K02161; -.
DR   PhylomeDB; P49950; -.
DR   PRO; PR:P49950; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005829; C:cytosol; IDA:RGD.
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:0005739; C:mitochondrion; IDA:RGD.
DR   GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0051400; F:BH domain binding; IPI:RGD.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:RGD.
DR   GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR   GO; GO:0007568; P:aging; IEP:RGD.
DR   GO; GO:0006915; P:apoptotic process; IEP:RGD.
DR   GO; GO:0007420; P:brain development; IEP:RGD.
DR   GO; GO:1902618; P:cellular response to fluoride; IEP:RGD.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR   GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR   GO; GO:0034349; P:glial cell apoptotic process; IEP:RGD.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR   GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR   GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
DR   GO; GO:0001541; P:ovarian follicle development; IEP:RGD.
DR   GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:HGNC.
DR   GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISS:HGNC.
DR   GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:HGNC.
DR   GO; GO:0010044; P:response to aluminum ion; IEP:RGD.
DR   GO; GO:1904645; P:response to amyloid-beta; IEP:RGD.
DR   GO; GO:0031000; P:response to caffeine; IEP:RGD.
DR   GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR   GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR   GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR   GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR   GO; GO:0042493; P:response to drug; IEP:RGD.
DR   GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR   GO; GO:0036017; P:response to erythropoietin; IEP:RGD.
DR   GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR   GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR   GO; GO:0051593; P:response to folic acid; IEP:RGD.
DR   GO; GO:0009408; P:response to heat; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR   GO; GO:0032868; P:response to insulin; IEP:RGD.
DR   GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR   GO; GO:0034284; P:response to monosaccharide; IEP:RGD.
DR   GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR   GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0080184; P:response to phenylpropanoid; IEP:RGD.
DR   GO; GO:0033197; P:response to vitamin E; IEP:RGD.
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; IPR026298; Blc2_fam.
DR   PANTHER; PTHR11256; PTHR11256; 1.
DR   PANTHER; PTHR11256:SF55; PTHR11256:SF55; 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   1: Evidence at protein level;
DR   PRODOM; P49950.
DR   SWISS-2DPAGE; P49950.
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_0000143050.
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         34     35       Cleavage; by caspases. {ECO:0000250}.
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}.
FT   CONFLICT     42     42       A -> R (in Ref. 2; AAA77687).
FT                                {ECO:0000305}.
FT   CONFLICT    157    157       E -> G (in Ref. 1; AAA53662).
FT                                {ECO:0000305}.
FT   CONFLICT    164    164       S -> Y (in Ref. 2; AAA77687).
FT                                {ECO:0000305}.
FT   CONFLICT    212    212       L -> Q (in Ref. 2; AAA77687).
FT                                {ECO:0000305}.
SQ   SEQUENCE   236 AA;  26622 MW;  E7688CB9071A872A CRC64;
     MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DTGDEDSAPL RAAPTPGIFS FQPESNRTPA
     VHRDTAARTS PLRPLVANAG PALSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP
     FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR
     HLHTWIQDNG GWDAFVELYG PSMRPLFDFS WLSLKTLLSL ALVGACITLG AYLGHK
//

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