(data stored in ACNUC9552 zone)


ID   HS18_PE591                           STANDARD;      PRT;   239 AA.
AC   HS18_PE591; P10415; P10416; Q13842; Q16197;
DT   00-JAN-0000 (Rel. 1, Created)
DT   00-JAN-0000 (Rel. 2, Last sequence update)
DT   00-JAN-0000 (Rel. 3, Last annotation update)
DE   RecName: Full=Apoptosis regulator Bcl-2; (HS18.PE591).
GN   Name=BCL2;
OC   Eukaryota; Metazoa; Eumetazoa; Bilateria; Coelomata; Deuterostomia;
OC   Chordata; Craniata; Vertebrata; Gnathostomata; Teleostomi; Euteleostomi;
OC   Sarcopterygii; Tetrapoda; Amniota; Mammalia; Theria; Eutheria;
OC   Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini;
OC   Hominoidea; Hominidae; Homininae; Homo.
OX   NCBI_TaxID=9606;
RN   [0]
RP   -.;
RG   -.;
RL   -.;
CC   -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS HS18.PE591.
CC       Homo sapiens chromosome 18 GRCh37  sequence 1..78017248 annotated by
CC       Ensembl
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).
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, RAF-1 and TP53BP2. Binding to FKBP8 seems to target BCL2
CC       to the mitochondria and probably interferes with the binding of
CC       BCL2 to its targets. Interacts with BAG1 in an ATP-dependent
CC       manner.
CC       Self; NbExp=3; IntAct=EBI-77694, EBI-77694;
CC       Q92934:BAD; NbExp=4; IntAct=EBI-77694, EBI-700771;
CC       Q61337:Bad (xeno); NbExp=5; IntAct=EBI-77694, EBI-400328;
CC       Q07812:BAX; NbExp=2; IntAct=EBI-77694, EBI-516580;
CC       Q9BXH1:BBC3; NbExp=4; IntAct=EBI-77694, EBI-519884;
CC       P51572:BCAP31; NbExp=2; IntAct=EBI-77694, EBI-77683;
CC       O43521:BCL2L11; NbExp=2; IntAct=EBI-77694, EBI-526406;
CC       O43521-2:BCL2L11; NbExp=3; IntAct=EBI-77694, EBI-526420;
CC       P55957:BID; NbExp=3; IntAct=EBI-77694, EBI-519672;
CC       Q13323:BIK; NbExp=2; IntAct=EBI-77694, EBI-700794;
CC       Q91ZE9:Bmf (xeno); NbExp=2; IntAct=EBI-77694, EBI-708032;
CC       O60238:BNIP3L; NbExp=2; IntAct=EBI-77694, EBI-849893;
CC       Q9C000:NLRP1; NbExp=12; IntAct=EBI-77694, EBI-1220518;
CC       P22736:NR4A1; NbExp=7; IntAct=EBI-77694, EBI-721550;
CC       O15304:SIVA1; NbExp=2; IntAct=EBI-77694, EBI-520756;
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       Event=Alternative splicing; Named isoforms=2;
CC       Name=Alpha;
CC         IsoId=P10415-1; Sequence=Displayed;
CC       Name=Beta;
CC         IsoId=P10415-2; Sequence=VSP_000512;
CC   -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC   -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and
CC       for interaction with RAF-1.
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.
CC       Dephosphorylated by protein phosphatase 2A (PP2A) (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.
CC   -!- PTM: Monoubiquitinated by PARK2, leading to increase its
CC       stability.
CC   -!- DISEASE: Note=A chromosomal aberration involving BCL2 has been
CC       found in chronic lymphatic leukemia. Translocation
CC       t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations
CC       found in non-Hodgkin lymphomas carrying the chromosomal
CC       translocation could be attributed to the Ig somatic hypermutation
CC       mechanism resulting in nucleotide transitions.
CC   -!- SIMILARITY: Belongs to the Bcl-2 family.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/BCL2ID49.html";
CC       URL="http://egp.gs.washington.edu/data/bcl2/";
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Bcl-2 entry;
CC       URL="http://en.wikipedia.org/wiki/Bcl-2";
CC   -!- GENE_FAMILY: HOG000056452 [ FAMILY / ALN / TREE ]
DR   HOGENOM:Homo_sapiens;ENSG00000171791;ENST00000398117;ENSP00000381185.
DR   EMBL; AF401211; - ;
DR   EMBL; AY220759; - ;
DR   EMBL; BC027258; - ;
DR   EMBL; EU287875; - ;
DR   EMBL; M13994; - ;
DR   EMBL; M13995; - ;
DR   EMBL; M14745; - ;
DR   EMBL; S72602; - ;
DR   EMBL; X06487; - ;
DR   UniProtKB/Swiss-Prot; P10415; P10416; Q13842; Q16197; -.
DR   EMBL; M13994; AAA51813.1; ALT_SEQ; mRNA.
DR   EMBL; M13995; AAA51814.1; ALT_SEQ; mRNA.
DR   EMBL; M14745; AAA35591.1; -; mRNA.
DR   EMBL; X06487; CAA29778.1; -; mRNA.
DR   EMBL; AY220759; AAO26045.1; -; Genomic_DNA.
DR   EMBL; BC027258; AAH27258.1; -; mRNA.
DR   EMBL; S72602; AAD14111.1; ALT_SEQ; Genomic_DNA.
DR   IPI; IPI00020961; -.
DR   IPI; IPI00217817; -.
DR   PIR; B29409; TVHUB1.
DR   PIR; C37332; TVHUA1.
DR   RefSeq; NP_000624.2; NM_000633.2.
DR   UniGene; Hs.150749; -.
DR   PDB; 1G5M; NMR; -; A=1-207.
DR   PDB; 1GJH; NMR; -; A=1-207.
DR   PDB; 1YSW; NMR; -; A=3-207.
DR   PDB; 2O21; NMR; -; A=3-207.
DR   PDB; 2O22; NMR; -; A=3-207.
DR   PDB; 2O2F; NMR; -; A=8-204.
DR   PDB; 2W3L; X-ray; 2.10 A; A/B=9-206.
DR   PDB; 2XA0; X-ray; 2.70 A; A/B=1-207.
DR   PDBsum; 1G5M; -.
DR   PDBsum; 1GJH; -.
DR   PDBsum; 1YSW; -.
DR   PDBsum; 2O21; -.
DR   PDBsum; 2O22; -.
DR   PDBsum; 2O2F; -.
DR   PDBsum; 2W3L; -.
DR   PDBsum; 2XA0; -.
DR   ProteinModelPortal; P10415; -.
DR   SMR; P10415; 3-207.
DR   DisProt; DP00297; -.
DR   DIP; DIP-1043N; -.
DR   IntAct; P10415; 34.
DR   MINT; MINT-87089; -.
DR   STRING; P10415; -.
DR   PhosphoSite; P10415; -.
DR   PRIDE; P10415; -.
DR   Ensembl; ENST00000333681; ENSP00000329623; ENSG00000171791.
DR   Ensembl; ENST00000398117; ENSP00000381185; ENSG00000171791.
DR   GeneID; 596; -.
DR   KEGG; hsa:596; -.
DR   UCSC; uc002lit.1; human.
DR   UCSC; uc002liv.1; human.
DR   CTD; 596; -.
DR   GeneCards; GC18M057487; -.
DR   H-InvDB; HIX0014496; -.
DR   HGNC; HGNC:990; BCL2.
DR   HPA; CAB000003; -.
DR   MIM; 151430; gene+phenotype.
DR   neXtProt; NX_P10415; -.
DR   Orphanet; 545; Follicular lymphoma.
DR   eggNOG; prNOG05190; -.
DR   InParanoid; P10415; -.
DR   OrthoDB; EOG4X97J4; -.
DR   PhylomeDB; P10415; -.
DR   Pathway_Interaction_DB; caspase_pathway; Caspase cascade in apoptosis.
DR   Pathway_Interaction_DB; ceramidepathway; Ceramide signaling pathway.
DR   Pathway_Interaction_DB; epopathway; EPO signaling pathway.
DR   Pathway_Interaction_DB; faspathway; FAS signaling pathway (CD95).
DR   Pathway_Interaction_DB; hivnefpathway; HIV-1 Nef: Negative effector of Fas and TNF-alpha.
DR   Pathway_Interaction_DB; il2_pi3kpathway; IL2 signaling events mediated by PI3K.
DR   Pathway_Interaction_DB; il2_stat5pathway; IL2 signaling events mediated by STAT5.
DR   Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events.
DR   Pathway_Interaction_DB; nfat_3pathway; Role of Calcineurin-dependent NFAT signaling in lymphocytes.
DR   Pathway_Interaction_DB; rxr_vdr_pathway; RXR and RAR hetrodimerization with other nuclear receptor.
DR   Pathway_Interaction_DB; kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit).
DR   Reactome; REACT_578; Apoptosis.
DR   Reactome; REACT_6900; Immune System.
DR   DrugBank; DB01248; Docetaxel.
DR   DrugBank; DB01073; Fludarabine.
DR   DrugBank; DB01065; Melatonin.
DR   DrugBank; DB01229; Paclitaxel.
DR   DrugBank; DB01367; Rasagiline.
DR   NextBio; 2423; -.
DR   PMAP-CutDB; P10415; -.
DR   ArrayExpress; P10415; -.
DR   Bgee; P10415; -.
DR   CleanEx; HS_BCL2; -.
DR   Genevestigator; P10415; -.
DR   GermOnline; ENSG00000171791; Homo sapiens.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR   GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR   GO; GO:0046930; C:pore complex; IDA:BHF-UCL.
DR   GO; GO:0051434; F:BH3 domain binding; IPI:UniProtKB.
DR   GO; GO:0015267; F:channel activity; IDA:BHF-UCL.
DR   GO; GO:0002020; F:protease binding; IDA:UniProtKB.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR   GO; GO:0008633; P:activation of pro-apoptotic gene products; EXP:Reactome.
DR   GO; GO:0006916; P:anti-apoptosis; IDA:UniProtKB.
DR   GO; GO:0070059; P:apoptosis in response to endoplasmic reticulum stress; IDA:MGI.
DR   GO; GO:0042100; P:B cell proliferation; IDA:MGI.
DR   GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0007565; P:female pregnancy; NAS:UniProtKB.
DR   GO; GO:0006959; P:humoral immune response; TAS:UniProtKB.
DR   GO; GO:0008629; P:induction of apoptosis by intracellular signals; TAS:Reactome.
DR   GO; GO:0032848; P:negative regulation of cellular pH reduction; IDA:UniProtKB.
DR   GO; GO:0051902; P:negative regulation of mitochondrial depolarization; TAS:UniProtKB.
DR   GO; GO:0043524; P:negative regulation of neuron apoptosis; IDA:MGI.
DR   GO; GO:0051402; P:neuron apoptosis; TAS:HGNC.
DR   GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB.
DR   GO; GO:0030307; P:positive regulation of cell growth; IDA:MGI.
DR   GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
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:0043497; P:regulation of protein heterodimerization activity; IDA:UniProtKB.
DR   GO; GO:0043496; P:regulation of protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0022898; P:regulation of transmembrane transporter activity; IDA:BHF-UCL.
DR   GO; GO:0001836; P:release of cytochrome c from mitochondria; NAS:UniProtKB.
DR   GO; GO:0034097; P:response to cytokine stimulus; IDA:MGI.
DR   GO; GO:0006974; P:response to DNA damage stimulus; IMP:UniProtKB.
DR   GO; GO:0042493; P:response to drug; IMP:UniProtKB.
DR   GO; GO:0010039; P:response to iron ion; IDA:UniProtKB.
DR   GO; GO:0035094; P:response to nicotine; IDA:UniProtKB.
DR   GO; GO:0009636; P:response to toxin; IDA:MGI.
DR   InterPro; IPR013278; Apop_reg_Bcl2.
DR   InterPro; IPR002475; Bcl2-like_apoptosis.
DR   InterPro; IPR000712; Bcl2_BH.
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; IPR004725; Bcl2_reg.
DR   Pfam; PF00452; Bcl-2; 1.
DR   Pfam; PF02180; BH4; 1.
DR   SMART; SM00337; BCL; 1.
DR   SMART; SM00265; BH4; 1.
DR   TIGRFAMs; TIGR00865; Bcl-2; 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   ENSG000001717911755old_1320000031; ENSP000003811857901old_1320000031;
KW   A9QXG9_HUMAN; Q96PA0_HUMAN; AF401211; AY220759; BC027258; EU287875;
KW   M13995; M14745; S72602; X06487;
KW   3D-structure; Alternative splicing; Apoptosis;
KW   Chromosomal rearrangement; Complete proteome; Disease mutation;
KW   Endoplasmic reticulum; Membrane; Mitochondrion;
KW   Mitochondrion outer membrane; Nucleus; Phosphoprotein; Polymorphism;
KW   Proto-oncogene; Reference proteome; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.

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