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Protein

Apoptosis regulator Bcl-2

Gene

Bcl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-MMU-111447 Activation of BAD and translocation to mitochondria
R-MMU-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-MMU-844455 The NLRP1 inflammasome

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulator Bcl-2
Gene namesi
Name:Bcl2
Synonyms:Bcl-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:88138 Bcl2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei209 – 230HelicalSequence analysisAdd BLAST22

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

In response to intraperitoneal injection of muramyl dipeptide (MDP), knockout animals show lower serum IL1B levels than wild type. Mutant macrophages release 30% less IL1B than the wild-type cells.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70S → A: Loss of phosphorylation. Unable to suppress apoptosis. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3309111

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430491 – 236Apoptosis regulator Bcl-2Add BLAST236

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei69Phosphothreonine; by MAPK8By similarity1
Modified residuei70Phosphoserine; by MAPK8 and PKC1 Publication1
Modified residuei84Phosphoserine; by MAPK8By similarity1

Post-translational modificationi

Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, wich stimulates starvation-induced autophagy (By similarity). Dephosphorylated by protein phosphatase 2A (PP2A).By similarity1 Publication
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.
Monoubiquitinated by PRKN, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei34 – 35Cleavage; by caspasesBy similarity2

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP10417
PeptideAtlasiP10417
PRIDEiP10417

PTM databases

iPTMnetiP10417
PhosphoSitePlusiP10417

Expressioni

Tissue specificityi

Expressed in a variety of tissues.

Gene expression databases

BgeeiENSMUSG00000057329 Expressed in 258 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_BCL2
ExpressionAtlasiP10417 baseline and differential
GenevisibleiP10417 MM

Interactioni

Subunit structurei

Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2 (By similarity). Interacts with EI24. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with PPIF; the interaction is impaired by CsA (By similarity). Interacts with BOP (By similarity). Interacts with the SCF(FBXO10) complex (By similarity). Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats) (By similarity).By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198318, 32 interactors
ComplexPortaliCPX-2017 BCL-2 dimer
CPX-2019 BAD:BCL-2 complex
CPX-2024 BID:BCL-2 complex
CPX-2027 PUMA:BCL-2 complex
CPX-2036 BIM:BCL-2 complex
CORUMiP10417
DIPiDIP-1065N
IntActiP10417, 10 interactors
MINTiP10417
STRINGi10090.ENSMUSP00000108371

Chemistry databases

BindingDBiP10417

Structurei

3D structure databases

ProteinModelPortaliP10417
SMRiP10417
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi10 – 30BH4Add BLAST21
Motifi90 – 104BH3Add BLAST15
Motifi133 – 152BH1Add BLAST20
Motifi184 – 199BH2Add BLAST16

Domaini

The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.By similarity
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.By similarity

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4728 Eukaryota
ENOG41123S0 LUCA
GeneTreeiENSGT00530000062935
HOGENOMiHOG000056452
HOVERGENiHBG004472
InParanoidiP10417
KOiK02161
OMAiEWDAGDA
OrthoDBiEOG091G0OCU
TreeFamiTF315834

Family and domain databases

Gene3Di1.10.437.10, 1 hit
InterProiView protein in InterPro
IPR013278 Apop_reg_Bcl2
IPR002475 Bcl2-like
IPR004725 Bcl2/BclX
IPR020717 Bcl2_BH1_motif_CS
IPR020726 Bcl2_BH2_motif_CS
IPR020728 Bcl2_BH3_motif_CS
IPR003093 Bcl2_BH4
IPR020731 Bcl2_BH4_motif_CS
IPR036834 Blc2-like_sf
IPR026298 Blc2_fam
PANTHERiPTHR11256 PTHR11256, 1 hit
PTHR11256:SF11 PTHR11256:SF11, 1 hit
PfamiView protein in Pfam
PF00452 Bcl-2, 1 hit
PF02180 BH4, 1 hit
PRINTSiPR01863 APOPREGBCL2
PR01862 BCL2FAMILY
SMARTiView protein in SMART
SM00265 BH4, 1 hit
SUPFAMiSSF56854 SSF56854, 1 hit
TIGRFAMsiTIGR00865 bcl-2, 1 hit
PROSITEiView protein in PROSITE
PS50062 BCL2_FAMILY, 1 hit
PS01080 BH1, 1 hit
PS01258 BH2, 1 hit
PS01259 BH3, 1 hit
PS01260 BH4_1, 1 hit
PS50063 BH4_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform Alpha (identifier: P10417-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDADAAPL GAAPTPGIFS
60 70 80 90 100
FQPESNPMPA VHRDMAARTS PLRPLVATAG PALSPVPPVV HLTLRRAGDD
110 120 130 140 150
FSRRYRRDFA EMSSQLHLTP FTARGRFATV VEELFRDGVN WGRIVAFFEF
160 170 180 190 200
GGVMCVESVN REMSPLVDNI ALWMTEYLNR HLHTWIQDNG GWDAFVELYG
210 220 230
PSMRPLFDFS WLSLKTLLSL ALVGACITLG AYLGHK
Length:236
Mass (Da):26,407
Last modified:October 3, 2012 - v3
Checksum:i80FDCFE78C735092
GO
Isoform Beta (identifier: P10417-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-236: DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK → VGACLVE

Show »
Length:199
Mass (Da):22,281
Checksum:iF13C8037262BA955
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti64D → E in AAA37281 (PubMed:3032455).Curated1
Sequence conflicti64D → E in AAA37282 (PubMed:3032455).Curated1
Sequence conflicti89V → C in AAA37281 (PubMed:3032455).Curated1
Sequence conflicti89V → C in AAA37282 (PubMed:3032455).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000513193 – 236DAFVE…YLGHK → VGACLVE in isoform Beta. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L31532, M16506 Genomic DNA Translation: AAA37282.1
M16506 Genomic DNA Translation: AAA37281.1
AC122842 Genomic DNA No translation available.
AC162916 Genomic DNA No translation available.
CH466520 Genomic DNA Translation: EDL39862.1
BC095964 mRNA Translation: AAH95964.1
CCDSiCCDS15209.1 [P10417-1]
CCDS78667.1 [P10417-2]
PIRiA25960 TVMSA1
B25960 TVMSB1
RefSeqiNP_033871.2, NM_009741.5 [P10417-1]
UniGeneiMm.257460

Genome annotation databases

EnsembliENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329 [P10417-1]
ENSMUST00000189999; ENSMUSP00000139856; ENSMUSG00000057329 [P10417-2]
GeneIDi12043
KEGGimmu:12043
UCSCiuc007cgw.2 mouse [P10417-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L31532, M16506 Genomic DNA Translation: AAA37282.1
M16506 Genomic DNA Translation: AAA37281.1
AC122842 Genomic DNA No translation available.
AC162916 Genomic DNA No translation available.
CH466520 Genomic DNA Translation: EDL39862.1
BC095964 mRNA Translation: AAH95964.1
CCDSiCCDS15209.1 [P10417-1]
CCDS78667.1 [P10417-2]
PIRiA25960 TVMSA1
B25960 TVMSB1
RefSeqiNP_033871.2, NM_009741.5 [P10417-1]
UniGeneiMm.257460

3D structure databases

ProteinModelPortaliP10417
SMRiP10417
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198318, 32 interactors
ComplexPortaliCPX-2017 BCL-2 dimer
CPX-2019 BAD:BCL-2 complex
CPX-2024 BID:BCL-2 complex
CPX-2027 PUMA:BCL-2 complex
CPX-2036 BIM:BCL-2 complex
CORUMiP10417
DIPiDIP-1065N
IntActiP10417, 10 interactors
MINTiP10417
STRINGi10090.ENSMUSP00000108371

Chemistry databases

BindingDBiP10417
ChEMBLiCHEMBL3309111

PTM databases

iPTMnetiP10417
PhosphoSitePlusiP10417

Proteomic databases

PaxDbiP10417
PeptideAtlasiP10417
PRIDEiP10417

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329 [P10417-1]
ENSMUST00000189999; ENSMUSP00000139856; ENSMUSG00000057329 [P10417-2]
GeneIDi12043
KEGGimmu:12043
UCSCiuc007cgw.2 mouse [P10417-1]

Organism-specific databases

CTDi596
MGIiMGI:88138 Bcl2

Phylogenomic databases

eggNOGiKOG4728 Eukaryota
ENOG41123S0 LUCA
GeneTreeiENSGT00530000062935
HOGENOMiHOG000056452
HOVERGENiHBG004472
InParanoidiP10417
KOiK02161
OMAiEWDAGDA
OrthoDBiEOG091G0OCU
TreeFamiTF315834

Enzyme and pathway databases

ReactomeiR-MMU-111447 Activation of BAD and translocation to mitochondria
R-MMU-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
R-MMU-844455 The NLRP1 inflammasome

Miscellaneous databases

ChiTaRSiBcl2 mouse
PROiPR:P10417
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000057329 Expressed in 258 organ(s), highest expression level in mesenteric lymph node
CleanExiMM_BCL2
ExpressionAtlasiP10417 baseline and differential
GenevisibleiP10417 MM

Family and domain databases

Gene3Di1.10.437.10, 1 hit
InterProiView protein in InterPro
IPR013278 Apop_reg_Bcl2
IPR002475 Bcl2-like
IPR004725 Bcl2/BclX
IPR020717 Bcl2_BH1_motif_CS
IPR020726 Bcl2_BH2_motif_CS
IPR020728 Bcl2_BH3_motif_CS
IPR003093 Bcl2_BH4
IPR020731 Bcl2_BH4_motif_CS
IPR036834 Blc2-like_sf
IPR026298 Blc2_fam
PANTHERiPTHR11256 PTHR11256, 1 hit
PTHR11256:SF11 PTHR11256:SF11, 1 hit
PfamiView protein in Pfam
PF00452 Bcl-2, 1 hit
PF02180 BH4, 1 hit
PRINTSiPR01863 APOPREGBCL2
PR01862 BCL2FAMILY
SMARTiView protein in SMART
SM00265 BH4, 1 hit
SUPFAMiSSF56854 SSF56854, 1 hit
TIGRFAMsiTIGR00865 bcl-2, 1 hit
PROSITEiView protein in PROSITE
PS50062 BCL2_FAMILY, 1 hit
PS01080 BH1, 1 hit
PS01258 BH2, 1 hit
PS01259 BH3, 1 hit
PS01260 BH4_1, 1 hit
PS50063 BH4_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBCL2_MOUSE
AccessioniPrimary (citable) accession number: P10417
Secondary accession number(s): P10418, Q4VBF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 3, 2012
Last modified: October 10, 2018
This is version 194 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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