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Protein

Apoptosis regulator Bcl-2

Gene

Bcl2

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

GO - Molecular functioni

  • BH domain binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: GO_Central

GO - Biological processi

  • aging Source: RGD
  • apoptotic process Source: RGD
  • brain development Source: RGD
  • cellular response to fluoride Source: RGD
  • cellular response to glucose stimulus Source: RGD
  • cellular response to hypoxia Source: RGD
  • cellular response to organic cyclic compound Source: RGD
  • cerebral cortex development Source: RGD
  • extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
  • glial cell apoptotic process Source: RGD
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
  • liver regeneration Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
  • negative regulation of intrinsic apoptotic signaling pathway Source: GO_Central
  • oligodendrocyte differentiation Source: RGD
  • ovarian follicle development Source: RGD
  • regulation of mitochondrial membrane permeability Source: HGNC
  • regulation of mitochondrial membrane potential Source: HGNC
  • release of cytochrome c from mitochondria Source: HGNC
  • response to aluminum ion Source: RGD
  • response to amyloid-beta Source: RGD
  • response to caffeine Source: RGD
  • response to cAMP Source: RGD
  • response to copper ion Source: RGD
  • response to corticosterone Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to electrical stimulus Source: RGD
  • response to erythropoietin Source: RGD
  • response to estrogen Source: RGD
  • response to ethanol Source: RGD
  • response to folic acid Source: RGD
  • response to heat Source: RGD
  • response to hypoxia Source: RGD
  • response to inorganic substance Source: RGD
  • response to insulin Source: RGD
  • response to L-ascorbic acid Source: RGD
  • response to monosaccharide Source: RGD
  • response to nicotine Source: RGD
  • response to nutrient Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to peptide hormone Source: RGD
  • response to phenylpropanoid Source: RGD
  • response to vitamin E Source: RGD

Keywordsi

Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulator Bcl-2
Gene namesi
Name:Bcl2
Synonyms:Bcl-2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2199 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430501 – 236Apoptosis regulator Bcl-2Add BLAST236

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei69Phosphothreonine; by MAPK8By similarity1
Modified residuei70Phosphoserine; by MAPK8 and PKCBy similarity1
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 similarity).By similarity
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 (By similarity).By similarity
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

PaxDbiP49950

PTM databases

iPTMnetiP49950
PhosphoSitePlusiP49950

Expressioni

Tissue specificityi

Expressed in a variety of tissues, with highest levels in reproductive tissues. In the adult brain, expression is localized in mitral cells of the olfactory bulb, granule and pyramidal neurons of hippocampus, pontine nuclei, cerebellar granule neurons, and in ependymal cells. In prenatal brain, expression is higher and localized in the neuroepithelium and in the cortical plate.

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. Also interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, FKBP8, MRPL41, and TP53BP2. 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 G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex (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

GO - Molecular functioni

  • BH domain binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: GO_Central

Protein-protein interaction databases

BioGridi246412, 1 interactor
ComplexPortaliCPX-2018 BCL-2 dimer
CPX-2020 BAD:BCL-2 complex
CPX-2023 BID:BCL-2 complex
CPX-2028 PUMA:BCL-2 complex
CPX-2035 BIM:BCL-2 complex
DIPiDIP-30849N
IntActiP49950, 3 interactors
STRINGi10116.ENSRNOP00000003768

Structurei

3D structure databases

ProteinModelPortaliP49950
SMRiP49950
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.By similarity
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
HOGENOMiHOG000056452
HOVERGENiHBG004472
InParanoidiP49950
KOiK02161
PhylomeDBiP49950

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

Sequencei

Sequence statusi: Complete.

P49950-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DTGDEDSAPL RAAPTPGIFS
60 70 80 90 100
FQPESNRTPA VHRDTAARTS PLRPLVANAG 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):26,622
Last modified:November 1, 1997 - v2
Checksum:iE7688CB9071A872A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42A → R in AAA77687 (PubMed:7828536).Curated1
Sequence conflicti157E → G in AAA53662 (PubMed:8144041).Curated1
Sequence conflicti164S → Y in AAA77687 (PubMed:7828536).Curated1
Sequence conflicti212L → Q in AAA77687 (PubMed:7828536).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L14680 mRNA Translation: AAA53662.1
U34964 mRNA Translation: AAA77687.1
S74122 mRNA No translation available.
PIRiI53744
I67432
RefSeqiNP_058689.1, NM_016993.1
UniGeneiRn.9996

Genome annotation databases

GeneIDi24224
KEGGirno:24224
UCSCiRGD:2199 rat

Similar proteinsi

Entry informationi

Entry nameiBCL2_RAT
AccessioniPrimary (citable) accession number: P49950
Secondary accession number(s): Q62837, Q64032
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: June 20, 2018
This is version 145 of the entry and version 2 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

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