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Protein

Apoptosis regulator Bcl-2

Gene

Bcl2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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
  • negative regulation of apoptotic process Source: UniProtKB
  • 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 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 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 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
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Names & Taxonomyi

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

Organism-specific databases

RGDi2199. Bcl2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei209 – 23022HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: RGD
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial outer membrane Source: GO_Central
  • mitochondrion Source: RGD
  • nuclear membrane Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 236236Apoptosis regulator Bcl-2PRO_0000143050Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei69 – 691Phosphothreonine; by MAPK8By similarity
Modified residuei70 – 701Phosphoserine; by MAPK8 and PKCBy similarity
Modified residuei84 – 841Phosphoserine; by MAPK8By similarity

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 PARK2, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei34 – 352Cleavage; by caspasesBy similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP49950.

PTM databases

iPTMnetiP49950.
PhosphoSiteiP49950.

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 interaction.
DIPiDIP-30849N.
IntActiP49950. 2 interactions.
STRINGi10116.ENSRNOP00000003768.

Structurei

3D structure databases

ProteinModelPortaliP49950.
SMRiP49950. Positions 3-204.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi10 – 3021BH4Add
BLAST
Motifi90 – 10415BH3Add
BLAST
Motifi133 – 15220BH1Add
BLAST
Motifi184 – 19916BH2Add
BLAST

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

InterProiIPR013278. 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.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSiPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTiSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00865. bcl-2. 1 hit.
PROSITEiPS50062. 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.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421A → R in AAA77687 (PubMed:7828536).Curated
Sequence conflicti157 – 1571E → G in AAA53662 (PubMed:8144041).Curated
Sequence conflicti164 – 1641S → Y in AAA77687 (PubMed:7828536).Curated
Sequence conflicti212 – 2121L → Q in AAA77687 (PubMed:7828536).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP49950.
SMRiP49950. Positions 3-204.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246412. 1 interaction.
DIPiDIP-30849N.
IntActiP49950. 2 interactions.
STRINGi10116.ENSRNOP00000003768.

PTM databases

iPTMnetiP49950.
PhosphoSiteiP49950.

Proteomic databases

PaxDbiP49950.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24224.
KEGGirno:24224.
UCSCiRGD:2199. rat.

Organism-specific databases

CTDi596.
RGDi2199. Bcl2.

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
HOGENOMiHOG000056452.
HOVERGENiHBG004472.
InParanoidiP49950.
KOiK02161.
PhylomeDBiP49950.

Miscellaneous databases

PROiP49950.

Family and domain databases

InterProiIPR013278. 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.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSiPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTiSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00865. bcl-2. 1 hit.
PROSITEiPS50062. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBCL2_RAT
AccessioniPrimary (citable) accession number: P49950
Secondary accession number(s): Q62837, Q64032
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 1, 1997
Last modified: July 6, 2016
This is version 130 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.