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Protein

Apoptosis regulator Bcl-2

Gene

BCL2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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) (By similarity). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulator Bcl-2
Gene namesi
Name:BCL2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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
Transmembranei202 – 223HelicalSequence analysisAdd BLAST22

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430461 – 229Apoptosis regulator Bcl-2Add BLAST229

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62Phosphothreonine; by MAPK8By similarity1
Modified residuei63Phosphoserine; by MAPK8 and PKCBy similarity1
Modified residuei77Phosphoserine; by MAPK8By similarity1

Post-translational modificationi

Phosphorylation/dephosphorylation on Ser-63 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-63 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle (By similarity). 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-62, Ser-63 and Ser-77, 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

PaxDbiO02718
PRIDEiO02718

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, EI24, 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 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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000025701

Structurei

3D structure databases

ProteinModelPortaliO02718
SMRiO02718
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi10 – 30BH4Add BLAST21
Motifi83 – 97BH3Add BLAST15
Motifi126 – 145BH1Add BLAST20
Motifi177 – 192BH2Add BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi64 – 68Poly-Pro5
Compositional biasi69 – 72Poly-Ala4

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
HOVERGENiHBG004472
InParanoidiO02718

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.

O02718-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHAGGTGYD NREIVMKYIH YKLSQRGYEW DAGDAGAAPP GAAPAPGILS
60 70 80 90 100
SQPGRTPAPS RTSPPPPPAA AAGPAPSPVP PVVHLTLRQA GDDFSRRYRR
110 120 130 140 150
DFAEMSSQLH LTPFTARERF ATVVEELFRD GVNWGRIVAF FEFGGVMCVE
160 170 180 190 200
SVNREMSPLV DSIALWMTEY LNRHLHTWIQ DNGGWDAFVE LYGPSMRPLF
210 220
DFSWLSLKAL LSLALVGACI TLGAYLGHK
Length:229
Mass (Da):25,100
Last modified:July 1, 1997 - v1
Checksum:iAD1DD0AF98FFF11D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92434 mRNA Translation: AAB53319.1
UniGeneiBt.48090

Similar proteinsi

Entry informationi

Entry nameiBCL2_BOVIN
AccessioniPrimary (citable) accession number: O02718
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: July 1, 1997
Last modified: October 25, 2017
This is version 124 of the entry and version 1 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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