Q9JJV8 (BCL2_CRIGR) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 87. History...
Names and origin
|Protein names||Recommended name:|
Apoptosis regulator Bcl-2
|Organism||Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)|
|Taxonomic identifier||10029 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Cricetulus|
|Sequence length||236 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
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.
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3 By similarity.
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 By similarity. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases By similarity. 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.
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. Ref.2
Monoubiquitinated by PARK2, leading to increase its stability By similarity.
Belongs to the Bcl-2 family.
|Cellular component||Endoplasmic reticulum|
Mitochondrion outer membrane
|Gene Ontology (GO)|
Inferred from electronic annotation. Source: UniProtKB-KWnegative regulation of apoptotic process
Inferred from electronic annotation. Source: InterPro
|Cellular_component||endoplasmic reticulum membrane|
Inferred from electronic annotation. Source: UniProtKB-SubCellintegral to membrane
Inferred from electronic annotation. Source: UniProtKB-KWmitochondrial outer membrane
Inferred from electronic annotation. Source: UniProtKB-SubCellnuclear membrane
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 236||236||Apoptosis regulator Bcl-2||PRO_0000143047|
|Transmembrane||209 – 230||22||Helical; Potential|
|Motif||10 – 30||21||BH4|
|Motif||90 – 104||15||BH3|
|Motif||133 – 152||20||BH1|
|Motif||184 – 199||16||BH2|
|Site||64 – 65||2||Cleavage; by caspase-3 and caspase-9|
Amino acid modifications
|Modified residue||69||1||Phosphothreonine; by MAPK8 By similarity|
|Modified residue||70||1||Phosphoserine; by MAPK8 and PKC By similarity|
|Modified residue||84||1||Phosphoserine; by MAPK8 By similarity|
|||"Cloning and functional analysis of cDNA encoding the hamster Bcl-2 protein."|
Tomicic M.T., Christmann M., Kaina B.
Biochem. Biophys. Res. Commun. 275:899-903(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Hamster Bcl-2 protein is cleaved in vitro and in cells by caspase-9 and caspase-3."|
Tomicic M.T., Kaina B.
Biochem. Biophys. Res. Commun. 281:404-408(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CLEAVAGE BY CASPASES.
|AJ271720 mRNA. Translation: CAB92245.1.|
3D structure databases
|SMR||Q9JJV8. Positions 3-204. |
Protein-protein interaction databases
|IntAct||Q9JJV8. 1 interaction.|
Protocols and materials databases
Family and domain databases
|InterPro||IPR013278. Apop_reg_Bcl2. |
|PANTHER||PTHR11256. PTHR11256. 1 hit. |
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
|Pfam||PF00452. Bcl-2. 1 hit. |
PF02180. BH4. 1 hit.
|PRINTS||PR01863. APOPREGBCL2. |
|SMART||SM00265. BH4. 1 hit. |
|TIGRFAMs||TIGR00865. bcl-2. 1 hit. |
|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.
|Accession||Primary (citable) accession number: Q9JJV8|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families