Q9JJV8 (BCL2_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis regulator Bcl-2

Gene names

Name:

BCL2

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

Protein attributes

Sequence length	236 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein.
Domain	The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3 By similarity.
Post-translational modification	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.
Sequence similarities	Belongs to the Bcl-2 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Endoplasmic reticulum Membrane Mitochondrion Mitochondrion outer membrane Nucleus
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW regulation of apoptotic process Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 236	236	Apoptosis regulator Bcl-2		PRO_0000143047
Regions
	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
Sites
	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

Sequences

	Sequence		Length	Mass (Da)
	Q9JJV8 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: BECADF1EF3337228	FASTA	236	26,491
	10 20 30 40 50 60 MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DVGDVDAAPL GAAPTPGIFS FQPESNPTPA 70 80 90 100 110 120 VHRDMAARTS PLRPIVATTG PTLSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP 130 140 150 160 170 180 FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR 190 200 210 220 230 HLHTWIQDNG GWDAFVELYG PSVRPLFDFS WLSLKTLLSL ALVGACITLG TYLGHK

References

[1]	"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: 10973819] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Ovary.
[2]	"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: 11181062] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CLEAVAGE BY CASPASES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ271720 mRNA. Translation: CAB92245.1.
PIR	JC7383.
3D structure databases
ProteinModelPortal	Q9JJV8.
SMR	Q9JJV8. Positions 3-204.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9JJV8. 1 interaction.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG004472.
Family and domain databases
InterPro	IPR013278. Apop_reg_Bcl2. IPR002475. Bcl2-like_apoptosis. IPR000712. Bcl2_BH. IPR020717. Bcl2_BH1_motif_CS. IPR020726. Bcl2_BH2_motif_CS. IPR020728. Bcl2_BH3_motif_CS. IPR003093. Bcl2_BH4. IPR020731. Bcl2_BH4_motif_CS. IPR004725. Bcl2_reg. [Graphical view]
Pfam	PF00452. Bcl-2. 1 hit. PF02180. BH4. 1 hit. [Graphical view]
PRINTS	PR01863. APOPREGBCL2. PR01862. BCL2FAMILY.
SMART	SM00337. BCL. 1 hit. SM00265. BH4. 1 hit. [Graphical view]
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. [Graphical view]
ProtoNet	Search...
Other
PMAP-CutDB	Q9JJV8.

Entry information

Entry name

BCL2_CRIGR

Accession

Primary (citable) accession number: Q9JJV8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program