Reviewed, UniProtKB/Swiss-Prot Q9JJV8 (BCL2_CRIGR)

Names and origin

Protein names

Recommended name:
    Apoptosis regulator Bcl-2

Gene names

Name:

BCL2

Organism

Cricetulus griseus (Chinese hamster)

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.
Sequence processing	The displayed sequence is not processed.
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. Also interacts with FKBP8, APAF1, RAF-1, TP53BP2, BBC3, BCL2L1, MRPL41 and BNIPL 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 RAF-1 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. 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
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
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of apoptosis 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
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP8	Q14790	1	EBI-1749099,EBI-78060	From a different organism.

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	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	70	1	Phosphoserine; by PKC By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9JJV8-1 [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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ271720 mRNA. Translation: CAB92245.1.
PIR	JC7383.
3D structure databases
HSSP	HSSP built from PDB template 1GJH based on UniProtKB P10415.
SMR	Q9JJV8. Positions 41-204.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9JJV8. 1 interaction.
Phylogenomic databases
HOVERGEN	Q9JJV8.
Family and domain databases
InterPro	IPR013278. Apop_reg_Bcl2. IPR002475. BCL2_apoptsis. IPR000712. Bcl2_BH. IPR003093. Bcl2_BH4. 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 Resources
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:	June 16, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)