P49950 (BCL2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis regulator Bcl-2

Gene names

Name:	Bcl2
Synonyms:	Bcl-2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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).
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 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. Ref.4
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein.
Tissue specificity	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.
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. 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. 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. 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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 17302035. Source: RGD brain development Inferred from expression pattern PubMed 18058945. Source: RGD glial cell apoptotic process Inferred from expression pattern PubMed 18931364. Source: RGD negative regulation of apoptotic process Inferred from direct assay PubMed 11879647. Source: RGD oligodendrocyte differentiation Inferred from expression pattern PubMed 12787069. Source: RGD ovarian follicle development Inferred from expression pattern PubMed 17570453. Source: RGD regulation of mitochondrial membrane permeability Inferred from sequence or structural similarity PubMed 9843949. Source: HGNC regulation of mitochondrial membrane potential Inferred from sequence or structural similarity PubMed 9843949. Source: HGNC release of cytochrome c from mitochondria Inferred from sequence or structural similarity PubMed 9843949. Source: HGNC response to L-ascorbic acid Inferred from expression pattern PubMed 18758938. Source: RGD response to aluminum ion Inferred from expression pattern PubMed 17967740. Source: RGD response to cAMP Inferred from expression pattern PubMed 18086876. Source: RGD response to caffeine Inferred from expression pattern PubMed 17236787. Source: RGD response to copper ion Inferred from expression pattern PubMed 18289470. Source: RGD response to corticosterone stimulus Inferred from expression pattern PubMed 17562391. Source: RGD response to cytokine stimulus Inferred from expression pattern PubMed 18832793. Source: RGD response to drug Inferred from expression pattern PubMed 18284815. Source: RGD response to estrogen stimulus Inferred from expression pattern PubMed 16084662. Source: RGD response to ethanol Inferred from expression pattern PubMed 15469889. Source: RGD response to folic acid Inferred from expression pattern PubMed 18156304. Source: RGD response to heat Inferred from expression pattern PubMed 17131910. Source: RGD response to hypoxia Inferred from expression pattern PubMed 16445580. Source: RGD response to insulin stimulus Inferred from expression pattern PubMed 18758938. Source: RGD response to nicotine Inferred from expression pattern PubMed 15332118. Source: RGD
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 mitochondrion Inferred from direct assay PubMed 15341589. Source: RGD 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_0000143050
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	34 – 35	2	Cleavage; by caspases By similarity
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
Experimental info
	Sequence conflict	42	1	A → R in AAA77687. Ref.2
	Sequence conflict	157	1	E → G in AAA53662. Ref.1
	Sequence conflict	164	1	S → Y in AAA77687. Ref.2
	Sequence conflict	212	1	L → Q in AAA77687. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P49950 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: E7688CB9071A872A	FASTA	236	26,622
	10 20 30 40 50 60 MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DTGDEDSAPL RAAPTPGIFS FQPESNRTPA 70 80 90 100 110 120 VHRDTAARTS PLRPLVANAG PALSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP 130 140 150 160 170 180 FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR 190 200 210 220 230 HLHTWIQDNG GWDAFVELYG PSMRPLFDFS WLSLKTLLSL ALVGACITLG AYLGHK

References

[1]	"Cloning and sequencing of a cDNA encoding the rat Bcl-2 protein." Sato T., Irie S., Krajewski S., Reed J.C. Gene 140:291-292(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Expression of members of the Bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased Bax and constitutive Bcl-2 and Bcl-xlong messenger ribonucleic acid levels." Tilly J.L., Tilly K.I., Kenton M.L., Johnson A.L. Endocrinology 136:232-241(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Ovary.
[3]	"bcl-2 messenger RNA is localized in neurons of the developing and adult rat brain." Castren E., Ohga Y., Berzaghi M.P., Tzimagiorgis G., Thoenen H., Lindholm D. Neuroscience 61:165-177(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-172.
[4]	"Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect." Eliseev R.A., Malecki J., Lester T., Zhang Y., Humphrey J., Gunter T.E. J. Biol. Chem. 284:9692-9699(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPIF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L14680 mRNA. Translation: AAA53662.1. U34964 mRNA. Translation: AAA77687.1. S74122 mRNA. No translation available.
IPI	IPI00325212.
PIR	I53744. I67432.
RefSeq	NP_058689.1. NM_016993.1.
UniGene	Rn.9996.
3D structure databases
ProteinModelPortal	P49950.
SMR	P49950. Positions 3-204.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-30849N.
IntAct	P49950. 2 interactions.
STRING	10116.ENSRNOP00000003768.
PTM databases
PhosphoSite	P49950.
Proteomic databases
PaxDb	P49950.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24224.
KEGG	rno:24224.
UCSC	RGD:2199. rat.
Organism-specific databases
CTD	596.
RGD	2199. Bcl2.
Phylogenomic databases
eggNOG	NOG275924.
HOGENOM	HOG000056452.
HOVERGEN	HBG004472.
InParanoid	P49950.
KO	K02161.
OrthoDB	EOG4X97J4.
Gene expression databases
ArrayExpress	P49950.
Genevestigator	P49950.
GermOnline	ENSRNOG00000002791. Rattus norvegicus.
Family and domain databases
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. IPR026298. Blc2_fam. [Graphical view]
PANTHER	PTHR11256. PTHR11256. 1 hit. PTHR11256:SF11. PTHR11256:SF11. 1 hit.
Pfam	PF00452. Bcl-2. 1 hit. PF02180. BH4. 1 hit. [Graphical view]
PRINTS	PR01863. APOPREGBCL2. PR01862. BCL2FAMILY.
SMART	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
NextBio	602665.

Entry information

Entry name

BCL2_RAT

Accession

Primary (citable) accession number: P49950
Secondary accession number(s): Q62837, Q64032

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program