P10417 (BCL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis regulator Bcl-2

Gene names

Name:	Bcl2
Synonyms:	Bcl-2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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 By similarity. Also interacts with APAF1, BBC3, BCL2L1, BNIPL, 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 EI24. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with PPIF; the interaction is impaired by CsA By similarity. Interacts with BOP By similarity. Ref.8
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.
Domain	The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
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). Ref.6 Ref.7 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. 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
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell homeostasis Inferred from mutant phenotype PubMed 7650488PubMed 8170972. Source: MGI B cell lineage commitment Inferred from mutant phenotype PubMed 8788039. Source: MGI B cell proliferation Inferred from sequence orthology PubMed 1373874. Source: MGI B cell receptor signaling pathway Inferred from electronic annotation. Source: Compara CD8-positive, alpha-beta T cell lineage commitment Inferred from mutant phenotype PubMed 8170972. Source: MGI G1/S transition of mitotic cell cycle Inferred from mutant phenotype PubMed 12855558PubMed 14660795. Source: MGI T cell differentiation in thymus Inferred from mutant phenotype PubMed 8170972PubMed 9028316. Source: MGI T cell homeostasis Inferred from mutant phenotype PubMed 7650488PubMed 8170972. Source: MGI actin filament organization Inferred from mutant phenotype PubMed 9950951. Source: MGI axon regeneration Inferred from direct assay PubMed 9009190. Source: MGI behavioral fear response Inferred from mutant phenotype PubMed 16095731. Source: MGI branching involved in ureteric bud morphogenesis Inferred from direct assay PubMed 14699151. Source: MGI cell aging Inferred from mutant phenotype PubMed 8372353. Source: MGI cell growth Inferred from mutant phenotype PubMed 8084613. Source: MGI cell-cell adhesion Inferred from mutant phenotype PubMed 15292044. Source: MGI cellular response to organic substance Inferred from direct assay PubMed 12606450. Source: MGI cochlear nucleus development Inferred from mutant phenotype PubMed 11027399. Source: MGI defense response to virus Inferred from electronic annotation. Source: Compara developmental growth Inferred from mutant phenotype PubMed 15818405. Source: MGI digestive tract morphogenesis Inferred from mutant phenotype PubMed 7812968. Source: MGI ear development Inferred from mutant phenotype PubMed 11709185PubMed 8170972. Source: MGI endoplasmic reticulum calcium ion homeostasis Inferred from genetic interaction PubMed 15613488. Source: MGI focal adhesion assembly Inferred from mutant phenotype PubMed 15292044. Source: MGI gland morphogenesis Inferred from mutant phenotype PubMed 7812968. Source: MGI glomerulus development Inferred from mutant phenotype PubMed 8623928. Source: MGI hair follicle morphogenesis Inferred from mutant phenotype PubMed 8402909. Source: UniProtKB homeostasis of number of cells within a tissue Inferred from mutant phenotype PubMed 16427619PubMed 9241272. Source: MGI intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from sequence or structural similarity PubMed 15776018. Source: MGI lymphoid progenitor cell differentiation Inferred from mutant phenotype PubMed 9028316. Source: MGI male gonad development Inferred from genetic interaction PubMed 9241272. Source: MGI melanin metabolic process Inferred from mutant phenotype PubMed 11709185. Source: MGI melanocyte differentiation Inferred from mutant phenotype PubMed 11709185PubMed 12086670PubMed 8758925. Source: MGI mesenchymal cell development Inferred from mutant phenotype PubMed 8623928. Source: MGI metanephros development Inferred from mutant phenotype PubMed 7840250PubMed 8623928. Source: MGI negative regulation of anoikis Inferred from electronic annotation. Source: Compara negative regulation of apoptotic signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of calcium ion transport into cytosol Inferred from genetic interaction PubMed 15613488. Source: MGI negative regulation of cell growth Inferred from mutant phenotype PubMed 12855558. Source: MGI negative regulation of cell migration Inferred from mutant phenotype PubMed 15292044. Source: MGI negative regulation of cellular pH reduction Inferred from electronic annotation. Source: Compara negative regulation of mitotic cell cycle Inferred from direct assay PubMed 9241272. Source: MGI negative regulation of myeloid cell apoptotic process Inferred from direct assay PubMed 9202146. Source: MGI negative regulation of neuron apoptotic process Inferred from direct assay PubMed 7472523PubMed 8625820. Source: MGI negative regulation of ossification Inferred from mutant phenotype PubMed 9008714. Source: MGI negative regulation of osteoblast proliferation Inferred from mutant phenotype PubMed 10193316. Source: MGI negative regulation of retinal cell programmed cell death Inferred from mutant phenotype PubMed 10321489. Source: MGI neuron apoptotic process Inferred from mutant phenotype PubMed 7546744. Source: MGI oocyte development Inferred from mutant phenotype PubMed 7628407. Source: MGI organ growth Inferred from mutant phenotype PubMed 7812968PubMed 8623928. Source: MGI ossification Inferred from mutant phenotype PubMed 10193316. Source: MGI ovarian follicle development Inferred from mutant phenotype PubMed 7628407. Source: MGI peptidyl-serine phosphorylation Inferred from direct assay PubMed 14660795. Source: MGI peptidyl-threonine phosphorylation Inferred from direct assay PubMed 14660795. Source: MGI pigment granule organization Inferred from mutant phenotype PubMed 8758925. Source: MGI positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of catalytic activity Inferred from mutant phenotype PubMed 17382917. Source: MGI positive regulation of cell growth Inferred from sequence orthology PubMed 8022822. Source: MGI positive regulation of cell proliferation Inferred from direct assay PubMed 11983915. Source: UniProtKB positive regulation of melanocyte differentiation Inferred from mutant phenotype PubMed 16427619. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype PubMed 11709185. Source: MGI positive regulation of neuron maturation Inferred from mutant phenotype PubMed 9547242. Source: MGI positive regulation of peptidyl-serine phosphorylation Inferred from genetic interaction PubMed 15613488. Source: MGI positive regulation of skeletal muscle fiber development Inferred from mutant phenotype PubMed 11146504. Source: MGI positive regulation of smooth muscle cell migration Inferred from mutant phenotype PubMed 17382917. Source: MGI post-embryonic development Inferred from mutant phenotype PubMed 10674380PubMed 11709185PubMed 7812968PubMed 8170972PubMed 8755480. Source: MGI protein dephosphorylation Inferred from direct assay PubMed 16717086. Source: MGI protein polyubiquitination Inferred from sequence orthology PubMed 16717086. Source: MGI reactive oxygen species metabolic process Inferred from mutant phenotype PubMed 10726970PubMed 12855558PubMed 9681465. Source: MGI regulation of cell-matrix adhesion Inferred from mutant phenotype PubMed 15292044. Source: MGI regulation of glycoprotein biosynthetic process Inferred from mutant phenotype PubMed 15292044. Source: MGI regulation of mitochondrial membrane permeability Inferred from direct assay PubMed 9843949. Source: HGNC regulation of mitochondrial membrane potential Inferred from direct assay PubMed 9843949. Source: HGNC regulation of nitrogen utilization Inferred from genetic interaction PubMed 9241272. Source: MGI regulation of protein heterodimerization activity Inferred from electronic annotation. Source: Compara regulation of protein homodimerization activity Inferred from electronic annotation. Source: Compara regulation of protein localization Inferred from mutant phenotype PubMed 9950951. Source: MGI regulation of protein stability Inferred from mutant phenotype PubMed 14660795. Source: MGI regulation of transmembrane transporter activity Inferred from electronic annotation. Source: Compara regulation of viral genome replication Inferred from direct assay PubMed 16950491. Source: UniProtKB release of cytochrome c from mitochondria Inferred from direct assay PubMed 9843949. Source: HGNC renal system process Inferred from mutant phenotype PubMed 8760259. Source: MGI response to DNA damage stimulus Inferred from electronic annotation. Source: Compara response to UV-B Inferred from mutant phenotype PubMed 10200548. Source: MGI response to acid Inferred from direct assay PubMed 7675327. Source: MGI response to cytokine stimulus Inferred from mutant phenotype PubMed 12855558. Source: MGI response to drug Inferred from direct assay PubMed 9098922. Source: MGI response to external stimulus Inferred from mutant phenotype PubMed 10488913. Source: MGI response to gamma radiation Inferred from mutant phenotype PubMed 10815637PubMed 17068116PubMed 8170972PubMed 8372353. Source: MGI response to glucocorticoid stimulus Inferred from direct assay PubMed 8313913. Source: MGI response to hydrogen peroxide Inferred from mutant phenotype PubMed 12855558. Source: MGI response to iron ion Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to toxin Inferred from mutant phenotype PubMed 10602483. Source: MGI spleen development Inferred from mutant phenotype PubMed 15818405. Source: MGI thymus development Inferred from mutant phenotype PubMed 15818405PubMed 9241272. Source: MGI
Cellular_component	cytosol Inferred from direct assay PubMed 12050152PubMed 14551195PubMed 8030757. Source: MGI endoplasmic reticulum membrane Inferred from direct assay PubMed 15613488. Source: MGI mitochondrial membrane Inferred from direct assay PubMed 11980919. Source: MGI mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell myelin sheath Inferred from direct assay PubMed 7953633. Source: MGI nuclear membrane Inferred from direct assay PubMed 8030757. Source: MGI pore complex Inferred from electronic annotation. Source: Compara
Molecular_function	channel activity Inferred from electronic annotation. Source: Compara protein phosphatase 2A binding Inferred from direct assay PubMed 16717086. Source: MGI sequence-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: P10417-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Beta (identifier: P10417-2)

The sequence of this isoform differs from the canonical sequence as follows:
     193-236: DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK → VGACLVE

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 236	236	Apoptosis regulator Bcl-2		PRO_0000143049
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
	Modified residue	84	1	Phosphoserine; by MAPK8 By similarity
Natural variations
	Alternative sequence	193 – 236	44	DAFVE…YLGHK → VGACLVE in isoform Beta.		VSP_000513
Experimental info
	Sequence conflict	64	1	D → E in AAA37281. Ref.1
	Sequence conflict	64	1	D → E in AAA37282. Ref.1
	Sequence conflict	89	1	V → C in AAA37281. Ref.1
	Sequence conflict	89	1	V → C in AAA37282. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified October 3, 2012. Version 3. Checksum: 80FDCFE78C735092	FASTA	236	26,407
	10 20 30 40 50 60 MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDADAAPL GAAPTPGIFS FQPESNPMPA 70 80 90 100 110 120 VHRDMAARTS PLRPLVATAG 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
	Isoform Beta [UniParc]. Checksum: F13C8037262BA955	FASTA	199	22,281
	10 20 30 40 50 60 MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDADAAPL GAAPTPGIFS FQPESNPMPA 70 80 90 100 110 120 VHRDMAARTS PLRPLVATAG PALSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP 130 140 150 160 170 180 FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR 190 HLHTWIQDNG GWVGACLVE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular analysis of mbcl-2: structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma." Negrini M., Silini E., Kozak C., Tsujimoto Y., Croce C.M. Cell 49:455-463(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA AND BETA). Strain: BALB/c. Tissue: Liver.
[2]	"Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo." Eguchi Y., Ewert D.L., Tsujimoto Y. Nucleic Acids Res. 20:4187-4192(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 221-222.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Olfactory epithelium.
[6]	"Bcl-2 phosphorylation required for anti-apoptosis function." Ito T., Deng X., Carr B., May W.S. Jr. J. Biol. Chem. 272:11671-11673(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY PKC, MUTAGENESIS OF SERINE RESIDUES.
[7]	"Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A." Deng X., Ito T., Carr B., Mumby M., May W.S. Jr. J. Biol. Chem. 273:34157-34163(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DEPHOSPHORYLATION BY PP2A.
[8]	"Apoptosis factor EI24/PIG8 is a novel endoplasmic reticulum-localized Bcl-2-binding protein which is associated with suppression of breast cancer invasiveness." Zhao X., Ayer R.E., Davis S.L., Ames S.J., Florence B., Torchinsky C., Liou J.S., Shen L., Spanjaard R.A. Cancer Res. 65:2125-2129(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EI24.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L31532, M16506 Genomic DNA. Translation: AAA37282.1. M16506 Genomic DNA. Translation: AAA37281.1. AC122842 Genomic DNA. No translation available. AC162916 Genomic DNA. No translation available. CH466520 Genomic DNA. Translation: EDL39862.1. BC095964 mRNA. Translation: AAH95964.1.
IPI	IPI00111518. IPI00227012.
PIR	TVMSA1. A25960. TVMSB1. B25960.
RefSeq	NP_033871.2. NM_009741.3.
UniGene	Mm.257460.
3D structure databases
ProteinModelPortal	P10417.
SMR	P10417. Positions 3-204.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-1065N.
IntAct	P10417. 6 interactions.
MINT	MINT-209615.
PTM databases
PhosphoSite	P10417.
Proteomic databases
PaxDb	P10417.
PRIDE	P10417.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329.
GeneID	12043.
KEGG	mmu:12043.
Organism-specific databases
CTD	596.
MGI	MGI:88138. Bcl2.
Phylogenomic databases
eggNOG	NOG275924.
GeneTree	ENSGT00530000062935.
HOGENOM	HOG000056452.
HOVERGEN	HBG004472.
InParanoid	P10417.
KO	K02161.
OMA	EWDAGDA.
OrthoDB	EOG4X97J4.
Gene expression databases
CleanEx	MM_BCL2.
Genevestigator	P10417.
GermOnline	ENSMUSG00000057329. Mus musculus.
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
ChiTaRS	BCL2. mouse.
NextBio	280313.
SOURCE	Search...

Entry information

Entry name

BCL2_MOUSE

Accession

Primary (citable) accession number: P10417
Secondary accession number(s): P10418, Q4VBF6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 3, 2012
Last modified:	May 1, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program