P10415 (BCL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis regulator Bcl-2

Gene names

Name:

BCL2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	239 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). Ref.22
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. Interacts with EI24 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. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with BOP. Ref.11 Ref.13 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27
Subcellular location	Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein Ref.9.
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-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A) By similarity. Ref.15 Ref.22 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.12 Monoubiquitinated by PARK2, leading to increase its stability.
Involvement in disease	A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
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 Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell homeostasis Inferred from electronic annotation. Source: Compara B cell lineage commitment Inferred from electronic annotation. Source: Compara B cell proliferation Inferred from direct assay PubMed 1373874. Source: MGI B cell receptor signaling pathway Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB CD8-positive, alpha-beta T cell lineage commitment Inferred from electronic annotation. Source: Compara G1/S transition of mitotic cell cycle Inferred from electronic annotation. Source: Compara T cell differentiation in thymus Inferred from electronic annotation. Source: Compara T cell homeostasis Inferred from electronic annotation. Source: Compara actin filament organization Inferred from electronic annotation. Source: Compara axon regeneration Inferred from electronic annotation. Source: Compara behavioral fear response Inferred from electronic annotation. Source: Compara branching involved in ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara cell aging Inferred from electronic annotation. Source: Compara cell growth Inferred from electronic annotation. Source: Compara cell-cell adhesion Inferred from electronic annotation. Source: Compara cellular response to organic substance Inferred from electronic annotation. Source: Compara cochlear nucleus development Inferred from electronic annotation. Source: Compara defense response to virus Inferred from direct assay PubMed 10620603. Source: UniProtKB developmental growth Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara ear development Inferred from electronic annotation. Source: Compara endoplasmic reticulum calcium ion homeostasis Inferred from electronic annotation. Source: Compara female pregnancy Non-traceable author statement PubMed 11530860. Source: UniProtKB focal adhesion assembly Inferred from electronic annotation. Source: Compara gland morphogenesis Inferred from electronic annotation. Source: Compara glomerulus development Inferred from electronic annotation. Source: Compara hair follicle morphogenesis Inferred from electronic annotation. Source: Compara homeostasis of number of cells within a tissue Inferred from electronic annotation. Source: Compara humoral immune response Traceable author statement PubMed 1908951. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from direct assay PubMed 15776018. Source: MGI lymphoid progenitor cell differentiation Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara melanin metabolic process Inferred from electronic annotation. Source: Compara melanocyte differentiation Inferred from electronic annotation. Source: Compara mesenchymal cell development Inferred from electronic annotation. Source: Compara metanephros development Inferred from electronic annotation. Source: Compara negative regulation of anoikis Inferred from mutant phenotype PubMed 15006356. Source: UniProtKB negative regulation of apoptotic signaling pathway Inferred from mutant phenotype PubMed 20097879. Source: UniProtKB negative regulation of autophagy Traceable author statement PubMed 18309324. Source: UniProtKB negative regulation of calcium ion transport into cytosol Inferred from electronic annotation. Source: Compara negative regulation of cell growth Inferred from electronic annotation. Source: Compara negative regulation of cell migration Inferred from electronic annotation. Source: Compara negative regulation of cellular pH reduction Inferred from direct assay PubMed 10506221. Source: UniProtKB negative regulation of mitochondrial depolarization Traceable author statement PubMed 9027314. Source: UniProtKB negative regulation of mitotic cell cycle Inferred from electronic annotation. Source: Compara negative regulation of myeloid cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from direct assay PubMed 7546744. Source: MGI negative regulation of ossification Inferred from electronic annotation. Source: Compara negative regulation of osteoblast proliferation Inferred from electronic annotation. Source: Compara negative regulation of retinal cell programmed cell death Inferred from electronic annotation. Source: Compara neuron apoptotic process Traceable author statement PubMed 16167175. Source: HGNC nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Traceable author statement. Source: Reactome oocyte development Inferred from electronic annotation. Source: Compara organ growth Inferred from electronic annotation. Source: Compara ossification Inferred from electronic annotation. Source: Compara ovarian follicle development Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara pigment granule organization Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB positive regulation of catalytic activity Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from direct assay PubMed 8022822. Source: MGI positive regulation of melanocyte differentiation Inferred from electronic annotation. Source: Compara positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara positive regulation of neuron maturation Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of skeletal muscle fiber development Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell migration Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara protein dephosphorylation Inferred from electronic annotation. Source: Compara protein polyubiquitination Inferred from direct assay PubMed 16717086. Source: MGI reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara regulation of calcium ion transport Inferred from direct assay PubMed 8022822. Source: MGI regulation of cell-matrix adhesion Inferred from electronic annotation. Source: Compara regulation of glycoprotein biosynthetic process Inferred from electronic annotation. Source: Compara 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 regulation of nitrogen utilization Inferred from electronic annotation. Source: Compara regulation of protein heterodimerization activity Inferred from direct assay PubMed 9111042. Source: UniProtKB regulation of protein homodimerization activity Inferred from direct assay PubMed 9111042. Source: UniProtKB regulation of protein localization Inferred from electronic annotation. Source: Compara regulation of protein stability Inferred from electronic annotation. Source: Compara regulation of transmembrane transporter activity Inferred from direct assay PubMed 9219694. Source: BHF-UCL regulation of viral genome replication Inferred from electronic annotation. Source: Compara release of cytochrome c from mitochondria Non-traceable author statement PubMed 9027314. Source: UniProtKB renal system process Inferred from electronic annotation. Source: Compara response to DNA damage stimulus Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB response to UV-B Inferred from electronic annotation. Source: Compara response to acid Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from direct assay PubMed 9184696. Source: MGI response to drug Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB response to external stimulus Inferred from electronic annotation. Source: Compara response to gamma radiation Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to iron ion Inferred from direct assay PubMed 11264898. Source: UniProtKB response to nicotine Inferred from direct assay PubMed 12421819. Source: UniProtKB response to radiation Non-traceable author statement PubMed 15799693. Source: UniProtKB response to toxin Inferred from direct assay PubMed 16307838. Source: HGNC spleen development Inferred from electronic annotation. Source: Compara thymus development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay PubMed 8402648. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial outer membrane Inferred from direct assay PubMed 8402648PubMed 9027314. Source: UniProtKB myelin sheath Inferred from electronic annotation. Source: Compara nuclear membrane Inferred from direct assay PubMed 1502141PubMed 8402648PubMed 1502141PubMed 1502141. Source: UniProtKB pore complex Inferred from direct assay PubMed 9219694. Source: BHF-UCL
Molecular_function	channel activity Inferred from direct assay PubMed 9219694. Source: BHF-UCL protease binding Inferred from direct assay PubMed 10620603. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay PubMed 12086670. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-77694,EBI-77694
BAD	Q92934	5	EBI-77694,EBI-700771
Bad	Q61337	6	EBI-77694,EBI-400328	From a different organism.
BAX	Q07812	8	EBI-77694,EBI-516580
BBC3	Q9BXH1	5	EBI-77694,EBI-519884
BCAP31	P51572	2	EBI-77694,EBI-77683
BCL2L11	O43521	4	EBI-77694,EBI-526406
BCL2L11	O43521-1	3	EBI-77694,EBI-526416
BCL2L11	O43521-2	4	EBI-77694,EBI-526420
BECN1	Q14457	3	EBI-77694,EBI-949378
BID	P55957	8	EBI-77694,EBI-519672
BIK	Q13323	3	EBI-77694,EBI-700794
Bmf	Q91ZE9	2	EBI-77694,EBI-708032	From a different organism.
BNIP3L	O60238	2	EBI-77694,EBI-849893
NLRP1	Q9C000	12	EBI-77694,EBI-1220518
NR4A1	P22736	7	EBI-77694,EBI-721550
PMAIP1	Q13794	3	EBI-4370304,EBI-707392
SIVA1	O15304	2	EBI-77694,EBI-520756
TP53	P04637	3	EBI-77694,EBI-366083

Alternative products

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

Isoform Alpha (identifier: P10415-1)

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: P10415-2)

The sequence of this isoform differs from the canonical sequence as follows:
     196-239: DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK → VGASGDVS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 239

239

Apoptosis regulator Bcl-2

PRO_0000143048

Regions

Transmembrane

212 – 233

22

Helical; Potential

Motif

10 – 30

21

BH4

Motif

93 – 107

15

BH3

Motif

136 – 155

20

BH1

Motif

187 – 202

16

BH2

Sites

Site

34 – 35

2

Cleavage; by caspase-3

Amino acid modifications

Modified residue

69

1

Phosphothreonine; by MAPK8 Ref.22

Modified residue

70

1

Phosphoserine; by MAPK8 and PKC Ref.22

Modified residue

87

1

Phosphoserine; by MAPK8 Ref.22

Natural variations

Alternative sequence

196 – 239

44

DAFVE…YLGHK → VGASGDVS in isoform Beta.

VSP_000512

Natural variant

7

1

T → S. Ref.4 Ref.5

VAR_000827

Natural variant

43

1

A → T. Ref.6
Corresponds to variant rs1800477 [ dbSNP | Ensembl ].

VAR_014716

Natural variant

59

1

P → S in non-Hodgkin lymphoma; somatic mutation. Ref.8

VAR_000828

Natural variant

93

1

V → I in non-Hodgkin lymphoma; somatic mutation. Ref.8

VAR_000829

Experimental info

Mutagenesis

34

1

D → A: Abolishes cleavage by caspase-3.

Mutagenesis

64

1

D → A: No effect on cleavage by caspase-3.

Mutagenesis

145

1

G → A: No heterodimerization with BAX and loss of anti-apoptotic activity.

Mutagenesis

188

1

W → A: No heterodimerization with BAX and loss of anti-apoptotic activity.

Sequence conflict

48

1

I → F in CAA29778. Ref.4

Sequence conflict

59

1

P → T in AAA35591. Ref.3

Sequence conflict

96

1

T → A in AAD14111. Ref.8

Sequence conflict

110

1

R → G in AAD14111. Ref.8

Sequence conflict

117

1

S → R in AAA35591. Ref.3

Sequence conflict

129

1

R → C in CAA29778. Ref.4

Secondary structure

1

.

.

.

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.

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.

.

.

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.

.

.

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.

.

.

.

.

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.

239

Helix Strand Turn

Details...

Helix

11 – 25

15

Turn

32 – 34

3

Helix

92 – 107

16

Helix

109 – 116

8

Turn

123 – 125

3

Helix

126 – 137

12

Turn

138 – 140

3

Helix

144 – 163

20

Helix

169 – 184

16

Helix

186 – 191

6

Helix

195 – 201

7

Helix

203 – 205

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified April 1, 1993. Version 2. Checksum: 3C49F2B714DC9CCB	FASTA	239	26,266
	10 20 30 40 50 60 MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS SQPGHTPHPA 70 80 90 100 110 120 ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA GDDFSRRYRR DFAEMSSQLH 130 140 150 160 170 180 LTPFTARGRF ATVVEELFRD GVNWGRIVAF FEFGGVMCVE SVNREMSPLV DNIALWMTEY 190 200 210 220 230 LNRHLHTWIQ DNGGWDAFVE LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK
	Isoform Beta [UniParc]. Checksum: 2A271F901814EF69	FASTA	203	22,141
	10 20 30 40 50 60 MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS SQPGHTPHPA 70 80 90 100 110 120 ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA GDDFSRRYRR DFAEMSSQLH 130 140 150 160 170 180 LTPFTARGRF ATVVEELFRD GVNWGRIVAF FEFGGVMCVE SVNREMSPLV DNIALWMTEY 190 200 LNRHLHTWIQ DNGGWVGASG DVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma." Tsujimoto Y., Croce C.M. Proc. Natl. Acad. Sci. U.S.A. 83:5214-5218(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
[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 96; 110 AND 237.
[3]	"Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation." Cleary M.L., Smith S.D., Sklar J. Cell 47:19-28(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[4]	"Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma." Seto M., Jaeger U., Hockett R.D., Graninger W., Bennett S., Goldman P., Korsmeyer S.J. EMBO J. 7:123-131(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), VARIANT SER-7.
[5]	"Consequences of the t(14;18) chromosomal translocation in follicular lymphoma: deregulated expression of a chimeric and mutated BCL-2 gene." Hua C., Zorn S., Jensen J.P., Coupland R.W., Ko H.S., Wright J.J., Bakhshi A. Oncogene Res. 2:263-275(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT SER-7.
[6]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-43.
[7]	"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] (ISOFORM ALPHA). Tissue: Testis.
[8]	"Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas." Tanaka S., Louie D.C., Kant J.A., Reed J.C. Blood 79:229-237(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-131 (ISOFORM ALPHA), VARIANTS NON-HODGKIN LYMPHOMA SER-59 AND ILE-93.
[9]	"Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death." Hockenbery D., Nunez G., Milliman C., Schreiber R.D., Korsmeyer S.J. Nature 348:334-336(1990) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax." Yin X.-M., Oltvai Z.N., Korsmeyer S.J. Nature 369:321-323(1994) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[11]	"BAG-1 modulates the chaperone activity of Hsp70/Hsc70." Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C., Aime-Sempe C., Xie Z., Morimoto R.I., Reed J.C. EMBO J. 16:4887-4896(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BAG1.
[12]	"Conversion of Bcl-2 to a Bax-like death effector by caspases." Cheng E.H.-Y., Kirsch D.G., Clem R.J., Ravi R., Kastan M.B., Bedi A., Ueno K., Hardwick J.M. Science 278:1966-1968(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE BY CASPASES, MUTAGENESIS.
[13]	"The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell cycle progression at G2/M." Naumovski L., Cleary M.L. Mol. Cell. Biol. 16:3884-3892(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TP53BP2.
[14]	"Phosphorylation of Bcl2 and regulation of apoptosis." Ruvolo P.P., Deng X., May W.S. Leukemia 15:515-522(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON PHOSPHORYLATION.
[15]	"BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M." Yamamoto K., Ichijo H., Korsmeyer S.J. Mol. Cell. Biol. 19:8469-8478(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY ASK1/JNK1.
[16]	"PUMA induces the rapid apoptosis of colorectal cancer cells." Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B. Mol. Cell 7:673-682(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BBC3 AND BCL2L1.
[17]	"BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis." Qin W., Hu J., Guo M., Xu J., Li J., Yao G., Zhou X., Jiang H., Zhang P., Shen L., Wan D., Gu J. Biochem. Biophys. Res. Commun. 308:379-385(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BNIPL.
[18]	"The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38)." Kang C.B., Tai J., Chia J., Yoon H.S. FEBS Lett. 579:1469-1476(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FKBP8.
[19]	"p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association." Jin S., Zhuo Y., Guo W., Field J. J. Biol. Chem. 280:24698-24705(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAF1.
[20]	"BMRP is a Bcl-2 binding protein that induces apoptosis." Chintharlapalli S.R., Jasti M., Malladi S., Parsa K.V.L., Ballestero R.P., Gonzalez-Garcia M. J. Cell. Biochem. 94:611-626(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MRPL41.
[21]	"Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression." Portier B.P., Taglialatela G. J. Biol. Chem. 281:40493-40502(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FKBP8.
[22]	"JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy." Wei Y., Pattingre S., Sinha S., Bassik M., Levine B. Mol. Cell 30:678-688(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-69; SER-70 AND SER-87 BY MAPK8/JNK1, FUNCTION.
[23]	"Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2." Welch C., Santra M.K., El-Assaad W., Zhu X., Huber W.E., Keys R.A., Teodoro J.G., Green M.R. Cancer Res. 69:6782-6789(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH G0S2.
[24]	"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.
[25]	"Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells." Liu Y., Huo Z., Yan B., Lin X., Zhou Z.N., Liang X., Zhu W., Liang D., Li L., Liu Y., Zhao H., Sun Y., Chen Y.H. Biochem. Biophys. Res. Commun. 401:231-237(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EGLN3.
[26]	"Parkin mono-ubiquitinates Bcl-2 and regulates autophagy." Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G. J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY PARK2.
[27]	"Human Bop is a novel BH3-only member of the Bcl-2 protein family." Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L., Tang H. Protein Cell 3:790-801(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BOP/C22ORF29.
[28]	"Solution structure of the antiapoptotic protein bcl-2." Petros A.M., Medek A., Nettesheim D.G., Kim D.H., Yoon H.S., Swift K., Matayoshi E.D., Oltersdorf T., Fesik S.W. Proc. Natl. Acad. Sci. U.S.A. 98:3012-3017(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-207.
[29]	"An inhibitor of Bcl-2 family proteins induces regression of solid tumours." Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C., Augeri D.J., Belli B.A., Bruncko M., Deckwerth T.L., Dinges J., Hajduk P.J., Joseph M.K., Kitada S., Korsmeyer S.J., Kunzer A.R., Letai A., Li C., Mitten M.J., Nettesheim D.G. , Ng S.-C., Nimmer P.M., O'Connor J.M., Oleksijew A., Petros A.M., Reed J.C., Shen W., Tahir S.K., Thompson C.B., Tomaselli K.J., Wang B., Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H. Nature 435:677-681(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 45-207.
[30]	"Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL." Bruncko M., Oost T.K., Belli B.A., Ding H., Joseph M.K., Kunzer A., Martineau D., McClellan W.J., Mitten M., Ng S.-C., Nimmer P.M., Oltersdorf T., Park C.-M., Petros A.M., Shoemaker A.R., Song X., Wang X., Wendt M.D. , Zhang H., Fesik S.W., Rosenberg S.H., Elmore S.W. J. Med. Chem. 50:641-662(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 44-207.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

Bcl-2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13994 mRNA. Translation: AAA51813.1. Sequence problems.
M13995 mRNA. Translation: AAA51814.1. Sequence problems.
M14745 mRNA. Translation: AAA35591.1.
X06487 mRNA. Translation: CAA29778.1.
AY220759 Genomic DNA. Translation: AAO26045.1.
BC027258 mRNA. Translation: AAH27258.1.
S72602 Genomic DNA. Translation: AAD14111.1. Sequence problems.

IPI

IPI00020961.
IPI00217817.

PIR

TVHUB1. B29409.
TVHUA1. C37332.

RefSeq

NP_000624.2. NM_000633.2.

UniGene

Hs.150749.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G5M	NMR	-	A	1-207	[»]
1GJH	NMR	-	A	1-207	[»]
1YSW	NMR	-	A	3-207	[»]
2O21	NMR	-	A	3-207	[»]
2O22	NMR	-	A	3-207	[»]
2O2F	NMR	-	A	8-204	[»]
2W3L	X-ray	2.10	A/B	9-206	[»]
2XA0	X-ray	2.70	A/B	1-207	[»]
4AQ3	X-ray	2.40	A/B/C/D/E/F	1-207	[»]

DisProt

DP00297.

ProteinModelPortal

P10415.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1043N.

IntAct

P10415. 33 interactions.

MINT

MINT-87089.

STRING

9606.ENSP00000329623.

PTM databases

PhosphoSite

P10415.

Polymorphism databases

DMDM

231632.

Proteomic databases

PaxDb

P10415.

PRIDE

P10415.

Protocols and materials databases

DNASU

596.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000333681; ENSP00000329623; ENSG00000171791.
ENST00000398117; ENSP00000381185; ENSG00000171791.

GeneID

596.

KEGG

hsa:596.

UCSC

uc002lit.1. human.

Organism-specific databases

CTD

596.

GeneCards

GC18M060763.

HGNC

HGNC:990. BCL2.

HPA

CAB000003.

MIM

151430. gene+phenotype.

neXtProt

NX_P10415.

Orphanet

544. Diffuse large B-cell lymphoma.
545. Follicular lymphoma.

PharmGKB

PA25302.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG275924.

HOGENOM

HOG000056452.

HOVERGEN

HBG004472.

InParanoid

P10415.

KO

K02161.

OMA

EWDAGDA.

OrthoDB

EOG4X97J4.

PhylomeDB

P10415.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
ceramidepathway. Ceramide signaling pathway.
epopathway. EPO signaling pathway.
faspathway. FAS signaling pathway (CD95).
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
rxr_vdr_pathway. RXR and RAR hetrodimerization with other nuclear receptor.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_578. Apoptosis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P10415.

Bgee

P10415.

CleanEx

HS_BCL2.

Genevestigator

P10415.

GermOnline

ENSG00000171791. Homo sapiens.

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

BindingDB

P10415.

ChEMBL

CHEMBL4860.

DrugBank

DB01248. Docetaxel.
DB01073. Fludarabine.
DB01065. Melatonin.
DB01229. Paclitaxel.
DB01367. Rasagiline.

EvolutionaryTrace

P10415.

GenomeRNAi

596.

NextBio

2423.

PMAP-CutDB

P10415.

SOURCE

Search...

Entry information

Entry name

BCL2_HUMAN

Accession

Primary (citable) accession number: P10415
Secondary accession number(s): P10416, Q13842, Q16197

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 176 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.