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P10415 (BCL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 190. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptosis regulator Bcl-2
Gene names
Name:BCL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length239 AA.
Sequence statusComplete.
Protein existenceEvidence 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.24

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. Interacts with the SCF(FBXO10) complex. Ref.13 Ref.15 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.29 Ref.30

Subcellular location

Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein Ref.11.

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.17 Ref.24

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.14

Monoubiquitinated by PARK2, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome. Ref.28 Ref.30

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 processApoptosis
   Cellular componentEndoplasmic reticulum
Membrane
Mitochondrion
Mitochondrion outer membrane
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Proto-oncogene
   DomainTransmembrane
Transmembrane helix
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from electronic annotation. Source: Ensembl

B cell lineage commitment

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

T cell differentiation in thymus

Inferred from electronic annotation. Source: Ensembl

T cell homeostasis

Inferred from electronic annotation. Source: Ensembl

actin filament organization

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Traceable author statement. Source: Reactome

axon regeneration

Inferred from electronic annotation. Source: Ensembl

axonogenesis

Inferred from electronic annotation. Source: Ensembl

behavioral fear response

Inferred from electronic annotation. Source: Ensembl

branching involved in ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell aging

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from direct assay PubMed 36599PubMed 8022822. Source: MGI

cell growth

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

cellular response to glucose starvation

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to organic substance

Inferred from electronic annotation. Source: Ensembl

cochlear nucleus development

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from direct assay PubMed 10620603. Source: UniProtKB

developmental growth

Inferred from electronic annotation. Source: Ensembl

digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

ear development

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum calcium ion homeostasis

Traceable author statement PubMed 18309324. Source: UniProtKB

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay PubMed 10597216. Source: MGI

female pregnancy

Non-traceable author statement PubMed 11530860. Source: UniProtKB

focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

glomerulus development

Inferred from electronic annotation. Source: Ensembl

hair follicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

homeostasis of number of cells within a tissue

Inferred from electronic annotation. Source: Ensembl

humoral immune response

Traceable author statement PubMed 1908951. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from Biological aspect of Ancestor. Source: RefGenome

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from direct assay PubMed 15776018. Source: MGI

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

lymphoid progenitor cell differentiation

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from electronic annotation. Source: Ensembl

melanin metabolic process

Inferred from electronic annotation. Source: Ensembl

melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

mesenchymal cell development

Inferred from electronic annotation. Source: Ensembl

metanephros development

Inferred from electronic annotation. Source: Ensembl

negative regulation of G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of anoikis

Inferred from mutant phenotype PubMed 15006356. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 10506221PubMed 10620603PubMed 9027314. 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: Ensembl

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of cellular pH reduction

Inferred from direct assay PubMed 10506221. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from genetic interaction PubMed 8358790. Source: MGI

negative regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 11684014. 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: Ensembl

negative regulation of myeloid cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 7546744. Source: MGI

negative regulation of ossification

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of retinal cell programmed cell death

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

organ growth

Inferred from electronic annotation. Source: Ensembl

ossification

Inferred from electronic annotation. Source: Ensembl

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

pigment granule organization

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell proliferation

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

positive regulation of catalytic activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from direct assay PubMed 8022822. Source: MGI

positive regulation of intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

positive regulation of melanocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron maturation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

positive regulation of skeletal muscle fiber development

Inferred from electronic annotation. Source: Ensembl

positive regulation of smooth muscle cell migration

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

protein dephosphorylation

Inferred from electronic annotation. Source: Ensembl

protein polyubiquitination

Inferred from direct assay PubMed 16717086. Source: MGI

reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of calcium ion transport

Inferred from direct assay PubMed 8022822. Source: MGI

regulation of cell-matrix adhesion

Inferred from electronic annotation. Source: Ensembl

regulation of glycoprotein biosynthetic process

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

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 stability

Inferred from electronic annotation. Source: Ensembl

regulation of transmembrane transporter activity

Inferred from direct assay PubMed 9219694. Source: BHF-UCL

regulation of viral genome replication

Inferred from electronic annotation. Source: Ensembl

release of cytochrome c from mitochondria

Non-traceable author statement PubMed 9027314. Source: UniProtKB

renal system process

Inferred from electronic annotation. Source: Ensembl

response to UV-B

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from direct assay PubMed 9184696. Source: MGI

response to drug

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

response to gamma radiation

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to iron ion

Inferred from direct assay PubMed 11264898. Source: UniProtKB

response to ischemia

Inferred from electronic annotation. Source: Ensembl

response to nicotine

Inferred from direct assay PubMed 12421819. Source: UniProtKB

response to radiation

Non-traceable author statement PubMed 15799693. Source: UniProtKB

response to toxic substance

Inferred from direct assay PubMed 16307838. Source: HGNC

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

spleen development

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Inferred from direct assay PubMed 9219694. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11530860. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay PubMed 8402648. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from direct assay PubMed 7896880. Source: MGI

mitochondrial outer membrane

Inferred from direct assay PubMed 8402648PubMed 9027314. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 9027314. Source: UniProtKB

myelin sheath

Inferred from electronic annotation. Source: Ensembl

nuclear membrane

Inferred from direct assay PubMed 1502141PubMed 8402648PubMed 1502141PubMed 1502141. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 7546744PubMed 7896880. Source: MGI

pore complex

Inferred from direct assay PubMed 9219694. Source: BHF-UCL

   Molecular_functionBH3 domain binding

Inferred from physical interaction PubMed 9111042. Source: UniProtKB

channel activity

Inferred from direct assay PubMed 9219694. Source: BHF-UCL

channel inhibitor activity

Inferred from direct assay PubMed 9219694. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 18835031PubMed 9463381. Source: IntAct

protease binding

Inferred from direct assay PubMed 10620603. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 21454712. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 9111042. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 9111042. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 12086670. Source: MGI

ubiquitin protein ligase binding

Inferred from physical interaction Ref.28. Source: UniProtKB

Complete GO annotation...

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 → VGALGDVSLG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 239239Apoptosis regulator Bcl-2
PRO_0000143048

Regions

Transmembrane212 – 23322Helical; Potential
Motif10 – 3021BH4
Motif93 – 10715BH3
Motif136 – 15520BH1
Motif187 – 20216BH2

Sites

Site34 – 352Cleavage; by caspase-3

Amino acid modifications

Modified residue691Phosphothreonine; by MAPK8 Ref.24
Modified residue701Phosphoserine; by MAPK8 and PKC Ref.24
Modified residue871Phosphoserine; by MAPK8 Ref.24

Natural variations

Alternative sequence196 – 23944DAFVE…YLGHK → VGALGDVSLG in isoform Beta.
VSP_000512
Natural variant71T → S. Ref.4 Ref.5
VAR_000827
Natural variant431A → T. Ref.6
Corresponds to variant rs1800477 [ dbSNP | Ensembl ].
VAR_014716
Natural variant591P → S in non-Hodgkin lymphoma; somatic mutation. Ref.10
VAR_000828
Natural variant931V → I in non-Hodgkin lymphoma; somatic mutation. Ref.10
VAR_000829

Experimental info

Mutagenesis341D → A: Abolishes cleavage by caspase-3.
Mutagenesis641D → A: No effect on cleavage by caspase-3.
Mutagenesis1451G → A: No heterodimerization with BAX and loss of anti-apoptotic activity.
Mutagenesis1881W → A: No heterodimerization with BAX and loss of anti-apoptotic activity.
Sequence conflict481I → F in CAA29778. Ref.4
Sequence conflict591P → T in AAA35591. Ref.3
Sequence conflict961T → A in AAD14111. Ref.10
Sequence conflict1101R → G in AAD14111. Ref.10
Sequence conflict1171S → R in AAA35591. Ref.3
Sequence conflict1291R → C in CAA29778. Ref.4
Isoform Beta:
Sequence conflict1991L → S in AAA51814. Ref.1

Secondary structure

...................... 239
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified April 1, 1993. Version 2.
Checksum: 3C49F2B714DC9CCB

FASTA23926,266
        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 

« Hide

Isoform Beta [UniParc].

Checksum: E3B15A271F900A84
Show »

FASTA20522,337

References

« Hide '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]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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.
[24]"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.
[25]"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.
[26]"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.
[27]"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.
[28]"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.
[29]"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.
[30]"Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma."
Chiorazzi M., Rui L., Yang Y., Ceribelli M., Tishbi N., Maurer C.W., Ranuncolo S.M., Zhao H., Xu W., Chan W.C., Jaffe E.S., Gascoyne R.D., Campo E., Rosenwald A., Ott G., Delabie J., Rimsza L.M., Shaham S., Staudt L.M.
Proc. Natl. Acad. Sci. U.S.A. 110:3943-3948(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FBXO10, UBIQUITINATION, IDENTIFICATION IN THE SCF(FBXO10) COMPLEX.
[31]"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.
[32]"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. expand/collapse author list , 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.
[33]"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. expand/collapse author list , 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.

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.
AC021803 Genomic DNA. No translation available.
AC022726 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW63137.1.
BC027258 mRNA. Translation: AAH27258.1.
S72602 Genomic DNA. Translation: AAD14111.1. Sequence problems.
CCDSCCDS11981.1. [P10415-1]
PIRTVHUB1. B29409.
TVHUA1. C37332.
RefSeqNP_000624.2. NM_000633.2. [P10415-1]
NP_000648.2. NM_000657.2. [P10415-2]
UniGeneHs.150749.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G5MNMR-A1-34[»]
A92-207[»]
1GJHNMR-A1-34[»]
A92-207[»]
1YSWNMR-A3-33[»]
A92-206[»]
2O21NMR-A3-34[»]
A92-207[»]
2O22NMR-A3-34[»]
A92-207[»]
2O2FNMR-A8-31[»]
A92-204[»]
2W3LX-ray2.10A/B92-206[»]
2XA0X-ray2.70A/B1-207[»]
4AQ3X-ray2.40A/B/C/D/E/F1-33[»]
A/B/C/D/E/F92-207[»]
4IEHX-ray2.10A1-34[»]
A92-207[»]
4LVTX-ray2.05A/B1-34[»]
A/B92-207[»]
4LXDX-ray1.90A1-34[»]
A92-207[»]
4MANX-ray2.07A/B1-34[»]
A/B92-207[»]
DisProtDP00297.
ProteinModelPortalP10415.
SMRP10415. Positions 3-207.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107068. 90 interactions.
DIPDIP-1043N.
IntActP10415. 45 interactions.
MINTMINT-87089.
STRING9606.ENSP00000329623.

Chemistry

BindingDBP10415.
ChEMBLCHEMBL4860.
DrugBankDB01248. Docetaxel.
DB01073. Fludarabine.
DB01065. Melatonin.
DB01229. Paclitaxel.
DB01367. Rasagiline.

PTM databases

PhosphoSiteP10415.

Polymorphism databases

DMDM231632.

Proteomic databases

MaxQBP10415.
PaxDbP10415.
PRIDEP10415.

Protocols and materials databases

DNASU596.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000333681; ENSP00000329623; ENSG00000171791. [P10415-1]
ENST00000398117; ENSP00000381185; ENSG00000171791. [P10415-1]
ENST00000444484; ENSP00000404214; ENSG00000171791.
ENST00000589955; ENSP00000466417; ENSG00000171791.
GeneID596.
KEGGhsa:596.
UCSCuc002lit.1. human. [P10415-1]

Organism-specific databases

CTD596.
GeneCardsGC18M060763.
HGNCHGNC:990. BCL2.
HPACAB000003.
MIM151430. gene+phenotype.
neXtProtNX_P10415.
Orphanet545. Follicular lymphoma.
98839. Intravascular large B-cell lymphoma.
PharmGKBPA25302.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG275924.
HOGENOMHOG000056452.
HOVERGENHBG004472.
InParanoidP10415.
KOK02161.
OMAIVLKYIH.
OrthoDBEOG70GMGD.
PhylomeDBP10415.
TreeFamTF315834.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP10415.
BgeeP10415.
CleanExHS_BCL2.
GenevestigatorP10415.

Family and domain databases

InterProIPR013278. 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]
PANTHERPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsTIGR00865. bcl-2. 1 hit.
PROSITEPS50062. 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]
ProtoNetSearch...

Other

EvolutionaryTraceP10415.
GeneWikiBcl-2.
GenomeRNAi596.
NextBio2423.
PMAP-CutDBP10415.
PROP10415.
SOURCESearch...

Entry information

Entry nameBCL2_HUMAN
AccessionPrimary (citable) accession number: P10415
Secondary accession number(s): C9JHD5 expand/collapse secondary AC list , P10416, Q13842, Q16197
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1993
Last modified: July 9, 2014
This is version 190 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM