Tag Content
SG ID
SG00000612 
UniProt Accession
Theoretical PI
6.75  
Molecular Weight
26266 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
BCL2 
Gene Synonyms/Alias
 
Protein Name
Apoptosis regulator Bcl-2 
Protein Synonyms/Alias
 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:18;60790579-60987361;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr variant is associated with protection against azoospermia in the Han-Chinese population. 
The information of related literatures
1. J. Ma, H. Y. Lu, Y. K. Xia, H. B. Dong, A. H. Gu, Z. Y. Li, Z. Li, A. M. Chen, X. R. Wang and S. L. Wang (2010) BCL2 Ala43Thr is a functional variant associated with protection against azoospermia in a Han-Chinese population. Biol Reprod 83(4): 656-62. 

Abstract
Apoptosis is very common during various stages of mammalian germ cell development and differentiation, and the BCL2 gene is one of the most important apoptotic regulators. Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis. In the present study, single nucleotide polymorphisms (SNPs) in coding regions of the BCL2 gene were examined in a hospital-based, case-control study including 198 infertile patients with idiopathic azoospermia and 183 fertile controls. Subsequently, a functional study was conducted for comparison of paclitaxel-induced cytotoxicity and apoptosis between the BCL2 variant and the wild type in vitro. Three SNPs were found in exon 2--A21G (rs1801018), G127A (rs1800477), and C300T (rs61733416)--with the latter first reported in the Han-Chinese population. The frequency of G127A (GA+AA) genotype was significantly lower in azoospermic, infertile men compared to the age-matched controls (P = 0.01). This genotype may confer a lower risk of azoospermia (adjusted odd ratio [OR] = 0.448, 95% confidence interval = 0.226-0.889). In addition, HeLa cells expressing the BCL2 Ala43Thr (G127A), similar to the control cells, were more sensitive to paclitaxel-induced cytotoxicity and apoptosis than those expressing wild-type BCL2. Consistently, the cleaved PARP and p-BCL2 proteins were subsequently increased after paclitaxel treatment, as also predicted by the bioinformatics analysis. Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr variant is associated with protection against azoospermia in the Han-Chinese population. PMID: [20610805] 

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Figures for illustrating the function of this protein/gene
Function
Suppresses apoptosis in a variety of cell systemsincluding factor-dependent lymphohematopoietic and neural cells.Regulates cell death by controlling the mitochondrial membranepermeability. Appears to function in a feedback loop system withcaspases. Inhibits caspase activity either by preventing therelease of cytochrome c from the mitochondria and/or by binding tothe apoptosis-activating factor (APAF-1). 
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Subcellular Location
Mitochondrion outer membrane; Single-passmembrane protein. Nucleus membrane; Single-pass membrane protein.Endoplasmic reticulum membrane; Single-pass membrane protein. 
Tissue Specificity
Expressed in a variety of tissues. 
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol IEA:Compara.
GO:0005783 C:endoplasmic reticulum IDA:UniProtKB.
GO:0005789 C:endoplasmic reticulum membrane IEA:UniProtKB-SubCell.
GO:0005792 C:microsome IEA:Compara.
GO:0005741 C:mitochondrial outer membrane IDA:UniProtKB.
GO:0043209 C:myelin sheath IEA:Compara.
GO:0031965 C:nuclear membrane IDA:UniProtKB.
GO:0046930 C:pore complex IDA:BHF-UCL.
GO:0015267 F:channel activity IDA:BHF-UCL.
GO:0043565 F:sequence-specific DNA binding IDA:MGI.
GO:0007015 P:actin filament organization IEA:Compara.
GO:0008633 P:activation of pro-apoptotic gene products TAS:Reactome.
GO:0006916 P:anti-apoptosis IDA:UniProtKB.
GO:0031103 P:axon regeneration IEA:Compara.
GO:0001782 P:B cell homeostasis IEA:Compara.
GO:0002326 P:B cell lineage commitment IEA:Compara.
GO:0042100 P:B cell proliferation IDA:MGI.
GO:0050853 P:B cell receptor signaling pathway IMP:UniProtKB.
GO:0001662 P:behavioral fear response IEA:Compara.
GO:0001658 P:branching involved in ureteric bud morphogenesis IEA:Compara.
GO:0043375 P:CD8-positive, alpha-beta T cell lineage commitment IEA:Compara.
GO:0007569 P:cell aging IEA:Compara.
GO:0016049 P:cell growth IEA:Compara.
GO:0016337 P:cell-cell adhesion IEA:Compara.
GO:0071310 P:cellular response to organic substance IEA:Compara.
GO:0021747 P:cochlear nucleus development IEA:Compara.
GO:0051607 P:defense response to virus IDA:UniProtKB.
GO:0048589 P:developmental growth IEA:Compara.
GO:0048546 P:digestive tract morphogenesis IEA:Compara.
GO:0043583 P:ear development IEA:Compara.
GO:0032469 P:endoplasmic reticulum calcium ion homeostasis IEA:Compara.
GO:0007565 P:female pregnancy NAS:UniProtKB.
GO:0048041 P:focal adhesion assembly IEA:Compara.
GO:0000082 P:G1/S transition of mitotic cell cycle IEA:Compara.
GO:0022612 P:gland morphogenesis IEA:Compara.
GO:0034349 P:glial cell apoptotic process IEA:Compara.
GO:0032835 P:glomerulus development IEA:Compara.
GO:0048873 P:homeostasis of number of cells within a tissue IEA:Compara.
GO:0006959 P:humoral immune response TAS:UniProtKB.
GO:0008629 P:induction of apoptosis by intracellular signals TAS:Reactome.
GO:0045087 P:innate immune response TAS:Reactome.
GO:0070059 P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IDA:MGI.
GO:0002320 P:lymphoid progenitor cell differentiation IEA:Compara.
GO:0008584 P:male gonad development IEA:Compara.
GO:0006582 P:melanin metabolic process IEA:Compara.
GO:0030318 P:melanocyte differentiation IEA:Compara.
GO:0014031 P:mesenchymal cell development IEA:Compara.
GO:0001656 P:metanephros development IEA:Compara.
GO:2001234 P:negative regulation of apoptotic signaling pathway IMP:UniProtKB.
GO:0010523 P:negative regulation of calcium ion transport into cytosol IEA:Compara.
GO:0030308 P:negative regulation of cell growth IEA:Compara.
GO:0030336 P:negative regulation of cell migration IEA:Compara.
GO:0032848 P:negative regulation of cellular pH reduction IDA:UniProtKB.
GO:0051902 P:negative regulation of mitochondrial depolarization TAS:UniProtKB.
GO:0045930 P:negative regulation of mitotic cell cycle IEA:Compara.
GO:0033033 P:negative regulation of myeloid cell apoptotic process IEA:Compara.
GO:0043524 P:negative regulation of neuron apoptotic process IDA:MGI.
GO:0030279 P:negative regulation of ossification IEA:Compara.
GO:0033689 P:negative regulation of osteoblast proliferation IEA:Compara.
GO:0046671 P:negative regulation of retinal cell programmed cell death IEA:Compara.
GO:0051402 P:neuron apoptotic process TAS:HGNC.
GO:0035872 P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway TAS:Reactome.
GO:0048709 P:oligodendrocyte differentiation IEA:Compara.
GO:0048599 P:oocyte development IEA:Compara.
GO:0035265 P:organ growth IEA:Compara.
GO:0009887 P:organ morphogenesis IEA:Compara.
GO:0001503 P:ossification IEA:Compara.
GO:0001541 P:ovarian follicle development IEA:Compara.
GO:0018105 P:peptidyl-serine phosphorylation IEA:Compara.
GO:0018107 P:peptidyl-threonine phosphorylation IEA:Compara.
GO:0048753 P:pigment granule organization IEA:Compara.
GO:0030890 P:positive regulation of B cell proliferation IMP:UniProtKB.
GO:0043085 P:positive regulation of catalytic activity IEA:Compara.
GO:0030307 P:positive regulation of cell growth IDA:MGI.
GO:0045636 P:positive regulation of melanocyte differentiation IEA:Compara.
GO:0040018 P:positive regulation of multicellular organism growth IEA:Compara.
GO:0014042 P:positive regulation of neuron maturation IEA:Compara.
GO:0033138 P:positive regulation of peptidyl-serine phosphorylation IEA:Compara.
GO:0048743 P:positive regulation of skeletal muscle fiber development IEA:Compara.
GO:0014911 P:positive regulation of smooth muscle cell migration IEA:Compara.
GO:0009791 P:post-embryonic development IEA:Compara.
GO:0006470 P:protein dephosphorylation IEA:Compara.
GO:0000209 P:protein polyubiquitination IDA:MGI.
GO:0072593 P:reactive oxygen species metabolic process IEA:Compara.
GO:0051924 P:regulation of calcium ion transport IDA:MGI.
GO:0001952 P:regulation of cell-matrix adhesion IEA:Compara.
GO:0010559 P:regulation of glycoprotein biosynthetic process IEA:Compara.
GO:0046902 P:regulation of mitochondrial membrane permeability ISS:HGNC.
GO:0051881 P:regulation of mitochondrial membrane potential ISS:HGNC.
GO:0006808 P:regulation of nitrogen utilization IEA:Compara.
GO:0043497 P:regulation of protein heterodimerization activity IDA:UniProtKB.
GO:0043496 P:regulation of protein homodimerization activity IDA:UniProtKB.
GO:0032880 P:regulation of protein localization IEA:Compara.
GO:0031647 P:regulation of protein stability IEA:Compara.
GO:0022898 P:regulation of transmembrane transporter activity IDA:BHF-UCL.
GO:0001836 P:release of cytochrome c from mitochondria NAS:UniProtKB.
GO:0003014 P:renal system process IEA:Compara.
GO:0010044 P:response to aluminum ion IEA:Compara.
GO:0031000 P:response to caffeine IEA:Compara.
GO:0046688 P:response to copper ion IEA:Compara.
GO:0051412 P:response to corticosterone stimulus IEA:Compara.
GO:0034097 P:response to cytokine stimulus IDA:MGI.
GO:0006974 P:response to DNA damage stimulus IMP:UniProtKB.
GO:0042493 P:response to drug IMP:UniProtKB.
GO:0043627 P:response to estrogen stimulus IEA:Compara.
GO:0045471 P:response to ethanol IEA:Compara.
GO:0051593 P:response to folic acid IEA:Compara.
GO:0010332 P:response to gamma radiation IEA:Compara.
GO:0009408 P:response to heat IEA:Compara.
GO:0042542 P:response to hydrogen peroxide IEA:Compara.
GO:0001666 P:response to hypoxia IEA:Compara.
GO:0032868 P:response to insulin stimulus IEA:Compara.
GO:0010039 P:response to iron ion IDA:UniProtKB.
GO:0033591 P:response to L-ascorbic acid IEA:Compara.
GO:0035094 P:response to nicotine IDA:UniProtKB.
GO:0009314 P:response to radiation NAS:UniProtKB.
GO:0009636 P:response to toxin IDA:HGNC.
GO:0010224 P:response to UV-B IEA:Compara.
GO:0048536 P:spleen development IEA:Compara.
GO:0033077 P:T cell differentiation in thymus IEA:Compara.
GO:0043029 P:T cell homeostasis IEA:Compara.
GO:0048538 P:thymus development IEA:Compara.
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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.
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Pfam
PF00452;    Bcl-2;    1.
PF02180;    BH4;    1.
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SMART
SM00265;    BH4;    1.
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PROSITE
PS50062;    BCL2_FAMILY;    1.
PS01080;    BH1;    1.
PS01258;    BH2;    1.
PS01259;    BH3;    1.
PS01260;    BH4_1;    1.
PS50063;    BH4_2;    1.
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PRINTS
PR01863;    APOPREGBCL2.;   
PR01862;    BCL2FAMILY.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    239       Apoptosis regulator Bcl-2.
                             /FTId=PRO_0000143048.
TRANSMEM    212    233       Helical; (Potential).
MOTIF        10     30       BH4.
MOTIF        93    107       BH3.
MOTIF       136    155       BH1.
MOTIF       187    202       BH2.
SITE         34     35       Cleavage; by caspase-3.
MOD_RES      69     69       Phosphothreonine; by MAPK8.
MOD_RES      70     70       Phosphoserine; by MAPK8 and PKC.
MOD_RES      87     87       Phosphoserine; by MAPK8.
VAR_SEQ     196    239       DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYL
                             GHK -> VGASGDVS (in isoform Beta).
                             /FTId=VSP_000512.
VARIANT       7      7       T -> S.
                             /FTId=VAR_000827.
VARIANT      43     43       A -> T (in dbSNP:rs1800477).
                             /FTId=VAR_014716.
VARIANT      59     59       P -> S (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_000828.
VARIANT      93     93       V -> I (in non-Hodgkin lymphoma; somatic
                             mutation).
                             /FTId=VAR_000829.
MUTAGEN      34     34       D->A: Abolishes cleavage by caspase-3.
MUTAGEN      64     64       D->A: No effect on cleavage by caspase-3.
MUTAGEN     145    145       G->A: No heterodimerization with BAX and
                             loss of anti-apoptotic activity.
MUTAGEN     188    188       W->A: No heterodimerization with BAX and
                             loss of anti-apoptotic activity.
CONFLICT     48     48       I -> F (in Ref. 4; CAA29778).
CONFLICT     59     59       P -> T (in Ref. 3; AAA35591).
CONFLICT     96     96       T -> A (in Ref. 8; AAD14111).
CONFLICT    110    110       R -> G (in Ref. 8; AAD14111).
CONFLICT    117    117       S -> R (in Ref. 3; AAA35591).
CONFLICT    129    129       R -> C (in Ref. 4; CAA29778).
HELIX        11     25
TURN         32     34
HELIX        92    107
HELIX       109    116
TURN        123    125
HELIX       126    137
TURN        138    140
HELIX       144    163
HELIX       169    184
HELIX       186    191
HELIX       195    201
HELIX       203    205
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Nucleotide Sequence
Length: 5086 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 239 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
Gene Symbol Ref Databases
PPP2R5AHPRD 
BIDBioGRID 
HSPA1ABioGRID 
ADIPOQString 
ADIPOR1String 
PMAIP1HPRD 
TP53BP2HPRD 
AVENBioGRID 
BCL2L1HPRD 
BCL2L10HPRD 
BCL2L11HPRD 
Bcl2l11BioGRID 
BCL2L14HPRD 
_HPRD 
BIDBioGRID 
BCAP31HPRD 
_HPRD 
_BioGRID 
PPP2CAHPRD 
_HPRD 
NR4A1BioGRID 
_BioGRID 
PRKCAHPRD 
_BioGRID 
BADHPRD 
BadIntAct 
BAG1BioGRID 
BAG3HPRD 
BAG4HPRD 
BAK1HPRD 
BCAP31BioGRID 
BAXHPRD 
BaxIntAct 
BBC3HPRD 
PPP2R5ABioGRID 
BIDBioGRID 
HSPA1AHPRD 
PPP3CAHPRD 
ADIPOQString 
ADIPOR1String 
PMAIP1BioGRID 
TP53BP2MINT 
ATP2A2HPRD 
BCL2L1BioGRID 
BCL2L11BioGRID 
Bcl2l11BioGRID 
BIDBioGRID 
_BioGRID 
_HPRD 
PPP2CABioGRID 
_BioGRID 
_BioGRID 
NR4A1BioGRID 
_BioGRID 
_BioGRID 
BADIntAct 
BAK1BioGRID 
BAXBioGRID 
BaxMINT 
BBC3BioGRID 
BCL2HPRD 
BCL2HPRD 
BECN1BioGRID 
TMBIM6HPRD 
BIDBioGRID 
BIKBioGRID 
BMFBioGRID 
BNIP3LBioGRID 
BNIP2BioGRID 
BNIP3BioGRID 
BNIPLBioGRID 
PPP3R1MINT 
CASP8BioGRID 
CDK1BioGRID 
CDK2HPRD 
CYCSHPRD 
Dynlrb2IntAct 
DYNLL1BioGRID 
BBC3BioGRID 
ITPR1BioGRID 
FKBP8BioGRID 
HRKBioGRID 
HSPA1AHPRD 
IRS1BioGRID 
IRS2BioGRID 
ITPR1BioGRID 
Itpr1DIP 
PRKACAHPRD 
MDM4MINT 
MAPK1MINT 
MAPK3HPRD 
MAPK14HPRD 
MYCHPRD 
NLRP1IntAct 
NR4A1HPRD 
BCL2L11IntAct 
Bcl2l11IntAct 
PXNHPRD 
POLDIP3String 
PIN1BioGRID 
PMLHPRD 
gag-polBioGRID 
PPP1CAIntAct 
PPP2CABioGRID 
PPP3CAHPRD 
PSEN1HPRD 
Bcl2l11BioGRID 
NR4A1HPRD 
Bcl2l11BioGRID 
_BioGRID 
BCL2L1BioGRID 
DNCL1BioGRID 
BNIP3LBioGRID 
polBioGRID 
RTN4BioGRID 
RTN4BioGRID 
RTN4BioGRID 
SERPINB8BioGRID 
_BioGRID 
BBC3BioGRID 
Becn1BioGRID 
_BioGRID 
RAD9ABioGRID 
RAF1BioGRID 
RRASBioGRID 
RTN4BioGRID 
SMN1BioGRID 
SOD1HPRD 
SERPINB8BioGRID 
SPNS1IntAct 
UBCBioGRID 
VRK2IntAct 
BCLAF1HPRD 
BECN1HPRD 
BFARHPRD 
TMBIM6BioGRID 
BIDHPRD 
BIKHPRD 
BLIDBioGRID 
BLKHPRD 
BMFHPRD 
BmfIntAct 
BNIP3LHPRD 
BNIP2HPRD 
BNIP3HPRD 
BNIPLHPRD 
CAPN2BioGRID 
PPP3R1MINT 
CASP2BioGRID 
CASP3HPRD 
CASP8HPRD 
CPT1AHPRD 
BBC3HPRD 
CASP2BioGRID 
EPHB2BioGRID 
FKBP8HPRD 
HRKHPRD 
HSPA1ABioGRID 
MT-RNR2MINT 
IRS1BioGRID 
ITM2BHPRD 
PRKCAHPRD 
MCL1DIP 
MDM4MINT 
MAPK1HPRD 
MAPK8HPRD 
MAPK11HPRD 
MOAP1HPRD 
NAF1MINT 
NLRP1HPRD 
NMT2HPRD 
NR4A1BioGRID 
_IntAct 
BCL2L11IntAct 
Bcl2l11IntAct 
_IntAct 
TP53HPRD 
PARP1HPRD 
POLDIP3String 
PIN1HPRD 
PKMYT1HPRD 
PPP1CAHPRD 
PPP1CBIntAct 
PPP2CAHPRD 
PSEN1BioGRID 
PPP2R4BioGRID 
BLKHPRD 
_HPRD 
_IntAct 
PKMYT1HPRD 
MAPK1HPRD 
Bcl2l11BioGRID 
MAPK1HPRD 
_HPRD 
NR4A1BioGRID 
Bcl2l11BioGRID 
_BioGRID 
BCL2L1BioGRID 
NRASHPRD 
ITM2BHPRD 
BADHPRD 
BNIP3LHPRD 
rbsB5IntAct 
RTN4BioGRID 
RTN4BioGRID 
PRKCAHPRD 
RTN4HPRD 
_HPRD 
CPT1AHPRD 
BLKHPRD 
BBC3BioGRID 
HRASHPRD 
_IntAct 
BBC3IntAct 
CASP2BioGRID 
RAD9AHPRD 
RAF1HPRD 
HRASHPRD 
KRASHPRD 
NRASHPRD 
RRASHPRD 
RTN4HPRD 
BNIP1HPRD 
SF1HPRD 
SIVA1IntAct 
SMN1HPRD 
SOD1BioGRID 
SPNS1HPRD 
TOMM20HPRD 
TP53AIP1HPRD 
VDAC1DIP 
Other Protein-Protein interaction resources
String database  
View Microarray data
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