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P10415

- BCL2_HUMAN

UniProt

P10415 - BCL2_HUMAN

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Protein

Apoptosis regulator Bcl-2

Gene

BCL2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei34 – 352Cleavage; by caspase-3

GO - Molecular functioni

  1. BH3 domain binding Source: UniProtKB
  2. channel activity Source: BHF-UCL
  3. channel inhibitor activity Source: BHF-UCL
  4. identical protein binding Source: IntAct
  5. protease binding Source: UniProtKB
  6. protein heterodimerization activity Source: UniProtKB
  7. protein homodimerization activity Source: UniProtKB
  8. sequence-specific DNA binding Source: MGI
  9. ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  1. actin filament organization Source: Ensembl
  2. apoptotic process Source: MGI
  3. axonogenesis Source: Ensembl
  4. axon regeneration Source: Ensembl
  5. B cell homeostasis Source: Ensembl
  6. B cell lineage commitment Source: Ensembl
  7. B cell proliferation Source: MGI
  8. B cell receptor signaling pathway Source: UniProtKB
  9. behavioral fear response Source: Ensembl
  10. branching involved in ureteric bud morphogenesis Source: Ensembl
  11. CD8-positive, alpha-beta T cell lineage commitment Source: Ensembl
  12. cell aging Source: Ensembl
  13. cell growth Source: Ensembl
  14. cellular response to DNA damage stimulus Source: UniProtKB
  15. cellular response to glucose starvation Source: Ensembl
  16. cellular response to hypoxia Source: Ensembl
  17. cellular response to organic substance Source: Ensembl
  18. cochlear nucleus development Source: Ensembl
  19. defense response to virus Source: UniProtKB
  20. developmental growth Source: Ensembl
  21. digestive tract morphogenesis Source: Ensembl
  22. ear development Source: Ensembl
  23. endoplasmic reticulum calcium ion homeostasis Source: UniProtKB
  24. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  25. extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  26. female pregnancy Source: UniProtKB
  27. focal adhesion assembly Source: Ensembl
  28. gland morphogenesis Source: Ensembl
  29. glomerulus development Source: Ensembl
  30. hair follicle morphogenesis Source: Ensembl
  31. homeostasis of number of cells within a tissue Source: Ensembl
  32. humoral immune response Source: UniProtKB
  33. innate immune response Source: Reactome
  34. intrinsic apoptotic signaling pathway Source: Reactome
  35. intrinsic apoptotic signaling pathway in response to DNA damage Source: RefGenome
  36. intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGI
  37. intrinsic apoptotic signaling pathway in response to oxidative stress Source: Ensembl
  38. lymphoid progenitor cell differentiation Source: Ensembl
  39. male gonad development Source: Ensembl
  40. melanin metabolic process Source: Ensembl
  41. melanocyte differentiation Source: Ensembl
  42. mesenchymal cell development Source: Ensembl
  43. metanephros development Source: Ensembl
  44. negative regulation of anoikis Source: UniProtKB
  45. negative regulation of apoptotic process Source: UniProtKB
  46. negative regulation of apoptotic signaling pathway Source: UniProtKB
  47. negative regulation of autophagy Source: UniProtKB
  48. negative regulation of calcium ion transport into cytosol Source: Ensembl
  49. negative regulation of cell growth Source: Ensembl
  50. negative regulation of cell migration Source: Ensembl
  51. negative regulation of cellular pH reduction Source: UniProtKB
  52. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  53. negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
  54. negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  55. negative regulation of mitochondrial depolarization Source: UniProtKB
  56. negative regulation of mitotic cell cycle Source: Ensembl
  57. negative regulation of myeloid cell apoptotic process Source: Ensembl
  58. negative regulation of neuron apoptotic process Source: MGI
  59. negative regulation of ossification Source: Ensembl
  60. negative regulation of osteoblast proliferation Source: Ensembl
  61. negative regulation of retinal cell programmed cell death Source: Ensembl
  62. neuron apoptotic process Source: HGNC
  63. nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Source: Reactome
  64. oocyte development Source: Ensembl
  65. organ growth Source: Ensembl
  66. ossification Source: Ensembl
  67. ovarian follicle development Source: Ensembl
  68. peptidyl-serine phosphorylation Source: Ensembl
  69. peptidyl-threonine phosphorylation Source: Ensembl
  70. pigment granule organization Source: Ensembl
  71. positive regulation of B cell proliferation Source: UniProtKB
  72. positive regulation of catalytic activity Source: Ensembl
  73. positive regulation of cell growth Source: MGI
  74. positive regulation of intrinsic apoptotic signaling pathway Source: Reactome
  75. positive regulation of melanocyte differentiation Source: Ensembl
  76. positive regulation of multicellular organism growth Source: Ensembl
  77. positive regulation of neuron maturation Source: Ensembl
  78. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
  79. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  80. positive regulation of skeletal muscle fiber development Source: Ensembl
  81. positive regulation of smooth muscle cell migration Source: Ensembl
  82. post-embryonic development Source: Ensembl
  83. protein dephosphorylation Source: Ensembl
  84. protein polyubiquitination Source: MGI
  85. reactive oxygen species metabolic process Source: Ensembl
  86. regulation of calcium ion transport Source: MGI
  87. regulation of cell-matrix adhesion Source: Ensembl
  88. regulation of glycoprotein biosynthetic process Source: Ensembl
  89. regulation of mitochondrial membrane permeability Source: HGNC
  90. regulation of mitochondrial membrane potential Source: HGNC
  91. regulation of nitrogen utilization Source: Ensembl
  92. regulation of protein heterodimerization activity Source: UniProtKB
  93. regulation of protein homodimerization activity Source: UniProtKB
  94. regulation of protein stability Source: Ensembl
  95. regulation of transmembrane transporter activity Source: BHF-UCL
  96. regulation of viral genome replication Source: Ensembl
  97. release of cytochrome c from mitochondria Source: UniProtKB
  98. renal system process Source: Ensembl
  99. response to acid chemical Source: Ensembl
  100. response to cytokine Source: MGI
  101. response to drug Source: UniProtKB
  102. response to gamma radiation Source: Ensembl
  103. response to glucocorticoid Source: Ensembl
  104. response to hydrogen peroxide Source: Ensembl
  105. response to iron ion Source: UniProtKB
  106. response to ischemia Source: Ensembl
  107. response to nicotine Source: UniProtKB
  108. response to radiation Source: UniProtKB
  109. response to toxic substance Source: HGNC
  110. response to UV-B Source: Ensembl
  111. single organismal cell-cell adhesion Source: Ensembl
  112. spleen development Source: Ensembl
  113. T cell differentiation in thymus Source: Ensembl
  114. T cell homeostasis Source: Ensembl
  115. thymus development Source: Ensembl
  116. transmembrane transport Source: GOC
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
REACT_75927. The NLRP1 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulator Bcl-2
Gene namesi
Name:BCL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:990. BCL2.

Subcellular locationi

Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication. Nucleus membrane 1 Publication; Single-pass membrane protein 1 Publication. Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Ensembl
  3. endoplasmic reticulum Source: UniProtKB
  4. endoplasmic reticulum membrane Source: Ensembl
  5. membrane Source: MGI
  6. mitochondrial outer membrane Source: UniProtKB
  7. mitochondrion Source: UniProtKB
  8. myelin sheath Source: Ensembl
  9. nuclear membrane Source: UniProtKB
  10. nucleus Source: MGI
  11. pore complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi34 – 341D → A: Abolishes cleavage by caspase-3.
Mutagenesisi64 – 641D → A: No effect on cleavage by caspase-3.
Mutagenesisi145 – 1451G → A: No heterodimerization with BAX and loss of anti-apoptotic activity.
Mutagenesisi188 – 1881W → A: No heterodimerization with BAX and loss of anti-apoptotic activity.

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

MIMi151430. gene+phenotype.
Orphaneti545. Follicular lymphoma.
98839. Intravascular large B-cell lymphoma.
PharmGKBiPA25302.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 239239Apoptosis regulator Bcl-2PRO_0000143048Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei69 – 691Phosphothreonine; by MAPK81 Publication
Modified residuei70 – 701Phosphoserine; by MAPK8 and PKC1 Publication
Modified residuei87 – 871Phosphoserine; by MAPK81 Publication

Post-translational modificationi

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.By similarity
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.1 Publication
Monoubiquitinated by PARK2, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP10415.
PaxDbiP10415.
PRIDEiP10415.

PTM databases

PhosphoSiteiP10415.

Miscellaneous databases

PMAP-CutDBP10415.

Expressioni

Tissue specificityi

Expressed in a variety of tissues.

Gene expression databases

BgeeiP10415.
CleanExiHS_BCL2.
ExpressionAtlasiP10415. baseline and differential.
GenevestigatoriP10415.

Organism-specific databases

HPAiCAB000003.

Interactioni

Subunit structurei

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.By similarity13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-77694,EBI-77694
AMBRA1Q9C0C710EBI-77694,EBI-2512975
BADQ929345EBI-77694,EBI-700771
BadQ613376EBI-77694,EBI-400328From a different organism.
BAXQ078129EBI-77694,EBI-516580
BBC3Q9BXH15EBI-77694,EBI-519884
BCAP31P515722EBI-77694,EBI-77683
BCL2L11O435217EBI-77694,EBI-526406
BCL2L11O43521-13EBI-77694,EBI-526416
BCL2L11O43521-24EBI-77694,EBI-526420
BCLAF1Q9NYF82EBI-77694,EBI-437804
BECN1Q1445716EBI-77694,EBI-949378
BIDP559578EBI-77694,EBI-519672
BIKQ133233EBI-77694,EBI-700794
BmfQ91ZE92EBI-77694,EBI-708032From a different organism.
BNIP3LO602382EBI-77694,EBI-849893
BRCA1P383986EBI-77694,EBI-349905
MDM4O151514EBI-77694,EBI-398437
NAF1Q96HR82EBI-77694,EBI-2515597
NLRP1Q9C00012EBI-77694,EBI-1220518
NR4A1P227367EBI-77694,EBI-721550
PMAIP1Q137943EBI-77694,EBI-707392
SIVA1O153042EBI-77694,EBI-520756
TP53P046375EBI-77694,EBI-366083
TP53BP2Q1362513EBI-77694,EBI-77642

Protein-protein interaction databases

BioGridi107068. 92 interactions.
DIPiDIP-1043N.
IntActiP10415. 45 interactions.
MINTiMINT-87089.
STRINGi9606.ENSP00000329623.

Structurei

Secondary structure

1
239
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi11 – 2515
Turni32 – 343
Helixi93 – 10715
Helixi109 – 11810
Turni123 – 1253
Helixi126 – 13712
Turni138 – 1403
Helixi144 – 16320
Helixi169 – 18416
Helixi186 – 1916
Helixi194 – 2029
Helixi203 – 2053

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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/F1-207[»]
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[»]
DisProtiDP00297.
ProteinModelPortaliP10415.
SMRiP10415. Positions 3-207.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10415.

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei212 – 23322HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi10 – 3021BH4Add
BLAST
Motifi93 – 10715BH3Add
BLAST
Motifi136 – 15520BH1Add
BLAST
Motifi187 – 20216BH2Add
BLAST

Domaini

The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG275924.
GeneTreeiENSGT00530000062935.
HOGENOMiHOG000056452.
HOVERGENiHBG004472.
InParanoidiP10415.
KOiK02161.
OMAiIVLKYIH.
OrthoDBiEOG70GMGD.
PhylomeDBiP10415.
TreeFamiTF315834.

Family and domain databases

InterProiIPR013278. 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]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSiPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTiSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00865. bcl-2. 1 hit.
PROSITEiPS50062. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform Alpha (identifier: P10415-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS
60 70 80 90 100
SQPGHTPHPA ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA
110 120 130 140 150
GDDFSRRYRR DFAEMSSQLH LTPFTARGRF ATVVEELFRD GVNWGRIVAF
160 170 180 190 200
FEFGGVMCVE SVNREMSPLV DNIALWMTEY LNRHLHTWIQ DNGGWDAFVE
210 220 230
LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK
Length:239
Mass (Da):26,266
Last modified:April 1, 1993 - v2
Checksum:i3C49F2B714DC9CCB
GO
Isoform Beta (identifier: P10415-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:205
Mass (Da):22,337
Checksum:iE3B15A271F900A84
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti48 – 481I → F in CAA29778. (PubMed:2834197)Curated
Sequence conflicti59 – 591P → T in AAA35591. (PubMed:2875799)Curated
Sequence conflicti96 – 961T → A in AAD14111. (PubMed:1339299)Curated
Sequence conflicti110 – 1101R → G in AAD14111. (PubMed:1339299)Curated
Sequence conflicti117 – 1171S → R in AAA35591. (PubMed:2875799)Curated
Sequence conflicti129 – 1291R → C in CAA29778. (PubMed:2834197)Curated
Isoform Beta (identifier: P10415-2)
Sequence conflicti199 – 1991L → S in AAA51814. (PubMed:3523487)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71T → S.2 Publications
VAR_000827
Natural varianti43 – 431A → T.1 Publication
Corresponds to variant rs1800477 [ dbSNP | Ensembl ].
VAR_014716
Natural varianti59 – 591P → S in non-Hodgkin lymphoma; somatic mutation. 1 Publication
VAR_000828
Natural varianti93 – 931V → I in non-Hodgkin lymphoma; somatic mutation. 1 Publication
VAR_000829

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei196 – 23944DAFVE…YLGHK → VGALGDVSLG in isoform Beta. 1 PublicationVSP_000512Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS11981.1. [P10415-1]
CCDS45882.1. [P10415-2]
PIRiB29409. TVHUB1.
C37332. TVHUA1.
RefSeqiNP_000624.2. NM_000633.2. [P10415-1]
NP_000648.2. NM_000657.2. [P10415-2]
UniGeneiHs.150749.

Genome annotation databases

EnsembliENST00000333681; ENSP00000329623; ENSG00000171791. [P10415-1]
ENST00000398117; ENSP00000381185; ENSG00000171791. [P10415-1]
ENST00000589955; ENSP00000466417; ENSG00000171791. [P10415-2]
GeneIDi596.
KEGGihsa:596.
UCSCiuc002lit.1. human. [P10415-1]
uc002liv.1. human.

Polymorphism databases

DMDMi231632.

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Wikipedia

Bcl-2 entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS11981.1. [P10415-1 ]
CCDS45882.1. [P10415-2 ]
PIRi B29409. TVHUB1.
C37332. TVHUA1.
RefSeqi NP_000624.2. NM_000633.2. [P10415-1 ]
NP_000648.2. NM_000657.2. [P10415-2 ]
UniGenei Hs.150749.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1G5M NMR - A 1-34 [» ]
A 92-207 [» ]
1GJH NMR - A 1-34 [» ]
A 92-207 [» ]
1YSW NMR - A 3-33 [» ]
A 92-206 [» ]
2O21 NMR - A 3-34 [» ]
A 92-207 [» ]
2O22 NMR - A 3-34 [» ]
A 92-207 [» ]
2O2F NMR - A 8-31 [» ]
A 92-204 [» ]
2W3L X-ray 2.10 A/B 92-206 [» ]
2XA0 X-ray 2.70 A/B 1-207 [» ]
4AQ3 X-ray 2.40 A/B/C/D/E/F 1-207 [» ]
4IEH X-ray 2.10 A 1-34 [» ]
A 92-207 [» ]
4LVT X-ray 2.05 A/B 1-34 [» ]
A/B 92-207 [» ]
4LXD X-ray 1.90 A 1-34 [» ]
A 92-207 [» ]
4MAN X-ray 2.07 A/B 1-34 [» ]
A/B 92-207 [» ]
DisProti DP00297.
ProteinModelPortali P10415.
SMRi P10415. Positions 3-207.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107068. 92 interactions.
DIPi DIP-1043N.
IntActi P10415. 45 interactions.
MINTi MINT-87089.
STRINGi 9606.ENSP00000329623.

Chemistry

BindingDBi P10415.
ChEMBLi CHEMBL4860.
DrugBanki DB01248. Docetaxel.
DB01050. Ibuprofen.
DB01229. Paclitaxel.
DB01367. Rasagiline.

PTM databases

PhosphoSitei P10415.

Polymorphism databases

DMDMi 231632.

Proteomic databases

MaxQBi P10415.
PaxDbi P10415.
PRIDEi P10415.

Protocols and materials databases

DNASUi 596.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000333681 ; ENSP00000329623 ; ENSG00000171791 . [P10415-1 ]
ENST00000398117 ; ENSP00000381185 ; ENSG00000171791 . [P10415-1 ]
ENST00000589955 ; ENSP00000466417 ; ENSG00000171791 . [P10415-2 ]
GeneIDi 596.
KEGGi hsa:596.
UCSCi uc002lit.1. human. [P10415-1 ]
uc002liv.1. human.

Organism-specific databases

CTDi 596.
GeneCardsi GC18M060763.
HGNCi HGNC:990. BCL2.
HPAi CAB000003.
MIMi 151430. gene+phenotype.
neXtProti NX_P10415.
Orphaneti 545. Follicular lymphoma.
98839. Intravascular large B-cell lymphoma.
PharmGKBi PA25302.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG275924.
GeneTreei ENSGT00530000062935.
HOGENOMi HOG000056452.
HOVERGENi HBG004472.
InParanoidi P10415.
KOi K02161.
OMAi IVLKYIH.
OrthoDBi EOG70GMGD.
PhylomeDBi P10415.
TreeFami TF315834.

Enzyme and pathway databases

Reactomei REACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
REACT_75927. The NLRP1 inflammasome.

Miscellaneous databases

EvolutionaryTracei P10415.
GeneWikii Bcl-2.
GenomeRNAii 596.
NextBioi 2423.
PMAP-CutDB P10415.
PROi P10415.
SOURCEi Search...

Gene expression databases

Bgeei P10415.
CleanExi HS_BCL2.
ExpressionAtlasi P10415. baseline and differential.
Genevestigatori P10415.

Family and domain databases

InterProi 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 ]
PANTHERi PTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
Pfami PF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view ]
PRINTSi PR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTi SM00265. BH4. 1 hit.
[Graphical view ]
TIGRFAMsi TIGR00865. bcl-2. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. 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. 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. 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. Cited for: INTERACTION WITH FBXO10, UBIQUITINATION, IDENTIFICATION IN THE SCF(FBXO10) COMPLEX.
  31. Cited for: STRUCTURE BY NMR OF 1-207.
  32. Cited for: STRUCTURE BY NMR OF 45-207.
  33. Cited for: STRUCTURE BY NMR OF 44-207.

Entry informationi

Entry nameiBCL2_HUMAN
AccessioniPrimary (citable) accession number: P10415
Secondary accession number(s): C9JHD5
, P10416, Q13842, Q16197
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: April 1, 1993
Last modified: October 29, 2014
This is version 193 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

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