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P10415

- BCL2_HUMAN

UniProt

P10415 - BCL2_HUMAN

Protein

Apoptosis regulator Bcl-2

Gene

BCL2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 192 (01 Oct 2014)
      Sequence version 2 (01 Apr 1993)
      Previous versions | rss
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    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 binding Source: IntAct
    7. protein heterodimerization activity Source: UniProtKB
    8. protein homodimerization activity Source: UniProtKB
    9. sequence-specific DNA binding Source: MGI
    10. 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

    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: UniProtKB-SubCell
    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

    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 MAPK82 Publications
    Modified residuei70 – 701Phosphoserine; by MAPK8 and PKC2 Publications
    Modified residuei87 – 871Phosphoserine; by MAPK82 Publications

    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

    ArrayExpressiP10415.
    BgeeiP10415.
    CleanExiHS_BCL2.
    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/F1-33[»]
    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[»]
    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.
    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

    MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS    50
    SQPGHTPHPA ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA 100
    GDDFSRRYRR DFAEMSSQLH LTPFTARGRF ATVVEELFRD GVNWGRIVAF 150
    FEFGGVMCVE SVNREMSPLV DNIALWMTEY LNRHLHTWIQ DNGGWDAFVE 200
    LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK 239
    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 1-33 [» ]
    A/B/C/D/E/F 92-207 [» ]
    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.
    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

    ArrayExpressi P10415.
    Bgeei P10415.
    CleanExi HS_BCL2.
    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

    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 1, 2014
    This is version 192 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

    Dasty 3