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P41182

- BCL6_HUMAN

UniProt

P41182 - BCL6_HUMAN

Protein

B-cell lymphoma 6 protein

Gene

BCL6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4+ T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation.14 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri518 – 54124C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri546 – 56823C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri574 – 59623C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri602 – 62423C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri630 – 65223C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri658 – 68124C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. chromatin DNA binding Source: Ensembl
    3. metal ion binding Source: UniProtKB-KW
    4. protein binding Source: UniProtKB
    5. sequence-specific DNA binding Source: UniProtKB
    6. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. actin cytoskeleton organization Source: Ensembl
    2. B cell differentiation Source: Ensembl
    3. cell morphogenesis Source: Ensembl
    4. cellular response to DNA damage stimulus Source: UniProtKB
    5. erythrocyte development Source: Ensembl
    6. germinal center formation Source: Ensembl
    7. inflammatory response Source: UniProtKB-KW
    8. negative regulation of B cell apoptotic process Source: UniProtKB
    9. negative regulation of cell growth Source: UniProtKB
    10. negative regulation of cell-matrix adhesion Source: Ensembl
    11. negative regulation of cell proliferation Source: Ensembl
    12. negative regulation of isotype switching to IgE isotypes Source: Ensembl
    13. negative regulation of mast cell cytokine production Source: Ensembl
    14. negative regulation of Rho protein signal transduction Source: Ensembl
    15. negative regulation of T-helper 2 cell differentiation Source: Ensembl
    16. negative regulation of transcription, DNA-templated Source: UniProtKB
    17. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    18. negative regulation of type 2 immune response Source: Ensembl
    19. positive regulation of apoptotic process Source: UniProtKB
    20. positive regulation of B cell proliferation Source: Ensembl
    21. positive regulation of cellular component movement Source: Ensembl
    22. protein import into nucleus, translocation Source: UniProtKB
    23. regulation of germinal center formation Source: UniProtKB
    24. regulation of immune response Source: UniProtKB
    25. regulation of inflammatory response Source: Ensembl
    26. regulation of memory T cell differentiation Source: Ensembl
    27. regulation of Rho GTPase activity Source: Ensembl
    28. Rho protein signal transduction Source: Ensembl
    29. spermatogenesis Source: Ensembl
    30. transcription, DNA-templated Source: UniProtKB-KW
    31. type 2 immune response Source: Ensembl

    Keywords - Molecular functioni

    Activator, Repressor

    Keywords - Biological processi

    Immunity, Inflammatory response, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    B-cell lymphoma 6 protein
    Short name:
    BCL-6
    Alternative name(s):
    B-cell lymphoma 5 protein
    Short name:
    BCL-5
    Protein LAZ-3
    Zinc finger and BTB domain-containing protein 27
    Zinc finger protein 51
    Gene namesi
    Name:BCL6
    Synonyms:BCL5, LAZ3, ZBTB27, ZNF51
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:1001. BCL6.

    Subcellular locationi

    Nucleus 4 Publications

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain. Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region. Translocation t(3;6)(q27;p21) with Histone H4. Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1.
    A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.
    A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi21 – 211N → K: Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with A-116 and 376-Q--Q-379. 2 Publications
    Mutagenesisi116 – 1161H → A: Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with K-21 and 376-Q--Q-379. 2 Publications
    Mutagenesisi190 – 1901T → A: No effect on interaction with PIN1. 2 Publications
    Mutagenesisi250 – 2501S → A: No effect on interaction with PIN1. 2 Publications
    Mutagenesisi260 – 2601S → A: Strongly reduces interaction with PIN1. 2 Publications
    Mutagenesisi333 – 3331S → A: Decrease in phosphorylation by MAPK1. 2 Publications
    Mutagenesisi343 – 3431S → A: Decrease in phosphorylation by MAPK1. 2 Publications
    Mutagenesisi376 – 3794KKYK → QQYQ: Abolishes interaction with HDAC2 and MTA3 as well as transcriptional repressor and transforming activities. Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with K-21 and A-116. 2 Publications
    Mutagenesisi376 – 3761K → R: No effect on acetylation. 2 Publications
    Mutagenesisi377 – 3771K → R: No effect on acetylation. 2 Publications
    Mutagenesisi379 – 3791K → R: Abolishes acetylation. No effect on interaction with MTA3, NCOR1 and NCOR2. 3 Publications
    Mutagenesisi520 – 5234CNEC → GNEG: No effect on DNA-binding, nuclear localization, transcriptional repression activity and interaction with HDAC5. 1 Publication
    Mutagenesisi548 – 5514CDRC → GDRG: No effect on DNA-binding, nuclear localization, transcriptional repression activity and interaction with HDAC5. 1 Publication
    Mutagenesisi576 – 5794CNIC → GNIG: Abolishes DNA-binding and transcriptional repression activity, no effect on nuclear localization and interaction with HDAC5. 1 Publication
    Mutagenesisi604 – 6074CETC → GETG: Abolishes DNA-binding and transcriptional repression activity, perturbs nuclear localization. No effect on interaction with HDAC5. 1 Publication
    Mutagenesisi632 – 6354CEIC → GEIG: Abolishes DNA-binding and transcriptional repression activity, no effect on nuclear localization and interaction with HDAC5. 1 Publication
    Mutagenesisi660 – 6634CEKC → GEKG: Abolishes DNA-binding and transcriptional repression activity, perturbs nuclear localization. No effect on interaction with HDAC5. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    Orphaneti545. Follicular lymphoma.
    98839. Intravascular large B-cell lymphoma.
    98838. Primary mediastinal large B-cell lymphoma.
    PharmGKBiPA25312.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 706706B-cell lymphoma 6 proteinPRO_0000047098Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei333 – 3331Phosphoserine; by MAPK11 Publication
    Modified residuei343 – 3431Phosphoserine; by MAPK11 Publication
    Modified residuei379 – 3791N6-acetyllysine2 Publications

    Post-translational modificationi

    Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-333 and Ser-343. Phosphorylated by ATM in response to genotoxic stress. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.3 Publications
    Polyubiquitinated. Polyubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome.
    Acetylated at Lys-379 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function. Deacetylated by HDAC- and SIR2-dependent pathways.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP41182.
    PaxDbiP41182.
    PRIDEiP41182.

    PTM databases

    PhosphoSiteiP41182.

    Expressioni

    Tissue specificityi

    Expressed in germinal center T- and B-cells and in primary immature dendritic cells.8 Publications

    Inductioni

    Down-regulated during maturation of dendritic cells by selective stimuli such as bacterial lipopolysaccharides (LPS), CD40LG and zymosan. Protein levels decreases upon genotoxic stress in a dose- and time-dependent way.2 Publications

    Gene expression databases

    ArrayExpressiP41182.
    BgeeiP41182.
    CleanExiHS_BCL6.
    GenevestigatoriP41182.

    Organism-specific databases

    HPAiCAB000307.
    HPA004899.

    Interactioni

    Subunit structurei

    Homodimer. Interacts (via BTB domain) with the corepressors BCOR, NCOR1 and SMRT/NCOR2; the interactions are direct. Forms preferably ternary complexes with BCOR and SMRT/NCOR2 on target gene promoters but, on enhancer elements, interacts with SMRT/NCOR2 and HDAC3 to repress proximal gene expression. Interacts with histone deacetylases HDAC2, HDAC5 and HDAC9 (via the catalytic domain). Interacts with ZBTB7 and BCL6B. Interacts with SCF(FBXO11) complex; the interaction is independent of phosphorylation and promotes ubiquitination. Interacts (when phosphorylated) with PIN1; the interaction is required for BCL6 degradation upon genotoxic stress. Interacts with ZBTB17; inhibits ZBTB17 transcriptional activity. Interacts with CTBP1, autoinhibits its transcriptional expression. Interacts with NOTCH1 NCID and SIRT1; leads to a epigenetic repression of selective NOTCH1-target genes. Interacts (nor via BTB domain neither acetylated) with the NuRD complex components CHD4, HDAC1, MBD3 and MTA3; the interaction with MTA3 inhibits BCL6 acetylation and is required for BCL6 transpriptional repression.12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HDAC4P565243EBI-765407,EBI-308629
    HDAC9Q9UKV02EBI-765407,EBI-765444
    ZMYND8Q9ULU43EBI-765407,EBI-765834

    Protein-protein interaction databases

    BioGridi107076. 101 interactions.
    DIPiDIP-2651N.
    IntActiP41182. 66 interactions.
    MINTiMINT-158757.
    STRINGi9606.ENSP00000232014.

    Structurei

    Secondary structure

    1
    706
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi8 – 103
    Helixi14 – 2714
    Turni29 – 313
    Beta strandi34 – 385
    Beta strandi41 – 455
    Helixi47 – 537
    Helixi55 – 617
    Turni64 – 685
    Beta strandi70 – 734
    Helixi80 – 9213
    Beta strandi93 – 953
    Turni99 – 1013
    Helixi102 – 11110
    Helixi115 – 12612
    Beta strandi521 – 5233
    Beta strandi527 – 5293
    Helixi530 – 54011
    Helixi558 – 56811
    Beta strandi573 – 5753
    Turni577 – 5793
    Beta strandi582 – 5843
    Helixi586 – 59611
    Beta strandi601 – 6033
    Turni605 – 6073
    Beta strandi610 – 6134
    Helixi614 – 6207
    Helixi622 – 6254
    Beta strandi633 – 6353
    Beta strandi639 – 6413
    Helixi642 – 6487
    Turni649 – 6524

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1R28X-ray2.20A/B5-129[»]
    1R29X-ray1.30A5-129[»]
    1R2BX-ray2.20A/B5-129[»]
    2EN2NMR-A598-626[»]
    2EOSNMR-A626-654[»]
    2LCENMR-A540-602[»]
    2YRMNMR-A515-544[»]
    3BIMX-ray2.60A/B/C/D/E/F/G/H5-129[»]
    3E4UX-ray2.10A/B/C/D/E/F5-129[»]
    3LBZX-ray2.30A/B5-129[»]
    4CP3X-ray2.30A/B9-128[»]
    ProteinModelPortaliP41182.
    SMRiP41182. Positions 5-129, 472-678.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP41182.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini32 – 9968BTBPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni376 – 3794Required for interaction with NuRD complex and for transcriptional repressor activity

    Domaini

    The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2 (PubMed:18212045). Interaction with corepressors through the BTB domain is needed to facilitate the rapid proliferation and survival of GC B-cells but is not involved in the T(FH) formation and BCL6-mediated suppression of T(H)2 and T(H)17 differentiationrequired for GC formation By similarity.By similarity1 Publication

    Sequence similaritiesi

    Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
    Contains 6 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri518 – 54124C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri546 – 56823C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri574 – 59623C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri602 – 62423C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri630 – 65223C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri658 – 68124C2H2-type 6PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5048.
    HOGENOMiHOG000001556.
    HOVERGENiHBG004831.
    InParanoidiP41182.
    KOiK15618.
    OMAiNECDCRF.
    OrthoDBiEOG7KQ22S.
    PhylomeDBiP41182.
    TreeFamiTF330912.

    Family and domain databases

    Gene3Di3.30.160.60. 5 hits.
    3.30.710.10. 1 hit.
    InterProiIPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR013069. BTB_POZ.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF00651. BTB. 1 hit.
    [Graphical view]
    SMARTiSM00225. BTB. 1 hit.
    SM00355. ZnF_C2H2. 6 hits.
    [Graphical view]
    SUPFAMiSSF54695. SSF54695. 1 hit.
    PROSITEiPS50097. BTB. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 6 hits.
    PS50157. ZINC_FINGER_C2H2_2. 6 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P41182-1) [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

    MASPADSCIQ FTRHASDVLL NLNRLRSRDI LTDVVIVVSR EQFRAHKTVL    50
    MACSGLFYSI FTDQLKCNLS VINLDPEINP EGFCILLDFM YTSRLNLREG 100
    NIMAVMATAM YLQMEHVVDT CRKFIKASEA EMVSAIKPPR EEFLNSRMLM 150
    PQDIMAYRGR EVVENNLPLR SAPGCESRAF APSLYSGLST PPASYSMYSH 200
    LPVSSLLFSD EEFRDVRMPV ANPFPKERAL PCDSARPVPG EYSRPTLEVS 250
    PNVCHSNIYS PKETIPEEAR SDMHYSVAEG LKPAAPSARN APYFPCDKAS 300
    KEEERPSSED EIALHFEPPN APLNRKGLVS PQSPQKSDCQ PNSPTESCSS 350
    KNACILQASG SPPAKSPTDP KACNWKKYKF IVLNSLNQNA KPEGPEQAEL 400
    GRLSPRAYTA PPACQPPMEP ENLDLQSPTK LSASGEDSTI PQASRLNNIV 450
    NRSMTGSPRS SSESHSPLYM HPPKCTSCGS QSPQHAEMCL HTAGPTFPEE 500
    MGETQSEYSD SSCENGAFFC NECDCRFSEE ASLKRHTLQT HSDKPYKCDR 550
    CQASFRYKGN LASHKTVHTG EKPYRCNICG AQFNRPANLK THTRIHSGEK 600
    PYKCETCGAR FVQVAHLRAH VLIHTGEKPY PCEICGTRFR HLQTLKSHLR 650
    IHTGEKPYHC EKCNLHFRHK SQLRLHLRQK HGAITNTKVQ YRVSATDLPP 700
    ELPKAC 706
    Length:706
    Mass (Da):78,846
    Last modified:February 1, 1995 - v1
    Checksum:iE38D83C213DAE2D0
    GO
    Isoform 2 (identifier: P41182-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         514-569: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:650
    Mass (Da):72,367
    Checksum:iADDA180461FAFCE4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti347 – 3471S → A in AAC50054. (PubMed:8235596)Curated
    Sequence conflicti393 – 3931E → G in AAC50054. (PubMed:8235596)Curated
    Sequence conflicti498 – 4981P → A in AAC50054. (PubMed:8235596)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti252 – 2521N → S.
    Corresponds to variant rs34463990 [ dbSNP | Ensembl ].
    VAR_052709
    Natural varianti493 – 4931A → T.
    Corresponds to variant rs2229362 [ dbSNP | Ensembl ].
    VAR_019970
    Natural varianti676 – 6761H → Y.
    Corresponds to variant rs1056936 [ dbSNP | Ensembl ].
    VAR_014825

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei514 – 56956Missing in isoform 2. 1 PublicationVSP_042709Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z21943 mRNA. Translation: CAA79937.1.
    U00115 mRNA. Translation: AAC50054.1.
    S67779 mRNA. No translation available.
    EU139066 mRNA. Translation: ABX45135.1.
    AC072022 Genomic DNA. No translation available.
    CH471052 Genomic DNA. Translation: EAW78140.1.
    CH471052 Genomic DNA. Translation: EAW78141.1.
    BC150184 mRNA. Translation: AAI50185.1.
    CCDSiCCDS3289.1. [P41182-1]
    CCDS46975.1. [P41182-2]
    PIRiA48752.
    I52586.
    RefSeqiNP_001124317.1. NM_001130845.1. [P41182-1]
    NP_001128210.1. NM_001134738.1. [P41182-2]
    NP_001697.2. NM_001706.4. [P41182-1]
    XP_005247751.1. XM_005247694.1. [P41182-1]
    UniGeneiHs.478588.

    Genome annotation databases

    EnsembliENST00000232014; ENSP00000232014; ENSG00000113916. [P41182-1]
    ENST00000406870; ENSP00000384371; ENSG00000113916. [P41182-1]
    ENST00000450123; ENSP00000413122; ENSG00000113916. [P41182-2]
    GeneIDi604.
    KEGGihsa:604.
    UCSCiuc003frp.3. human. [P41182-1]
    uc011bsf.1. human. [P41182-2]

    Polymorphism databases

    DMDMi728952.

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z21943 mRNA. Translation: CAA79937.1 .
    U00115 mRNA. Translation: AAC50054.1 .
    S67779 mRNA. No translation available.
    EU139066 mRNA. Translation: ABX45135.1 .
    AC072022 Genomic DNA. No translation available.
    CH471052 Genomic DNA. Translation: EAW78140.1 .
    CH471052 Genomic DNA. Translation: EAW78141.1 .
    BC150184 mRNA. Translation: AAI50185.1 .
    CCDSi CCDS3289.1. [P41182-1 ]
    CCDS46975.1. [P41182-2 ]
    PIRi A48752.
    I52586.
    RefSeqi NP_001124317.1. NM_001130845.1. [P41182-1 ]
    NP_001128210.1. NM_001134738.1. [P41182-2 ]
    NP_001697.2. NM_001706.4. [P41182-1 ]
    XP_005247751.1. XM_005247694.1. [P41182-1 ]
    UniGenei Hs.478588.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1R28 X-ray 2.20 A/B 5-129 [» ]
    1R29 X-ray 1.30 A 5-129 [» ]
    1R2B X-ray 2.20 A/B 5-129 [» ]
    2EN2 NMR - A 598-626 [» ]
    2EOS NMR - A 626-654 [» ]
    2LCE NMR - A 540-602 [» ]
    2YRM NMR - A 515-544 [» ]
    3BIM X-ray 2.60 A/B/C/D/E/F/G/H 5-129 [» ]
    3E4U X-ray 2.10 A/B/C/D/E/F 5-129 [» ]
    3LBZ X-ray 2.30 A/B 5-129 [» ]
    4CP3 X-ray 2.30 A/B 9-128 [» ]
    ProteinModelPortali P41182.
    SMRi P41182. Positions 5-129, 472-678.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107076. 101 interactions.
    DIPi DIP-2651N.
    IntActi P41182. 66 interactions.
    MINTi MINT-158757.
    STRINGi 9606.ENSP00000232014.

    PTM databases

    PhosphoSitei P41182.

    Polymorphism databases

    DMDMi 728952.

    Proteomic databases

    MaxQBi P41182.
    PaxDbi P41182.
    PRIDEi P41182.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000232014 ; ENSP00000232014 ; ENSG00000113916 . [P41182-1 ]
    ENST00000406870 ; ENSP00000384371 ; ENSG00000113916 . [P41182-1 ]
    ENST00000450123 ; ENSP00000413122 ; ENSG00000113916 . [P41182-2 ]
    GeneIDi 604.
    KEGGi hsa:604.
    UCSCi uc003frp.3. human. [P41182-1 ]
    uc011bsf.1. human. [P41182-2 ]

    Organism-specific databases

    CTDi 604.
    GeneCardsi GC03M187439.
    HGNCi HGNC:1001. BCL6.
    HPAi CAB000307.
    HPA004899.
    MIMi 109565. gene.
    neXtProti NX_P41182.
    Orphaneti 545. Follicular lymphoma.
    98839. Intravascular large B-cell lymphoma.
    98838. Primary mediastinal large B-cell lymphoma.
    PharmGKBi PA25312.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5048.
    HOGENOMi HOG000001556.
    HOVERGENi HBG004831.
    InParanoidi P41182.
    KOi K15618.
    OMAi NECDCRF.
    OrthoDBi EOG7KQ22S.
    PhylomeDBi P41182.
    TreeFami TF330912.

    Miscellaneous databases

    ChiTaRSi BCL6. human.
    EvolutionaryTracei P41182.
    GeneWikii BCL6.
    GenomeRNAii 604.
    NextBioi 2453.
    PROi P41182.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P41182.
    Bgeei P41182.
    CleanExi HS_BCL6.
    Genevestigatori P41182.

    Family and domain databases

    Gene3Di 3.30.160.60. 5 hits.
    3.30.710.10. 1 hit.
    InterProi IPR000210. BTB/POZ-like.
    IPR011333. BTB/POZ_fold.
    IPR013069. BTB_POZ.
    IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF00651. BTB. 1 hit.
    [Graphical view ]
    SMARTi SM00225. BTB. 1 hit.
    SM00355. ZnF_C2H2. 6 hits.
    [Graphical view ]
    SUPFAMi SSF54695. SSF54695. 1 hit.
    PROSITEi PS50097. BTB. 1 hit.
    PS00028. ZINC_FINGER_C2H2_1. 6 hits.
    PS50157. ZINC_FINGER_C2H2_2. 6 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas."
      Kerckaert J.-P., Deweindt C., Tilly H., Quief S., Lecocq G., Bastard C.
      Nat. Genet. 5:66-70(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Skeletal muscle.
    2. "Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma."
      Ye B.H., Lista F., Lo Coco F., Knowles D.M., Offit K., Chaganti R.S.K., Dalla-Favera R.
      Science 262:747-750(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Kruppel-like zinc-finger protein."
      Miki T., Kawamata N., Hirosawa S., Aoki N.
      Blood 83:26-32(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    4. "Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas."
      Baron B.W., Nucifora G., McCabe N., Espinosa R. III, le Beau M.M., McKeithan T.W.
      Proc. Natl. Acad. Sci. U.S.A. 90:5262-5266(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. "Discovery of a novel BCL6 transcript and its expression in lung cancer."
      Mao Y., Xiao X., He D., Luo C., Liu C., Lv D.
      Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    6. "The DNA sequence, annotation and analysis of human chromosome 3."
      Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
      , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
      Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "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 1).
    9. "Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor."
      Niu H., Ye B.H., Dalla-Favera R.
      Genes Dev. 12:1953-1961(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-333 AND SER-343, MUTAGENESIS OF SER-333 AND SER-343, UBIQUITINATION.
    10. "Nonrandom fusion of L-plastin(LCP1) and LAZ3(BCL6) genes by t(3;13)(q27;q14) chromosome translocation in two cases of B-cell non-Hodgkin lymphoma."
      Galiegue-Zouitina S., Quief S., Hildebrand M.P., Denis C., Detourmignies L., Lai J.L., Kerckaert J.P.
      Genes Chromosomes Cancer 26:97-105(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, CHROMOSOMAL TRANSLOCATION WITH LCP1.
    11. "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma."
      Hosokawa Y., Maeda Y., Ichinohasama R., Miura I., Taniwaki M., Seto M.
      Blood 95:2719-2721(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, CHROMOSOMAL TRANSLOCATION WITH IKZF1.
    12. "BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control."
      Shaffer A.L., Yu X., He Y., Boldrick J., Chan E.P., Staudt L.M.
      Immunity 13:199-212(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, TISSUE SPECIFICITY.
    13. "Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-Hodgkin's lymphoma and construction of the histone H4/BCL6 fusion gene, leading to altered expression of Bcl-6."
      Kurata M., Maesako Y., Ueda C., Nishikori M., Akasaka T., Uchiyama T., Ohno H.
      Cancer Res. 62:6224-6230(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, CHROMOSOMAL TRANSLOCATION WITH HISTONE H4.
    14. "Acetylation inactivates the transcriptional repressor BCL6."
      Bereshchenko O.R., Gu W., Dalla-Favera R.
      Nat. Genet. 32:606-613(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, ACETYLATION AT LYS-379, DEACETYLATION, INTERACTION WITH HDAC2, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-376; LYS-377 AND LYS-379.
    15. "The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma."
      Ueda C., Akasaka T., Kurata M., Maesako Y., Nishikori M., Ichinohasama R., Imada K., Uchiyama T., Ohno H.
      Oncogene 21:368-376(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, CHROMOSOMAL TRANSLOCATION WITH IL21R.
    16. "Point mutations in BCL6 DNA-binding domain reveal distinct roles for the six zinc fingers."
      Mascle X., Albagli O., Lemercier C.
      Biochem. Biophys. Res. Commun. 300:391-396(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, DNA-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH HDAC5, MUTAGENESIS OF 520-CYS--CYS-523; 548-CYS--CYS-551; 576-CYS--CYS-579; 604-CYS--CYS-607; 632-CYS--CYS-635 AND 660-CYS--CYS-663.
    17. "The histone deacetylase 9 gene encodes multiple protein isoforms."
      Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A.
      J. Biol. Chem. 278:16059-16072(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HDAC9.
    18. "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation."
      Fujita N., Jaye D.L., Geigerman C., Akyildiz A., Mooney M.R., Boss J.M., Wade P.A.
      Cell 119:75-86(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN B-CELL DIFFERENTIATION, INTERACTION WITH NCOR1; NCOR2 AND NURD COMPLEX, ACETYLATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-379 AND 376-LYS--LYS-379.
    19. "The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B-cells."
      Phan R.T., Dalla-Favera R.
      Nature 432:635-639(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TP53 TRANSCRIPTIONAL REPRESSOR.
    20. "BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-dependent kinase inhibitor p21 and cell cycle arrest in germinal center B cells."
      Phan R.T., Saito M., Basso K., Niu H., Dalla-Favera R.
      Nat. Immunol. 6:1054-1060(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH ZBTB17, TISSUE SPECIFICITY.
    21. "Plastic downregulation of the transcriptional repressor BCL6 during maturation of human dendritic cells."
      Pantano S., Jarrossay D., Saccani S., Bosisio D., Natoli G.
      Exp. Cell Res. 312:1312-1322(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, TISSUE SPECIFICITY.
    22. "Genotoxic stress regulates expression of the proto-oncogene Bcl6 in germinal center B cells."
      Phan R.T., Saito M., Kitagawa Y., Means A.R., Dalla-Favera R.
      Nat. Immunol. 8:1132-1139(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION BY ATM, INDUCTION BY GENOTOXIC STRESS, INTERACTION WITH PIN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF THR-190; SER-250 AND SER-260.
    23. Cited for: FUNCTION AS AUTOINHIBITOR, INTERACTION WITH CTBP1; HDAC2 AND NCOR2, TISSUE SPECIFICITY, MUTAGENESIS OF ASN-21; HIS-116 AND 376-LYS--LYS-379.
    24. "BCL6 positively regulates AID and germinal center gene expression via repression of miR-155."
      Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C., Dalla-Favera R.
      J. Exp. Med. 209:2455-2465(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MIRNA REGULATION, SUBCELLULAR LOCATION.
    25. "FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas."
      Duan S., Cermak L., Pagan J.K., Rossi M., Martinengo C., di Celle P.F., Chapuy B., Shipp M., Chiarle R., Pagano M.
      Nature 481:90-93(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SCF(FBXO11) COMPLEX, UBIQUITINATION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
    26. Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH BCOR; HDAC3; NCOR1 AND NCOR2, DNA-BINDING.
    27. Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 5-129 IN COMPLEX WITH NCOR2.
    28. "Solution structure of the C2H2 type zinc finger (region 598-654) of human B-cell lymphoma 6 protein."
      RIKEN structural genomics initiative (RSGI)
      Submitted (OCT-2007) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 598-657.
    29. Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 5-129.
    30. "Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer."
      Ghetu A.F., Corcoran C.M., Cerchietti L., Bardwell V.J., Melnick A., Prive G.G.
      Mol. Cell 29:384-391(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 5-129 IN COMPLEX WITH BCOR, FUNCTION, SUBUNIT.
    31. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 5-129 IN COMPLEX WITH INHIBITOR.

    Entry informationi

    Entry nameiBCL6_HUMAN
    AccessioniPrimary (citable) accession number: P41182
    Secondary accession number(s): A7E241, B8PSA7, D3DNV5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 156 of the entry and version 1 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 3
      Human chromosome 3: 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