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P41182 (BCL6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 152. Feed History...

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

Names and origin

Protein namesRecommended name:
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 names
Name:BCL6
Synonyms:BCL5, LAZ3, ZBTB27, ZNF51
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length706 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.30

Subunit structure

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. Ref.14 Ref.16 Ref.17 Ref.18 Ref.20 Ref.22 Ref.23 Ref.25 Ref.26 Ref.30

Subcellular location

Nucleus Ref.16 Ref.22 Ref.24 Ref.25.

Tissue specificity

Expressed in germinal center T- and B-cells and in primary immature dendritic cells. Ref.9 Ref.12 Ref.14 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23

Induction

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. Ref.21 Ref.22

Domain

The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2 (Ref.23). 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.

Post-translational modification

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. Ref.9 Ref.22 Ref.25

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. Ref.14 Ref.18

Involvement in disease

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.

Sequence similarities

Contains 1 BTB (POZ) domain.

Contains 6 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseProto-oncogene
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Repressor
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from electronic annotation. Source: Ensembl

Rho protein signal transduction

Inferred from electronic annotation. Source: Ensembl

actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from direct assay Ref.19. Source: UniProtKB

erythrocyte development

Inferred from electronic annotation. Source: Ensembl

germinal center formation

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of B cell apoptotic process

Non-traceable author statement Ref.19. Source: UniProtKB

negative regulation of Rho protein signal transduction

Inferred from electronic annotation. Source: Ensembl

negative regulation of T-helper 2 cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from direct assay PubMed 10490843. Source: UniProtKB

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell-matrix adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of isotype switching to IgE isotypes

Inferred from electronic annotation. Source: Ensembl

negative regulation of mast cell cytokine production

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.19. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of type 2 immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from direct assay PubMed 10490843. Source: UniProtKB

positive regulation of cellular component movement

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus, translocation

Inferred from genetic interaction Ref.15. Source: UniProtKB

regulation of Rho GTPase activity

Inferred from electronic annotation. Source: Ensembl

regulation of germinal center formation

Non-traceable author statement PubMed 7795255. Source: UniProtKB

regulation of immune response

Non-traceable author statement Ref.21. Source: UniProtKB

regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

regulation of memory T cell differentiation

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

type 2 immune response

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleus

Inferred from direct assay PubMed 10898795. Source: UniProtKB

   Molecular_functionchromatin DNA binding

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from direct assay PubMed 12097386. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding

Inferred from direct assay Ref.19. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype Ref.19. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P41182-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P41182-2)

The sequence of this isoform differs from the canonical sequence as follows:
     514-569: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 706706B-cell lymphoma 6 protein
PRO_0000047098

Regions

Domain32 – 9968BTB
Zinc finger518 – 54124C2H2-type 1
Zinc finger546 – 56823C2H2-type 2
Zinc finger574 – 59623C2H2-type 3
Zinc finger602 – 62423C2H2-type 4
Zinc finger630 – 65223C2H2-type 5
Zinc finger658 – 68124C2H2-type 6
Region376 – 3794Required for interation with NuRD complex and for transcriptional repressor activity

Amino acid modifications

Modified residue3331Phosphoserine; by MAPK1 Ref.9
Modified residue3431Phosphoserine; by MAPK1 Ref.9
Modified residue3791N6-acetyllysine Ref.14

Natural variations

Alternative sequence514 – 56956Missing in isoform 2.
VSP_042709
Natural variant2521N → S.
Corresponds to variant rs34463990 [ dbSNP | Ensembl ].
VAR_052709
Natural variant4931A → T.
Corresponds to variant rs2229362 [ dbSNP | Ensembl ].
VAR_019970
Natural variant6761H → Y.
Corresponds to variant rs1056936 [ dbSNP | Ensembl ].
VAR_014825

Experimental info

Mutagenesis211N → 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. Ref.23
Mutagenesis1161H → 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. Ref.23
Mutagenesis1901T → A: No effect on interaction with PIN1. Ref.22
Mutagenesis2501S → A: No effect on interaction with PIN1. Ref.22
Mutagenesis2601S → A: Strongly reduces interaction with PIN1. Ref.22
Mutagenesis3331S → A: Decrease in phosphorylation by MAPK1. Ref.9
Mutagenesis3431S → A: Decrease in phosphorylation by MAPK1. Ref.9
Mutagenesis376 – 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. Ref.14 Ref.18 Ref.23
Mutagenesis3761K → R: No effect on acetylation. Ref.14
Mutagenesis3771K → R: No effect on acetylation. Ref.14
Mutagenesis3791K → R: Abolishes acetylation. No effect on interaction with MTA3, NCOR1 and NCOR2. Ref.14 Ref.18
Mutagenesis520 – 5234CNEC → GNEG: No effect on DNA-binding, nuclear localization, transcriptional repression activity and interaction with HDAC5.
Mutagenesis548 – 5514CDRC → GDRG: No effect on DNA-binding, nuclear localization, transcriptional repression activity and interaction with HDAC5.
Mutagenesis576 – 5794CNIC → GNIG: Abolishes DNA-binding and transcriptional repression activity, no effect on nuclear localization and interaction with HDAC5.
Mutagenesis604 – 6074CETC → GETG: Abolishes DNA-binding and transcriptional repression activity, perturbs nuclear localization. No effect on interaction with HDAC5.
Mutagenesis632 – 6354CEIC → GEIG: Abolishes DNA-binding and transcriptional repression activity, no effect on nuclear localization and interaction with HDAC5. Ref.16
Mutagenesis660 – 6634CEKC → GEKG: Abolishes DNA-binding and transcriptional repression activity, perturbs nuclear localization. No effect on interaction with HDAC5. Ref.16
Sequence conflict3471S → A in AAC50054. Ref.2
Sequence conflict3931E → G in AAC50054. Ref.2
Sequence conflict4981P → A in AAC50054. Ref.2

Secondary structure

......................................................... 706
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: E38D83C213DAE2D0

FASTA70678,846
        10         20         30         40         50         60 
MASPADSCIQ FTRHASDVLL NLNRLRSRDI LTDVVIVVSR EQFRAHKTVL MACSGLFYSI 

        70         80         90        100        110        120 
FTDQLKCNLS VINLDPEINP EGFCILLDFM YTSRLNLREG NIMAVMATAM YLQMEHVVDT 

       130        140        150        160        170        180 
CRKFIKASEA EMVSAIKPPR EEFLNSRMLM PQDIMAYRGR EVVENNLPLR SAPGCESRAF 

       190        200        210        220        230        240 
APSLYSGLST PPASYSMYSH LPVSSLLFSD EEFRDVRMPV ANPFPKERAL PCDSARPVPG 

       250        260        270        280        290        300 
EYSRPTLEVS PNVCHSNIYS PKETIPEEAR SDMHYSVAEG LKPAAPSARN APYFPCDKAS 

       310        320        330        340        350        360 
KEEERPSSED EIALHFEPPN APLNRKGLVS PQSPQKSDCQ PNSPTESCSS KNACILQASG 

       370        380        390        400        410        420 
SPPAKSPTDP KACNWKKYKF IVLNSLNQNA KPEGPEQAEL GRLSPRAYTA PPACQPPMEP 

       430        440        450        460        470        480 
ENLDLQSPTK LSASGEDSTI PQASRLNNIV NRSMTGSPRS SSESHSPLYM HPPKCTSCGS 

       490        500        510        520        530        540 
QSPQHAEMCL HTAGPTFPEE MGETQSEYSD SSCENGAFFC NECDCRFSEE ASLKRHTLQT 

       550        560        570        580        590        600 
HSDKPYKCDR CQASFRYKGN LASHKTVHTG EKPYRCNICG AQFNRPANLK THTRIHSGEK 

       610        620        630        640        650        660 
PYKCETCGAR FVQVAHLRAH VLIHTGEKPY PCEICGTRFR HLQTLKSHLR IHTGEKPYHC 

       670        680        690        700 
EKCNLHFRHK SQLRLHLRQK HGAITNTKVQ YRVSATDLPP ELPKAC 

« Hide

Isoform 2 [UniParc].

Checksum: ADDA180461FAFCE4
Show »

FASTA65072,367

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"CtBP is an essential corepressor for BCL6 autoregulation."
Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A., Ye B.H.
Mol. Cell. Biol. 28:2175-2186(2008) [PubMed] [Europe PMC] [Abstract]
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]"A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters."
Hatzi K., Jiang Y., Huang C., Garrett-Bakelman F., Gearhart M.D., Giannopoulou E.G., Zumbo P., Kirouac K., Bhaskara S., Polo J.M., Kormaksson M., Mackerell A.D. Jr., Xue F., Mason C.E., Hiebert S.W., Prive G.G., Cerchietti L., Bardwell V.J., Elemento O., Melnick A.
Cell Rep. 4:578-588(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH BCOR; HDAC3; NCOR1 AND NCOR2, DNA-BINDING.
[27]"Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain."
Ahmad K.F., Melnick A., Lax S., Bouchard D., Liu J., Kiang C.L., Mayer S., Takahashi S., Licht J.D., Prive G.G.
Mol. Cell 12:1551-1564(2003) [PubMed] [Europe PMC] [Abstract]
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]"Structure of the wild-type human BCL6 POZ domain."
Stead M.A., Rosbrook G.O., Hadden J.M., Trinh C.H., Carr S.B., Wright S.C.
Acta Crystallogr. F 64:1101-1104(2008) [PubMed] [Europe PMC] [Abstract]
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]"A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo."
Cerchietti L.C., Ghetu A.F., Zhu X., Da Silva G.F., Zhong S., Matthews M., Bunting K.L., Polo J.M., Fares C., Arrowsmith C.H., Yang S.N., Garcia M., Coop A., Mackerell A.D. Jr., Prive G.G., Melnick A.
Cancer Cell 17:400-411(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 5-129 IN COMPLEX WITH INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA48752.
I52586.
RefSeqNP_001124317.1. NM_001130845.1.
NP_001128210.1. NM_001134738.1.
NP_001697.2. NM_001706.4.
XP_005247751.1. XM_005247694.1.
UniGeneHs.478588.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP41182.
SMRP41182. Positions 5-129, 471-681.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107076. 100 interactions.
DIPDIP-2651N.
IntActP41182. 66 interactions.
MINTMINT-158757.
STRING9606.ENSP00000232014.

PTM databases

PhosphoSiteP41182.

Polymorphism databases

DMDM728952.

Proteomic databases

PaxDbP41182.
PRIDEP41182.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000232014; ENSP00000232014; ENSG00000113916. [P41182-1]
ENST00000406870; ENSP00000384371; ENSG00000113916. [P41182-1]
ENST00000450123; ENSP00000413122; ENSG00000113916. [P41182-2]
GeneID604.
KEGGhsa:604.
UCSCuc003frp.3. human. [P41182-1]
uc011bsf.1. human. [P41182-2]

Organism-specific databases

CTD604.
GeneCardsGC03M187439.
HGNCHGNC:1001. BCL6.
HPACAB000307.
HPA004899.
MIM109565. gene.
neXtProtNX_P41182.
Orphanet545. Follicular lymphoma.
98839. Intravascular large B-cell lymphoma.
98838. Primary mediastinal large B-cell lymphoma.
PharmGKBPA25312.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000001556.
HOVERGENHBG004831.
InParanoidP41182.
KOK15618.
OMANECDCRF.
OrthoDBEOG7KQ22S.
PhylomeDBP41182.
TreeFamTF330912.

Gene expression databases

ArrayExpressP41182.
BgeeP41182.
CleanExHS_BCL6.
GenevestigatorP41182.

Family and domain databases

Gene3D3.30.160.60. 5 hits.
3.30.710.10. 1 hit.
InterProIPR000210. 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]
PfamPF00651. BTB. 1 hit.
[Graphical view]
SMARTSM00225. BTB. 1 hit.
SM00355. ZnF_C2H2. 6 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 6 hits.
PS50157. ZINC_FINGER_C2H2_2. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBCL6. human.
EvolutionaryTraceP41182.
GeneWikiBCL6.
GenomeRNAi604.
NextBio2453.
PROP41182.
SOURCESearch...

Entry information

Entry nameBCL6_HUMAN
AccessionPrimary (citable) accession number: P41182
Secondary accession number(s): A7E241, B8PSA7, D3DNV5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM