BCL6_HUMAN
ID BCL6_HUMAN Reviewed; 706 AA.
AC P41182; A7E241; B8PSA7; D3DNV5;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=B-cell lymphoma 6 protein;
DE Short=BCL-6;
DE AltName: Full=B-cell lymphoma 5 protein;
DE Short=BCL-5;
DE AltName: Full=Protein LAZ-3;
DE AltName: Full=Zinc finger and BTB domain-containing protein 27;
DE AltName: Full=Zinc finger protein 51;
GN Name=BCL6; Synonyms=BCL5, LAZ3, ZBTB27, ZNF51;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=8220427; DOI=10.1038/ng0993-66;
RA Kerckaert J.-P., Deweindt C., Tilly H., Quief S., Lecocq G., Bastard C.;
RT "LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring
RT chromosome 3q27 translocations in human lymphomas.";
RL Nat. Genet. 5:66-70(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8235596; DOI=10.1126/science.8235596;
RA Ye B.H., Lista F., Lo Coco F., Knowles D.M., Offit K., Chaganti R.S.K.,
RA Dalla-Favera R.;
RT "Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell
RT lymphoma.";
RL Science 262:747-750(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8274740;
RA Miki T., Kawamata N., Hirosawa S., Aoki N.;
RT "Gene involved in the 3q27 translocation associated with B-cell lymphoma,
RT BCL5, encodes a Kruppel-like zinc-finger protein.";
RL Blood 83:26-32(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8506375; DOI=10.1073/pnas.90.11.5262;
RA Baron B.W., Nucifora G., McCabe N., Espinosa R. III, le Beau M.M.,
RA McKeithan T.W.;
RT "Identification of the gene associated with the recurring chromosomal
RT translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5262-5266(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Mao Y., Xiao X., He D., Luo C., Liu C., Lv D.;
RT "Discovery of a novel BCL6 transcript and its expression in lung cancer.";
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-333 AND SER-343,
RP MUTAGENESIS OF SER-333 AND SER-343, AND UBIQUITINATION.
RX PubMed=9649500; DOI=10.1101/gad.12.13.1953;
RA Niu H., Ye B.H., Dalla-Favera R.;
RT "Antigen receptor signaling induces MAP kinase-mediated phosphorylation and
RT degradation of the BCL-6 transcription factor.";
RL Genes Dev. 12:1953-1961(1998).
RN [10]
RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL TRANSLOCATION
RP WITH LCP1.
RX PubMed=10469447;
RX DOI=10.1002/(sici)1098-2264(199910)26:2<97::aid-gcc1>3.0.co;2-9;
RA Galiegue-Zouitina S., Quief S., Hildebrand M.P., Denis C.,
RA Detourmignies L., Lai J.L., Kerckaert J.P.;
RT "Nonrandom fusion of L-plastin(LCP1) and LAZ3(BCL6) genes by
RT t(3;13)(q27;q14) chromosome translocation in two cases of B-cell non-
RT Hodgkin lymphoma.";
RL Genes Chromosomes Cancer 26:97-105(1999).
RN [11]
RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL TRANSLOCATION
RP WITH IKZF1.
RX PubMed=10753856;
RA Hosokawa Y., Maeda Y., Ichinohasama R., Miura I., Taniwaki M., Seto M.;
RT "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to
RT the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient
RT with diffuse large B-cell lymphoma.";
RL Blood 95:2719-2721(2000).
RN [12]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, AND TISSUE SPECIFICITY.
RX PubMed=10981963; DOI=10.1016/s1074-7613(00)00020-0;
RA Shaffer A.L., Yu X., He Y., Boldrick J., Chan E.P., Staudt L.M.;
RT "BCL-6 represses genes that function in lymphocyte differentiation,
RT inflammation, and cell cycle control.";
RL Immunity 13:199-212(2000).
RN [13]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INVOLVEMENT IN B-CELL NON-HODGKIN
RP LYMPHOMA, AND CHROMOSOMAL TRANSLOCATION WITH HISTONE H4.
RX PubMed=12414651;
RA Kurata M., Maesako Y., Ueda C., Nishikori M., Akasaka T., Uchiyama T.,
RA Ohno H.;
RT "Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-Hodgkin's
RT lymphoma and construction of the histone H4/BCL6 fusion gene, leading to
RT altered expression of Bcl-6.";
RL Cancer Res. 62:6224-6230(2002).
RN [14]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, ACETYLATION AT LYS-379,
RP DEACETYLATION, INTERACTION WITH HDAC2, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF LYS-376; LYS-377 AND LYS-379.
RX PubMed=12402037; DOI=10.1038/ng1018;
RA Bereshchenko O.R., Gu W., Dalla-Favera R.;
RT "Acetylation inactivates the transcriptional repressor BCL6.";
RL Nat. Genet. 32:606-613(2002).
RN [15]
RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL TRANSLOCATION
RP WITH IL21R.
RX PubMed=11821949; DOI=10.1038/sj.onc.1205099;
RA Ueda C., Akasaka T., Kurata M., Maesako Y., Nishikori M., Ichinohasama R.,
RA Imada K., Uchiyama T., Ohno H.;
RT "The gene for interleukin-21 receptor is the partner of BCL6 in
RT t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell
RT lymphoma.";
RL Oncogene 21:368-376(2002).
RN [16]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, DNA-BINDING, SUBCELLULAR LOCATION,
RP INTERACTION WITH HDAC5, AND MUTAGENESIS OF 520-CYS--CYS-523;
RP 548-CYS--CYS-551; 576-CYS--CYS-579; 604-CYS--CYS-607; 632-CYS--CYS-635 AND
RP 660-CYS--CYS-663.
RX PubMed=12504096; DOI=10.1016/s0006-291x(02)02873-5;
RA Mascle X., Albagli O., Lemercier C.;
RT "Point mutations in BCL6 DNA-binding domain reveal distinct roles for the
RT six zinc fingers.";
RL Biochem. Biophys. Res. Commun. 300:391-396(2003).
RN [17]
RP INTERACTION WITH HDAC9.
RX PubMed=12590135; DOI=10.1074/jbc.m212935200;
RA Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M.,
RA Zelent A.;
RT "The histone deacetylase 9 gene encodes multiple protein isoforms.";
RL J. Biol. Chem. 278:16059-16072(2003).
RN [18]
RP FUNCTION IN B-CELL DIFFERENTIATION, INTERACTION WITH NCOR1; NCOR2 AND NURD
RP COMPLEX, ACETYLATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-379 AND
RP 376-LYS--LYS-379.
RX PubMed=15454082; DOI=10.1016/j.cell.2004.09.014;
RA Fujita N., Jaye D.L., Geigerman C., Akyildiz A., Mooney M.R., Boss J.M.,
RA Wade P.A.;
RT "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte
RT differentiation.";
RL Cell 119:75-86(2004).
RN [19]
RP FUNCTION AS TP53 TRANSCRIPTIONAL REPRESSOR.
RX PubMed=15577913; DOI=10.1038/nature03147;
RA Phan R.T., Dalla-Favera R.;
RT "The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B-
RT cells.";
RL Nature 432:635-639(2004).
RN [20]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH ZBTB17, AND TISSUE
RP SPECIFICITY.
RX PubMed=16142238; DOI=10.1038/ni1245;
RA Phan R.T., Saito M., Basso K., Niu H., Dalla-Favera R.;
RT "BCL6 interacts with the transcription factor Miz-1 to suppress the cyclin-
RT dependent kinase inhibitor p21 and cell cycle arrest in germinal center B
RT cells.";
RL Nat. Immunol. 6:1054-1060(2005).
RN [21]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16455075; DOI=10.1016/j.yexcr.2005.12.020;
RA Pantano S., Jarrossay D., Saccani S., Bosisio D., Natoli G.;
RT "Plastic downregulation of the transcriptional repressor BCL6 during
RT maturation of human dendritic cells.";
RL Exp. Cell Res. 312:1312-1322(2006).
RN [22]
RP FUNCTION, PHOSPHORYLATION BY ATM, INDUCTION BY GENOTOXIC STRESS,
RP INTERACTION WITH PIN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF THR-190; SER-250 AND SER-260.
RX PubMed=17828269; DOI=10.1038/ni1508;
RA Phan R.T., Saito M., Kitagawa Y., Means A.R., Dalla-Favera R.;
RT "Genotoxic stress regulates expression of the proto-oncogene Bcl6 in
RT germinal center B cells.";
RL Nat. Immunol. 8:1132-1139(2007).
RN [23]
RP FUNCTION AS AUTOINHIBITOR, INTERACTION WITH CTBP1; HDAC2 AND NCOR2, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF ASN-21; HIS-116 AND 376-LYS--LYS-379.
RX PubMed=18212045; DOI=10.1128/mcb.01400-07;
RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A.,
RA Ye B.H.;
RT "CtBP is an essential corepressor for BCL6 autoregulation.";
RL Mol. Cell. Biol. 28:2175-2186(2008).
RN [24]
RP FUNCTION IN MIRNA REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=23166356; DOI=10.1084/jem.20121387;
RA Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C.,
RA Dalla-Favera R.;
RT "BCL6 positively regulates AID and germinal center gene expression via
RT repression of miR-155.";
RL J. Exp. Med. 209:2455-2465(2012).
RN [25]
RP FUNCTION, INTERACTION WITH SCF(FBXO11) COMPLEX, UBIQUITINATION,
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=22113614; DOI=10.1038/nature10688;
RA Duan S., Cermak L., Pagan J.K., Rossi M., Martinengo C., di Celle P.F.,
RA Chapuy B., Shipp M., Chiarle R., Pagano M.;
RT "FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-
RT cell lymphomas.";
RL Nature 481:90-93(2012).
RN [26]
RP FUNCTION AS TRANSCRIPTIONAL REPRESSOR, INTERACTION WITH BCOR; HDAC3; NCOR1
RP AND NCOR2, AND DNA-BINDING.
RX PubMed=23911289; DOI=10.1016/j.celrep.2013.06.016;
RA Hatzi K., Jiang Y., Huang C., Garrett-Bakelman F., Gearhart M.D.,
RA Giannopoulou E.G., Zumbo P., Kirouac K., Bhaskara S., Polo J.M.,
RA Kormaksson M., Mackerell A.D. Jr., Xue F., Mason C.E., Hiebert S.W.,
RA Prive G.G., Cerchietti L., Bardwell V.J., Elemento O., Melnick A.;
RT "A hybrid mechanism of action for BCL6 in B cells defined by formation of
RT functionally distinct complexes at enhancers and promoters.";
RL Cell Rep. 4:578-588(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP UBIQUITINATION, AND MUTAGENESIS OF SER-59.
RX PubMed=30190310; DOI=10.1126/science.aap8236;
RA Mena E.L., Kjolby R.A.S., Saxton R.A., Werner A., Lew B.G., Boyle J.M.,
RA Harland R., Rape M.;
RT "Dimerization quality control ensures neuronal development and survival.";
RL Science 362:eaap8236-eaap8236(2018).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 5-129 IN COMPLEX WITH NCOR2.
RX PubMed=14690607; DOI=10.1016/s1097-2765(03)00454-4;
RA Ahmad K.F., Melnick A., Lax S., Bouchard D., Liu J., Kiang C.L., Mayer S.,
RA Takahashi S., Licht J.D., Prive G.G.;
RT "Mechanism of SMRT corepressor recruitment by the BCL6 BTB domain.";
RL Mol. Cell 12:1551-1564(2003).
RN [30]
RP STRUCTURE BY NMR OF 598-657.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the C2H2 type zinc finger (region 598-654) of human
RT B-cell lymphoma 6 protein.";
RL Submitted (OCT-2007) to the PDB data bank.
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 5-129.
RX PubMed=19052359; DOI=10.1107/s1744309108036063;
RA Stead M.A., Rosbrook G.O., Hadden J.M., Trinh C.H., Carr S.B., Wright S.C.;
RT "Structure of the wild-type human BCL6 POZ domain.";
RL Acta Crystallogr. F 64:1101-1104(2008).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 5-129 IN COMPLEX WITH BCOR,
RP FUNCTION, AND SUBUNIT.
RX PubMed=18280243; DOI=10.1016/j.molcel.2007.12.026;
RA Ghetu A.F., Corcoran C.M., Cerchietti L., Bardwell V.J., Melnick A.,
RA Prive G.G.;
RT "Structure of a BCOR corepressor peptide in complex with the BCL6 BTB
RT domain dimer.";
RL Mol. Cell 29:384-391(2008).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 5-129 IN COMPLEX WITH INHIBITOR.
RX PubMed=20385364; DOI=10.1016/j.ccr.2009.12.050;
RA Cerchietti L.C., Ghetu A.F., Zhu X., Da Silva G.F., Zhong S., Matthews M.,
RA Bunting K.L., Polo J.M., Fares C., Arrowsmith C.H., Yang S.N., Garcia M.,
RA Coop A., Mackerell A.D. Jr., Prive G.G., Melnick A.;
RT "A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in
RT vivo.";
RL Cancer Cell 17:400-411(2010).
CC -!- FUNCTION: Transcriptional repressor mainly required for germinal center
CC (GC) formation and antibody affinity maturation which has different
CC mechanisms of action specific to the lineage and biological functions.
CC Forms complexes with different corepressors and histone deacetylases to
CC repress the transcriptional expression of different subsets of target
CC genes. Represses its target genes by binding directly to the DNA
CC sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by
CC repressing the transcriptional activity of transcription factors. In GC
CC B-cells, represses genes that function in differentiation,
CC inflammation, apoptosis and cell cycle control, also autoregulates its
CC transcriptional expression and up-regulates, indirectly, the expression
CC of some genes important for GC reactions, such as AICDA, through the
CC repression of microRNAs expression, like miR155. An important function
CC is to allow GC B-cells to proliferate very rapidly in response to T-
CC cell dependent antigens and tolerate the physiological DNA breaks
CC required for immunglobulin class switch recombination and somatic
CC hypermutation without inducing a p53/TP53-dependent apoptotic response.
CC In follicular helper CD4(+) T-cells (T(FH) cells), promotes the
CC expression of T(FH)-related genes but inhibits the differentiation of
CC T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and
CC maintenance of immunological memory for both T- and B-cells. Suppresses
CC macrophage proliferation through competition with STAT5 for STAT-
CC binding motifs binding on certain target genes, such as CCL2 and CCND2.
CC In response to genotoxic stress, controls cell cycle arrest in GC B-
CC cells in both p53/TP53-dependedent and -independent manners. Besides,
CC also controls neurogenesis through the alteration of the composition of
CC NOTCH-dependent transcriptional complexes at selective NOTCH targets,
CC such as HES5, including the recruitment of the deacetylase SIRT1 and
CC resulting in an epigenetic silencing leading to neuronal
CC differentiation. {ECO:0000269|PubMed:10981963,
CC ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:12414651,
CC ECO:0000269|PubMed:12504096, ECO:0000269|PubMed:15454082,
CC ECO:0000269|PubMed:15577913, ECO:0000269|PubMed:16142238,
CC ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18212045,
CC ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:22113614,
CC ECO:0000269|PubMed:23166356, ECO:0000269|PubMed:23911289,
CC ECO:0000269|PubMed:9649500}.
CC -!- SUBUNIT: Homodimer. Interacts (via BTB domain) with the corepressors
CC BCOR, NCOR1 and SMRT/NCOR2; the interactions are direct. Forms
CC preferably ternary complexes with BCOR and SMRT/NCOR2 on target gene
CC promoters but, on enhancer elements, interacts with SMRT/NCOR2 and
CC HDAC3 to repress proximal gene expression. Interacts with histone
CC deacetylases HDAC2, HDAC5 and HDAC9 (via the catalytic domain).
CC Interacts with ZBTB7 and BCL6B. Interacts with SCF(FBXO11) complex; the
CC interaction is independent of phosphorylation and promotes
CC ubiquitination. Interacts (when phosphorylated) with PIN1; the
CC interaction is required for BCL6 degradation upon genotoxic stress.
CC Interacts with ZBTB17; inhibits ZBTB17 transcriptional activity.
CC Interacts with CTBP1, autoinhibits its transcriptional expression.
CC Interacts with NOTCH1 NCID and SIRT1; leads to a epigenetic repression
CC of selective NOTCH1-target genes. Interacts (nor via BTB domain neither
CC acetylated) with the NuRD complex components CHD4, HDAC1, MBD3 and
CC MTA3; the interaction with MTA3 inhibits BCL6 acetylation and is
CC required for BCL6 transpriptional repression.
CC {ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:12504096,
CC ECO:0000269|PubMed:12590135, ECO:0000269|PubMed:14690607,
CC ECO:0000269|PubMed:15454082, ECO:0000269|PubMed:16142238,
CC ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18212045,
CC ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:20385364,
CC ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23911289}.
CC -!- INTERACTION:
CC P41182; Q8N9V6-2: ANKRD53; NbExp=3; IntAct=EBI-765407, EBI-13345447;
CC P41182; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-765407, EBI-2875665;
CC P41182; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-765407, EBI-12811889;
CC P41182; P41182: BCL6; NbExp=4; IntAct=EBI-765407, EBI-765407;
CC P41182; A8KA13: BCL6B; NbExp=3; IntAct=EBI-765407, EBI-10174813;
CC P41182; Q9H2G9: BLZF1; NbExp=4; IntAct=EBI-765407, EBI-2548012;
CC P41182; Q96LM5: C4orf45; NbExp=3; IntAct=EBI-765407, EBI-12020542;
CC P41182; Q8N865: C7orf31; NbExp=3; IntAct=EBI-765407, EBI-10174456;
CC P41182; Q6P656: CFAP161; NbExp=3; IntAct=EBI-765407, EBI-11901329;
CC P41182; B2RV13: CFAP97D1; NbExp=3; IntAct=EBI-765407, EBI-12870048;
CC P41182; Q9NZN8: CNOT2; NbExp=3; IntAct=EBI-765407, EBI-743033;
CC P41182; Q9NTM9: CUTC; NbExp=3; IntAct=EBI-765407, EBI-714918;
CC P41182; Q86XK2: FBXO11; NbExp=9; IntAct=EBI-765407, EBI-1047804;
CC P41182; Q08379: GOLGA2; NbExp=5; IntAct=EBI-765407, EBI-618309;
CC P41182; P56524: HDAC4; NbExp=3; IntAct=EBI-765407, EBI-308629;
CC P41182; Q9UKV0: HDAC9; NbExp=2; IntAct=EBI-765407, EBI-765444;
CC P41182; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-765407, EBI-2125614;
CC P41182; Q53G59: KLHL12; NbExp=3; IntAct=EBI-765407, EBI-740929;
CC P41182; Q9BS75: KLHL20; NbExp=3; IntAct=EBI-765407, EBI-10693436;
CC P41182; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-765407, EBI-11953846;
CC P41182; Q8IUB9: KRTAP19-1; NbExp=3; IntAct=EBI-765407, EBI-12811111;
CC P41182; P0CW20: LIMS4; NbExp=6; IntAct=EBI-765407, EBI-10196832;
CC P41182; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-765407, EBI-10302990;
CC P41182; Q99471: PFDN5; NbExp=3; IntAct=EBI-765407, EBI-357275;
CC P41182; Q8WVV4-1: POF1B; NbExp=3; IntAct=EBI-765407, EBI-11986735;
CC P41182; Q8NI37: PPTC7; NbExp=3; IntAct=EBI-765407, EBI-9089276;
CC P41182; P28070: PSMB4; NbExp=3; IntAct=EBI-765407, EBI-603350;
CC P41182; Q04864-2: REL; NbExp=3; IntAct=EBI-765407, EBI-10829018;
CC P41182; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-765407, EBI-747107;
CC P41182; Q8NCR6: SMRP1; NbExp=3; IntAct=EBI-765407, EBI-10269322;
CC P41182; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-765407, EBI-750487;
CC P41182; Q08117: TLE5; NbExp=3; IntAct=EBI-765407, EBI-717810;
CC P41182; Q12888: TP53BP1; NbExp=3; IntAct=EBI-765407, EBI-396540;
CC P41182; Q13077: TRAF1; NbExp=5; IntAct=EBI-765407, EBI-359224;
CC P41182; Q12933: TRAF2; NbExp=3; IntAct=EBI-765407, EBI-355744;
CC P41182; Q96RU7: TRIB3; NbExp=4; IntAct=EBI-765407, EBI-492476;
CC P41182; Q9BRX9: WDR83; NbExp=3; IntAct=EBI-765407, EBI-7705033;
CC P41182; O15156: ZBTB7B; NbExp=3; IntAct=EBI-765407, EBI-740434;
CC P41182; Q9ULU4: ZMYND8; NbExp=3; IntAct=EBI-765407, EBI-765834;
CC P41182; O43257: ZNHIT1; NbExp=3; IntAct=EBI-765407, EBI-347522;
CC P41182; P45481: Crebbp; Xeno; NbExp=2; IntAct=EBI-765407, EBI-296306;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12504096,
CC ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:22113614,
CC ECO:0000269|PubMed:23166356}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P41182-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P41182-2; Sequence=VSP_042709;
CC -!- TISSUE SPECIFICITY: Expressed in germinal center T- and B-cells and in
CC primary immature dendritic cells. {ECO:0000269|PubMed:10981963,
CC ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:15454082,
CC ECO:0000269|PubMed:16142238, ECO:0000269|PubMed:16455075,
CC ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18212045,
CC ECO:0000269|PubMed:9649500}.
CC -!- INDUCTION: Down-regulated during maturation of dendritic cells by
CC selective stimuli such as bacterial lipopolysaccharides (LPS), CD40LG
CC and zymosan. Protein levels decreases upon genotoxic stress in a
CC dose- and time-dependent way. {ECO:0000269|PubMed:16455075,
CC ECO:0000269|PubMed:17828269}.
CC -!- DOMAIN: The BTB domain mediates homodimerization. Its dimer interface
CC mediates peptide binding such as to corepressors BCOR and NCOR2
CC (PubMed:18212045). Interaction with corepressors through the BTB domain
CC is needed to facilitate the rapid proliferation and survival of GC B-
CC cells but is not involved in the T(FH) formation and BCL6-mediated
CC suppression of T(H)2 and T(H)17 differentiationrequired for GC
CC formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:18212045}.
CC -!- PTM: Phosphorylated by MAPK1 in response to antigen receptor activation
CC at Ser-333 and Ser-343. Phosphorylated by ATM in response to genotoxic
CC stress. Phosphorylation induces its degradation by ubiquitin/proteasome
CC pathway. {ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:22113614,
CC ECO:0000269|PubMed:9649500}.
CC -!- PTM: Polyubiquitinated (PubMed:9649500, PubMed:22113614,
CC PubMed:30190310). Polyubiquitinated by SCF(FBXO11), leading to its
CC degradation by the proteasome (PubMed:22113614). Ubiquitinated by the
CC SCF(FBXL17) complex, leading to its degradation by the proteasome:
CC ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB
CC domain dimers are formed (PubMed:30190310).
CC {ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:30190310,
CC ECO:0000269|PubMed:9649500}.
CC -!- PTM: Acetylated at Lys-379 by EP300 which inhibits the interaction with
CC NuRD complex and the transcriptional repressor function. Deacetylated
CC by HDAC- and SIR2-dependent pathways. {ECO:0000269|PubMed:12402037,
CC ECO:0000269|PubMed:15454082}.
CC -!- DISEASE: Note=Chromosomal aberrations involving BCL6 are a cause of B-
CC cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell
CC lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-
CC cell lymphomas and 5 to 10% of follicular lymphomas are associated with
CC chromosomal translocations that deregulate expression of BCL6 by
CC juxtaposing heterologous promoters to the BCL6 coding domain
CC (PubMed:10469447, PubMed:10753856, PubMed:12414651, PubMed:11821949).
CC Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with
CC immunoglobulin gene regions (PubMed:11821949). Translocation
CC t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region (PubMed:10753856).
CC Translocation t(3;6)(q27;p21) with Histone H4 (PubMed:12414651).
CC Translocation t(3;16)(q27;p11) with IL21R. Translocation
CC t(3;13)(q27;q14) with LCP1 (PubMed:10469447).
CC {ECO:0000269|PubMed:10469447, ECO:0000269|PubMed:10753856,
CC ECO:0000269|PubMed:11821949, ECO:0000269|PubMed:12414651}.
CC -!- DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of
CC a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with
CC POU2AF1/OBF1.
CC -!- DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of
CC lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL6ID20.html";
CC ---------------------------------------------------------------------------
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DR EMBL; Z21943; CAA79937.1; -; mRNA.
DR EMBL; U00115; AAC50054.1; -; mRNA.
DR EMBL; S67779; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; EU139066; ABX45135.1; -; mRNA.
DR EMBL; AC072022; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78140.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78141.1; -; Genomic_DNA.
DR EMBL; BC150184; AAI50185.1; -; mRNA.
DR CCDS; CCDS3289.1; -. [P41182-1]
DR CCDS; CCDS46975.1; -. [P41182-2]
DR PIR; A48752; A48752.
DR PIR; I52586; I52586.
DR RefSeq; NP_001124317.1; NM_001130845.1. [P41182-1]
DR RefSeq; NP_001128210.1; NM_001134738.1. [P41182-2]
DR RefSeq; NP_001697.2; NM_001706.4. [P41182-1]
DR RefSeq; XP_005247751.1; XM_005247694.3. [P41182-1]
DR RefSeq; XP_011511364.1; XM_011513062.2. [P41182-2]
DR PDB; 1R28; X-ray; 2.20 A; A/B=5-129.
DR PDB; 1R29; X-ray; 1.30 A; A=5-129.
DR PDB; 1R2B; X-ray; 2.20 A; A/B=5-129.
DR PDB; 2EN2; NMR; -; A=598-626.
DR PDB; 2EOS; NMR; -; A=626-654.
DR PDB; 2LCE; NMR; -; A=540-602.
DR PDB; 2YRM; NMR; -; A=515-544.
DR PDB; 3BIM; X-ray; 2.60 A; A/B/C/D/E/F/G/H=5-129.
DR PDB; 3E4U; X-ray; 2.10 A; A/B/C/D/E/F=5-129.
DR PDB; 3LBZ; X-ray; 2.30 A; A/B=5-129.
DR PDB; 4CP3; X-ray; 2.30 A; A/B=9-128.
DR PDB; 4U2M; X-ray; 2.23 A; A/B/C/D=5-129.
DR PDB; 5H7G; X-ray; 1.85 A; A/B=5-129.
DR PDB; 5H7H; X-ray; 1.95 A; A=5-129.
DR PDB; 5MW2; X-ray; 2.35 A; A=5-129.
DR PDB; 5MW6; X-ray; 1.65 A; A/B=5-129.
DR PDB; 5MWD; X-ray; 1.85 A; A=5-129.
DR PDB; 5N1X; X-ray; 1.72 A; A=9-128, B/C=7-127, D=9-125.
DR PDB; 5N1Z; X-ray; 1.81 A; A=6-128.
DR PDB; 5N20; X-ray; 1.38 A; A=6-128.
DR PDB; 5N21; X-ray; 1.58 A; A/B=7-128.
DR PDB; 5X4M; X-ray; 1.65 A; A=5-129.
DR PDB; 5X4N; X-ray; 1.94 A; A=5-129.
DR PDB; 5X4O; X-ray; 2.05 A; A=5-129.
DR PDB; 5X4P; X-ray; 2.06 A; A=5-129.
DR PDB; 5X4Q; X-ray; 2.00 A; A=5-129.
DR PDB; 5X9O; X-ray; 1.58 A; A=5-129.
DR PDB; 5X9P; X-ray; 1.86 A; A=5-129.
DR PDB; 6C3L; X-ray; 1.46 A; A/B=5-129.
DR PDB; 6C3N; X-ray; 2.53 A; A/B=1-129.
DR PDB; 6CQ1; X-ray; 1.70 A; A/B=1-129.
DR PDB; 6EW6; X-ray; 1.39 A; A=6-128.
DR PDB; 6EW7; X-ray; 1.60 A; A/B=7-128.
DR PDB; 6EW8; X-ray; 1.84 A; A=6-129.
DR PDB; 6TBT; X-ray; 1.63 A; A/B=6-129.
DR PDB; 6TCJ; X-ray; 2.13 A; A/B=6-129.
DR PDB; 6TOF; X-ray; 1.67 A; A=5-129.
DR PDB; 6TOG; X-ray; 1.69 A; A=5-129.
DR PDB; 6TOH; X-ray; 1.58 A; A=5-129.
DR PDB; 6TOI; X-ray; 1.58 A; A=5-129.
DR PDB; 6TOJ; X-ray; 1.85 A; A=5-129.
DR PDB; 6TOK; X-ray; 1.43 A; A=5-129.
DR PDB; 6TOL; X-ray; 1.64 A; A=5-129.
DR PDB; 6TOM; X-ray; 1.90 A; A=5-129.
DR PDB; 6TON; X-ray; 2.36 A; A=5-129.
DR PDB; 6TOO; X-ray; 1.53 A; A=5-129.
DR PDB; 6XMX; EM; 3.70 A; A/B/C/D/E/F/G/H=5-360.
DR PDB; 6XWF; X-ray; 1.60 A; A=6-129.
DR PDB; 6XXS; X-ray; 3.25 A; A/B/E/F=6-129.
DR PDB; 6XYX; X-ray; 1.44 A; A/B=6-129.
DR PDB; 6XZZ; X-ray; 1.39 A; A=6-129.
DR PDB; 6Y17; X-ray; 1.56 A; A/B=6-129.
DR PDB; 6ZBU; X-ray; 2.46 A; A/B/E/F/I/J=6-129.
DR PDB; 7BDE; X-ray; 2.04 A; A=5-129.
DR PDB; 7LWE; X-ray; 1.17 A; A=1-129.
DR PDB; 7LWF; X-ray; 1.22 A; A=5-129.
DR PDB; 7LWG; X-ray; 1.30 A; A/B=5-129.
DR PDB; 7LZR; X-ray; 1.34 A; A/B/C/D=5-129.
DR PDB; 7LZS; X-ray; 1.49 A; A=5-129.
DR PDB; 7OKD; X-ray; 1.94 A; A=5-129.
DR PDB; 7OKE; X-ray; 1.48 A; A=5-129.
DR PDB; 7OKF; X-ray; 1.60 A; A=5-129.
DR PDB; 7OKG; X-ray; 1.32 A; A=5-129.
DR PDB; 7OKH; X-ray; 1.52 A; A=5-129.
DR PDB; 7OKI; X-ray; 1.61 A; A=5-129.
DR PDB; 7OKJ; X-ray; 1.43 A; A=5-129.
DR PDB; 7OKK; X-ray; 2.05 A; A=5-129.
DR PDB; 7OKL; X-ray; 1.20 A; A=5-129.
DR PDB; 7OKM; X-ray; 1.48 A; A=5-129.
DR PDBsum; 1R28; -.
DR PDBsum; 1R29; -.
DR PDBsum; 1R2B; -.
DR PDBsum; 2EN2; -.
DR PDBsum; 2EOS; -.
DR PDBsum; 2LCE; -.
DR PDBsum; 2YRM; -.
DR PDBsum; 3BIM; -.
DR PDBsum; 3E4U; -.
DR PDBsum; 3LBZ; -.
DR PDBsum; 4CP3; -.
DR PDBsum; 4U2M; -.
DR PDBsum; 5H7G; -.
DR PDBsum; 5H7H; -.
DR PDBsum; 5MW2; -.
DR PDBsum; 5MW6; -.
DR PDBsum; 5MWD; -.
DR PDBsum; 5N1X; -.
DR PDBsum; 5N1Z; -.
DR PDBsum; 5N20; -.
DR PDBsum; 5N21; -.
DR PDBsum; 5X4M; -.
DR PDBsum; 5X4N; -.
DR PDBsum; 5X4O; -.
DR PDBsum; 5X4P; -.
DR PDBsum; 5X4Q; -.
DR PDBsum; 5X9O; -.
DR PDBsum; 5X9P; -.
DR PDBsum; 6C3L; -.
DR PDBsum; 6C3N; -.
DR PDBsum; 6CQ1; -.
DR PDBsum; 6EW6; -.
DR PDBsum; 6EW7; -.
DR PDBsum; 6EW8; -.
DR PDBsum; 6TBT; -.
DR PDBsum; 6TCJ; -.
DR PDBsum; 6TOF; -.
DR PDBsum; 6TOG; -.
DR PDBsum; 6TOH; -.
DR PDBsum; 6TOI; -.
DR PDBsum; 6TOJ; -.
DR PDBsum; 6TOK; -.
DR PDBsum; 6TOL; -.
DR PDBsum; 6TOM; -.
DR PDBsum; 6TON; -.
DR PDBsum; 6TOO; -.
DR PDBsum; 6XMX; -.
DR PDBsum; 6XWF; -.
DR PDBsum; 6XXS; -.
DR PDBsum; 6XYX; -.
DR PDBsum; 6XZZ; -.
DR PDBsum; 6Y17; -.
DR PDBsum; 6ZBU; -.
DR PDBsum; 7BDE; -.
DR PDBsum; 7LWE; -.
DR PDBsum; 7LWF; -.
DR PDBsum; 7LWG; -.
DR PDBsum; 7LZR; -.
DR PDBsum; 7LZS; -.
DR PDBsum; 7OKD; -.
DR PDBsum; 7OKE; -.
DR PDBsum; 7OKF; -.
DR PDBsum; 7OKG; -.
DR PDBsum; 7OKH; -.
DR PDBsum; 7OKI; -.
DR PDBsum; 7OKJ; -.
DR PDBsum; 7OKK; -.
DR PDBsum; 7OKL; -.
DR PDBsum; 7OKM; -.
DR AlphaFoldDB; P41182; -.
DR SMR; P41182; -.
DR BioGRID; 107076; 171.
DR CORUM; P41182; -.
DR DIP; DIP-2651N; -.
DR IntAct; P41182; 125.
DR MINT; P41182; -.
DR STRING; 9606.ENSP00000384371; -.
DR BindingDB; P41182; -.
DR ChEMBL; CHEMBL4105786; -.
DR GuidetoPHARMACOLOGY; 2957; -.
DR iPTMnet; P41182; -.
DR PhosphoSitePlus; P41182; -.
DR BioMuta; BCL6; -.
DR DMDM; 728952; -.
DR EPD; P41182; -.
DR jPOST; P41182; -.
DR MassIVE; P41182; -.
DR MaxQB; P41182; -.
DR PaxDb; P41182; -.
DR PeptideAtlas; P41182; -.
DR PRIDE; P41182; -.
DR ProteomicsDB; 55413; -. [P41182-1]
DR ProteomicsDB; 55414; -. [P41182-2]
DR TopDownProteomics; P41182-2; -. [P41182-2]
DR Antibodypedia; 1434; 1130 antibodies from 50 providers.
DR DNASU; 604; -.
DR Ensembl; ENST00000232014.8; ENSP00000232014.4; ENSG00000113916.18. [P41182-1]
DR Ensembl; ENST00000406870.7; ENSP00000384371.2; ENSG00000113916.18. [P41182-1]
DR Ensembl; ENST00000450123.6; ENSP00000413122.2; ENSG00000113916.18. [P41182-2]
DR Ensembl; ENST00000621333.4; ENSP00000479784.1; ENSG00000113916.18. [P41182-2]
DR GeneID; 604; -.
DR KEGG; hsa:604; -.
DR MANE-Select; ENST00000406870.7; ENSP00000384371.2; NM_001706.5; NP_001697.2.
DR UCSC; uc003frp.4; human. [P41182-1]
DR CTD; 604; -.
DR DisGeNET; 604; -.
DR GeneCards; BCL6; -.
DR HGNC; HGNC:1001; BCL6.
DR HPA; ENSG00000113916; Tissue enhanced (skeletal).
DR MalaCards; BCL6; -.
DR MIM; 109565; gene.
DR neXtProt; NX_P41182; -.
DR OpenTargets; ENSG00000113916; -.
DR Orphanet; 545; Follicular lymphoma.
DR Orphanet; 480541; High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement.
DR Orphanet; 98839; Intravascular large B-cell lymphoma.
DR Orphanet; 98838; Primary mediastinal large B-cell lymphoma.
DR PharmGKB; PA25312; -.
DR VEuPathDB; HostDB:ENSG00000113916; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000156311; -.
DR HOGENOM; CLU_024196_1_0_1; -.
DR InParanoid; P41182; -.
DR OMA; RMPMANP; -.
DR OrthoDB; 80538at2759; -.
DR PhylomeDB; P41182; -.
DR TreeFam; TF330912; -.
DR PathwayCommons; P41182; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-6803205; TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
DR Reactome; R-HSA-9614657; FOXO-mediated transcription of cell death genes.
DR SignaLink; P41182; -.
DR SIGNOR; P41182; -.
DR BioGRID-ORCS; 604; 41 hits in 1141 CRISPR screens.
DR ChiTaRS; BCL6; human.
DR EvolutionaryTrace; P41182; -.
DR GeneWiki; BCL6; -.
DR GenomeRNAi; 604; -.
DR Pharos; P41182; Tchem.
DR PRO; PR:P41182; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P41182; protein.
DR Bgee; ENSG00000113916; Expressed in gastrocnemius and 209 other tissues.
DR ExpressionAtlas; P41182; baseline and differential.
DR Genevisible; P41182; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042382; C:paraspeckles; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0007160; P:cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl.
DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0048289; P:isotype switching to IgE isotypes; IEA:Ensembl.
DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; NAS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:0048294; P:negative regulation of isotype switching to IgE isotypes; IEA:Ensembl.
DR GO; GO:0070664; P:negative regulation of leukocyte proliferation; IEA:Ensembl.
DR GO; GO:0032764; P:negative regulation of mast cell cytokine production; IEA:Ensembl.
DR GO; GO:1903464; P:negative regulation of mitotic cell cycle DNA replication; NAS:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:1900099; P:negative regulation of plasma cell differentiation; IEA:Ensembl.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IEA:Ensembl.
DR GO; GO:0045629; P:negative regulation of T-helper 2 cell differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0002317; P:plasma cell differentiation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IEA:Ensembl.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IMP:ARUK-UCL.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0021859; P:pyramidal neuron differentiation; IEA:Ensembl.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0001817; P:regulation of cytokine production; IBA:GO_Central.
DR GO; GO:0002634; P:regulation of germinal center formation; NAS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0050776; P:regulation of immune response; NAS:UniProtKB.
DR GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR GO; GO:0043380; P:regulation of memory T cell differentiation; IEA:Ensembl.
DR GO; GO:0042129; P:regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007266; P:Rho protein signal transduction; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0045064; P:T-helper 2 cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0042092; P:type 2 immune response; IBA:GO_Central.
DR Gene3D; 3.30.710.10; -; 1.
DR IDEAL; IID00372; -.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00355; ZnF_C2H2; 6.
DR SUPFAM; SSF54695; SSF54695; 1.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing;
KW Chromosomal rearrangement; DNA-binding; Immunity; Inflammatory response;
KW Metal-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..706
FT /note="B-cell lymphoma 6 protein"
FT /id="PRO_0000047098"
FT DOMAIN 32..99
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT ZN_FING 518..541
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 546..568
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 574..596
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 602..624
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 630..652
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 658..681
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 317..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..379
FT /note="Required for interaction with NuRD complex and for
FT transcriptional repressor activity"
FT REGION 407..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 326..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..467
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 333
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:9649500,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 343
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:9649500"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41183"
FT MOD_RES 379
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:12402037"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41183"
FT VAR_SEQ 514..569
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_042709"
FT VARIANT 252
FT /note="N -> S (in dbSNP:rs34463990)"
FT /id="VAR_052709"
FT VARIANT 493
FT /note="A -> T (in dbSNP:rs2229362)"
FT /id="VAR_019970"
FT VARIANT 676
FT /note="H -> Y (in dbSNP:rs1056936)"
FT /id="VAR_014825"
FT MUTAGEN 21
FT /note="N->K: Abolishes interaction with NCOR2 and HDAC2, no
FT effect on interaction with CTBP1 and transcriptional
FT autoinhibition; when associated with A-116 and 376-Q--Q-
FT 379."
FT /evidence="ECO:0000269|PubMed:18212045"
FT MUTAGEN 59
FT /note="S->A: Abolished ubiquitination by the SCF(FBXL17)
FT complex."
FT /evidence="ECO:0000269|PubMed:30190310"
FT MUTAGEN 116
FT /note="H->A: Abolishes interaction with NCOR2 and HDAC2, no
FT effect on interaction with CTBP1 and transcriptional
FT autoinhibition; when associated with K-21 and 376-Q--Q-
FT 379."
FT /evidence="ECO:0000269|PubMed:18212045"
FT MUTAGEN 190
FT /note="T->A: No effect on interaction with PIN1."
FT /evidence="ECO:0000269|PubMed:17828269"
FT MUTAGEN 250
FT /note="S->A: No effect on interaction with PIN1."
FT /evidence="ECO:0000269|PubMed:17828269"
FT MUTAGEN 260
FT /note="S->A: Strongly reduces interaction with PIN1."
FT /evidence="ECO:0000269|PubMed:17828269"
FT MUTAGEN 333
FT /note="S->A: Decrease in phosphorylation by MAPK1."
FT /evidence="ECO:0000269|PubMed:9649500"
FT MUTAGEN 343
FT /note="S->A: Decrease in phosphorylation by MAPK1."
FT /evidence="ECO:0000269|PubMed:9649500"
FT MUTAGEN 376..379
FT /note="KKYK->QQYQ: Abolishes interaction with HDAC2 and
FT MTA3 as well as transcriptional repressor and transforming
FT activities. Abolishes interaction with NCOR2 and HDAC2, no
FT effect on interaction with CTBP1 and transcriptional
FT autoinhibition; when associated with K-21 and A-116."
FT /evidence="ECO:0000269|PubMed:15454082,
FT ECO:0000269|PubMed:18212045"
FT MUTAGEN 376
FT /note="K->R: No effect on acetylation."
FT /evidence="ECO:0000269|PubMed:12402037"
FT MUTAGEN 377
FT /note="K->R: No effect on acetylation."
FT /evidence="ECO:0000269|PubMed:12402037"
FT MUTAGEN 379
FT /note="K->R: Abolishes acetylation. No effect on
FT interaction with MTA3, NCOR1 and NCOR2."
FT /evidence="ECO:0000269|PubMed:12402037,
FT ECO:0000269|PubMed:15454082"
FT MUTAGEN 520..523
FT /note="CNEC->GNEG: No effect on DNA-binding, nuclear
FT localization, transcriptional repression activity and
FT interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT MUTAGEN 548..551
FT /note="CDRC->GDRG: No effect on DNA-binding, nuclear
FT localization, transcriptional repression activity and
FT interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT MUTAGEN 576..579
FT /note="CNIC->GNIG: Abolishes DNA-binding and
FT transcriptional repression activity, no effect on nuclear
FT localization and interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT MUTAGEN 604..607
FT /note="CETC->GETG: Abolishes DNA-binding and
FT transcriptional repression activity, perturbs nuclear
FT localization. No effect on interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT MUTAGEN 632..635
FT /note="CEIC->GEIG: Abolishes DNA-binding and
FT transcriptional repression activity, no effect on nuclear
FT localization and interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT MUTAGEN 660..663
FT /note="CEKC->GEKG: Abolishes DNA-binding and
FT transcriptional repression activity, perturbs nuclear
FT localization. No effect on interaction with HDAC5."
FT /evidence="ECO:0000269|PubMed:12504096"
FT CONFLICT 347
FT /note="S -> A (in Ref. 2; AAC50054)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="E -> G (in Ref. 2; AAC50054)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="P -> A (in Ref. 2; AAC50054)"
FT /evidence="ECO:0000305"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:6XZZ"
FT HELIX 14..27
FT /evidence="ECO:0007829|PDB:7OKL"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:3E4U"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:7OKL"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 47..53
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 55..62
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:7OKL"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 80..92
FT /evidence="ECO:0007829|PDB:7OKL"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:6XYX"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:7OKL"
FT HELIX 115..127
FT /evidence="ECO:0007829|PDB:7OKL"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:2YRM"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:2YRM"
FT HELIX 530..540
FT /evidence="ECO:0007829|PDB:2YRM"
FT HELIX 558..568
FT /evidence="ECO:0007829|PDB:2LCE"
FT STRAND 573..575
FT /evidence="ECO:0007829|PDB:2LCE"
FT TURN 577..579
FT /evidence="ECO:0007829|PDB:2LCE"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:2LCE"
FT HELIX 586..596
FT /evidence="ECO:0007829|PDB:2LCE"
FT STRAND 601..603
FT /evidence="ECO:0007829|PDB:2EN2"
FT TURN 605..607
FT /evidence="ECO:0007829|PDB:2EN2"
FT STRAND 610..613
FT /evidence="ECO:0007829|PDB:2EN2"
FT HELIX 614..620
FT /evidence="ECO:0007829|PDB:2EN2"
FT HELIX 622..625
FT /evidence="ECO:0007829|PDB:2EN2"
FT STRAND 633..635
FT /evidence="ECO:0007829|PDB:2EOS"
FT STRAND 639..641
FT /evidence="ECO:0007829|PDB:2EOS"
FT HELIX 642..648
FT /evidence="ECO:0007829|PDB:2EOS"
FT TURN 649..652
FT /evidence="ECO:0007829|PDB:2EOS"
SQ SEQUENCE 706 AA; 78846 MW; E38D83C213DAE2D0 CRC64;
MASPADSCIQ FTRHASDVLL NLNRLRSRDI LTDVVIVVSR EQFRAHKTVL MACSGLFYSI
FTDQLKCNLS VINLDPEINP EGFCILLDFM YTSRLNLREG NIMAVMATAM YLQMEHVVDT
CRKFIKASEA EMVSAIKPPR EEFLNSRMLM PQDIMAYRGR EVVENNLPLR SAPGCESRAF
APSLYSGLST PPASYSMYSH LPVSSLLFSD EEFRDVRMPV ANPFPKERAL PCDSARPVPG
EYSRPTLEVS PNVCHSNIYS PKETIPEEAR SDMHYSVAEG LKPAAPSARN APYFPCDKAS
KEEERPSSED EIALHFEPPN APLNRKGLVS PQSPQKSDCQ PNSPTESCSS KNACILQASG
SPPAKSPTDP KACNWKKYKF IVLNSLNQNA KPEGPEQAEL GRLSPRAYTA PPACQPPMEP
ENLDLQSPTK LSASGEDSTI PQASRLNNIV NRSMTGSPRS SSESHSPLYM HPPKCTSCGS
QSPQHAEMCL HTAGPTFPEE MGETQSEYSD SSCENGAFFC NECDCRFSEE ASLKRHTLQT
HSDKPYKCDR CQASFRYKGN LASHKTVHTG EKPYRCNICG AQFNRPANLK THTRIHSGEK
PYKCETCGAR FVQVAHLRAH VLIHTGEKPY PCEICGTRFR HLQTLKSHLR IHTGEKPYHC
EKCNLHFRHK SQLRLHLRQK HGAITNTKVQ YRVSATDLPP ELPKAC
