Human Gene BCL6 (uc003frp.3)
  Description: Homo sapiens B-cell CLL/lymphoma 6 (BCL6), transcript variant 2, mRNA.
RefSeq Summary (NM_001130845): The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015].
Transcript (Including UTRs)
   Position: hg19 chr3:187,439,165-187,454,285 Size: 15,121 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr3:187,440,246-187,451,481 Size: 11,236 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:187,439,165-187,454,285)mRNA (may differ from genome)Protein (706 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHuman Cortex Gene ExpressionLynxMalacards
MGIneXtProtOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: BCL6_HUMAN
DESCRIPTION: RecName: Full=B-cell lymphoma 6 protein; Short=BCL-6; AltName: Full=B-cell lymphoma 5 protein; Short=BCL-5; AltName: Full=Protein LAZ-3; AltName: Full=Zinc finger and BTB domain-containing protein 27; AltName: Full=Zinc finger protein 51;
FUNCTION: Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.
SUBUNIT: Homodimer. Interacts (via BTB domain) with BCOR; the interaction is direct. Interacts (via BTB domain) with NCOR2; the interaction is direct. Interacts with ZBTB7 and BCL6B (By similarity). Interacts with the catalytic domain of HDAC9.
INTERACTION: P56524:HDAC4; NbExp=3; IntAct=EBI-765407, EBI-308629; Q9UKV0:HDAC9; NbExp=2; IntAct=EBI-765407, EBI-765444; Q9ULU4:ZMYND8; NbExp=3; IntAct=EBI-765407, EBI-765834;
SUBCELLULAR LOCATION: Nucleus (By similarity).
TISSUE SPECIFICITY: Expressed in germinal center T and B-cells and in primary immature dendritic cells.
INDUCTION: Down-regulated during maturation of dendritic cells by selective stimuli such as bacterial lipopolysaccharides (LPS), CD40LG and zymosan.
DOMAIN: The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2.
PTM: Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-333 and Ser-343. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.
PTM: Polyubiquitinated. Polyubiquitination leads to degradation by the proteasome.
DISEASE: Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions.
DISEASE: Note=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.
DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
SIMILARITY: Contains 1 BTB (POZ) domain.
SIMILARITY: Contains 6 C2H2-type zinc fingers.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BCL6ID20.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): BCL6
CDC HuGE Published Literature: BCL6
Positive Disease Associations: Blood Urea Nitrogen , Cell Adhesion Molecules , Cholesterol, HDL , Eosinophils , follicle center lymphoma , follicular lymphoma , Lipoproteins, HDL , lymphoma, follicle center , Platelet Count , Waldenstrom macroglobulinaemia
Related Studies:
  1. Blood Urea Nitrogen
    Yoichiro Kamatani et al. Nature genetics 2010, Genome-wide association study of hematological and biochemical traits in a Japanese population., Nature genetics. [PubMed 20139978]
  2. Blood Urea Nitrogen
    Young Jin Kim et al. Nature genetics 2011, Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits., Nature genetics. [PubMed 21909109]
  3. Cell Adhesion Molecules
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: BCL6
Diseases sorted by gene-association score: primary mediastinal large b-cell lymphoma* (368), intravascular large b-cell lymphoma* (368), follicular lymphoma 1* (202), b-cell lymphomas* (152), lymphoma (79), diffuse large b-cell lymphoma (41), hodgkin lymphoma (39), marginal zone b-cell lymphoma (37), primary effusion lymphoma (37), gastric lymphoma (30), follicular lymphoma (28), angioimmunoblastic t-cell lymphoma (26), lymphosarcoma (23), burkitt lymphoma (21), primary central nervous system lymphoma (19), nodular lymphocyte predominant hodgkin lymphoma (19), t-cell/histiocyte rich large b cell lymphoma (19), primary cutaneous cd4+ small/medium-sized pleomorphic t-cell lymphoma (19), nodal marginal zone b-cell lymphoma (19), plasmablastic lymphoma (18), central nervous system lymphoma (18), idiopathic cd4-positive t-lymphocytopenia (16), reticulosarcoma (15), microphthalmia, syndromic 2 (14), lymphoma, malt, somatic (13), lymphoblastic lymphoma (13), intraocular lymphoma (13), mantle cell lymphoma (12), peripheral t-cell lymphoma (11), b-cell lymphoma of mucosa-associated lymphoid tissue (11), heart lymphoma (10), lymphoma, non-hodgkin (10), splenic marginal zone lymphoma (10), lymphatic system cancer (10), mature b-cell neoplasm (9), bone lymphoma (9), breast lymphoma (8), testicular lymphoma (8), colon lymphoma (7), epidural neoplasm (7), composite lymphoma (6), human herpesvirus 8 (6), multicentric castleman disease (6), mediastinal malignant lymphoma (4), chronic lymphocytic leukemia (4), mediastinal gray zone lymphoma (4), immunodeficiency with hyper-igm, type 2 (4), lung lymphoma (4), acquired immunodeficiency syndrome (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 189.48 RPKM in Whole Blood
Total median expression: 2367.95 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -142.94457-0.313 Picture PostScript Text
3' UTR -283.481081-0.262 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000210 - BTB/POZ-like
IPR011333 - BTB/POZ_fold
IPR013069 - BTB_POZ
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00096 - Zinc finger, C2H2 type
PF00651 - BTB/POZ domain
PF12874 - Zinc-finger of C2H2 type
PF13912 - C2H2-type zinc finger

SCOP Domains:
48695 - Multiheme cytochromes
54695 - POZ domain
57667 - C2H2 and C2HC zinc fingers

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1R28 - X-ray MuPIT 1R29 - X-ray MuPIT 1R2B - X-ray MuPIT 2EN2 - NMR MuPIT 2EOS - NMR MuPIT 2LCE - NMR MuPIT 2YRM - NMR MuPIT 3BIM - X-ray MuPIT 3E4U - X-ray MuPIT 3LBZ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P41182
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001161 intronic transcription regulatory region sequence-specific DNA binding
GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0031490 chromatin DNA binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0000060 protein import into nucleus, translocation
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000902 cell morphogenesis
GO:0001953 negative regulation of cell-matrix adhesion
GO:0002376 immune system process
GO:0002467 germinal center formation
GO:0002634 regulation of germinal center formation
GO:0002829 negative regulation of type 2 immune response
GO:0002903 negative regulation of B cell apoptotic process
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006954 inflammatory response
GO:0006974 cellular response to DNA damage stimulus
GO:0007266 Rho protein signal transduction
GO:0007283 spermatogenesis
GO:0008104 protein localization
GO:0008285 negative regulation of cell proliferation
GO:0019221 cytokine-mediated signaling pathway
GO:0030036 actin cytoskeleton organization
GO:0030183 B cell differentiation
GO:0030308 negative regulation of cell growth
GO:0030890 positive regulation of B cell proliferation
GO:0031065 positive regulation of histone deacetylation
GO:0032764 negative regulation of mast cell cytokine production
GO:0035024 negative regulation of Rho protein signal transduction
GO:0042092 type 2 immune response
GO:0042127 regulation of cell proliferation
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043087 regulation of GTPase activity
GO:0043380 regulation of memory T cell differentiation
GO:0045591 positive regulation of regulatory T cell differentiation
GO:0045596 negative regulation of cell differentiation
GO:0045629 negative regulation of T-helper 2 cell differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045746 negative regulation of Notch signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0048294 negative regulation of isotype switching to IgE isotypes
GO:0048821 erythrocyte development
GO:0050727 regulation of inflammatory response
GO:0050776 regulation of immune response
GO:0051272 positive regulation of cellular component movement
GO:1903464 negative regulation of mitotic cell cycle DNA replication
GO:2000773 negative regulation of cellular senescence

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005794 Golgi apparatus
GO:0005657 replication fork


-  Descriptions from all associated GenBank mRNAs
  BC142705 - Homo sapiens B-cell CLL/lymphoma 6, mRNA (cDNA clone MGC:165045 IMAGE:40148809), complete cds.
BC150184 - Homo sapiens B-cell CLL/lymphoma 6, mRNA (cDNA clone MGC:164962 IMAGE:40148297), complete cds.
BC146796 - Homo sapiens cDNA clone IMAGE:8860299, containing frame-shift errors.
U00115 - Human zinc-finger protein (bcl-6) mRNA, complete cds.
BX649185 - Homo sapiens mRNA; cDNA DKFZp686M22130 (from clone DKFZp686M22130).
JD394639 - Sequence 375663 from Patent EP1572962.
JD325081 - Sequence 306105 from Patent EP1572962.
JD058934 - Sequence 39958 from Patent EP1572962.
JD524955 - Sequence 505979 from Patent EP1572962.
JD566171 - Sequence 547195 from Patent EP1572962.
JD276886 - Sequence 257910 from Patent EP1572962.
JD561195 - Sequence 542219 from Patent EP1572962.
JD048679 - Sequence 29703 from Patent EP1572962.
Z21943 - H.sapiens mRNA for zinc finger protein.
JD053070 - Sequence 34094 from Patent EP1572962.
JD277183 - Sequence 258207 from Patent EP1572962.
JD426389 - Sequence 407413 from Patent EP1572962.
AK304325 - Homo sapiens cDNA FLJ60220 complete cds, highly similar to B-cell lymphoma 6 protein.
JD088782 - Sequence 69806 from Patent EP1572962.
AK308162 - Homo sapiens cDNA, FLJ98110.
JD386449 - Sequence 367473 from Patent EP1572962.
JD249111 - Sequence 230135 from Patent EP1572962.
S67779 - BCL5=Cys2-His2 zinc-finger transcription factor [human, liver, mRNA, 2600 nt].
JD355294 - Sequence 336318 from Patent EP1572962.
EU139066 - Homo sapiens B-cell lymphoma 6 protein transcript variant (BCL6) mRNA, complete cds.
EU883531 - Homo sapiens zinc finger transcription factor BCL6S (BCL6) mRNA, complete cds, alternatively spliced.
KJ896488 - Synthetic construct Homo sapiens clone ccsbBroadEn_05882 BCL6 gene, encodes complete protein.
KJ905147 - Synthetic construct Homo sapiens clone ccsbBroadEn_14547 BCL6 gene, encodes complete protein.
AB384967 - Synthetic construct DNA, clone: pF1KB4594, Homo sapiens BCL6 gene for B-cell lymphoma 6 protein, complete cds, without stop codon, in Flexi system.
JD501528 - Sequence 482552 from Patent EP1572962.
JD499024 - Sequence 480048 from Patent EP1572962.
JD181345 - Sequence 162369 from Patent EP1572962.
JD252828 - Sequence 233852 from Patent EP1572962.
JD381387 - Sequence 362411 from Patent EP1572962.
JD283828 - Sequence 264852 from Patent EP1572962.
JD386360 - Sequence 367384 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P41182 (Reactome details) participates in the following event(s):

R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes
R-HSA-449147 Signaling by Interleukins
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-212436 Generic Transcription Pathway
R-HSA-168256 Immune System
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A7E241, B8PSA7, BCL5, BCL6_HUMAN, D3DNV5, LAZ3, NM_001130845, NP_001697, P41182, ZBTB27, ZNF51
UCSC ID: uc003frp.3
RefSeq Accession: NM_001130845
Protein: P41182 (aka BCL6_HUMAN)
CCDS: CCDS3289.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001130845.1
exon count: 10CDS single in 3' UTR: no RNA size: 3662
ORF size: 2121CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4268.50frame shift in genome: no % Coverage: 99.92
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.