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Protein

B-cell lymphoma 6 protein homolog

Gene

Bcl6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri519 – 542C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri547 – 569C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri575 – 597C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri603 – 625C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri631 – 653C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri659 – 682C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processImmunity, Inflammatory response, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
B-cell lymphoma 6 protein homolog
Gene namesi
Name:Bcl6
Synonyms:Bcl-6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:107187 Bcl6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

More than 50% of lethality by 6 weeks of age. Mice have infiltrates of inflammatory cells in their lungs, as well as multinodular lesions with eosinophil infiltrations into the spleen, significantly more T(H)2 and T(H)17 cells and up-regulated levels of inflammtaroy chemokines in macrophages, but, express low levels of memory CD8+ T-cells and, in spleen, GC B and T(FH) cells are both undetectable. B-cells express 10-fold lower levels of surface IgM than control littermates and macrophages divide faster. From 12.5 dpc to at least 21 days after birth, animals have reduced size of the cerebral hemispheres and a reduced thickness of the frontal and parietal cortex with all the cortical layers affected. At 12.5 and 15.5 dpc, marked reduction of cell-cyle exit indicating defective transition from neural progenitor Cells to postmitotic neurons.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi21N → K: Abolishes interaction with NCOR2; mice have impaired GC formation and immunoglobulin affinity maturation with lower proliferation and survival of GC B-cells but normal differentiation of helper T-cell subsets and inflammatory response; in macrophages, no effect on transcriptional repression of genes encoding inflammatory molecules; when associated with A-116. In macrophages, no effect on competition with STAT5 for DNA-binding and transcriptional repression of genes encoding inflammatory molecules; when associated with A-116 and 377-Q--Q-380. 2 Publications1
Mutagenesisi116H → A: Abolishes interaction with NCOR2; mice have impaired GC formation and immunoglobulin affinity maturation with lower proliferation and survival of GC B-cells but normal differentiation of helper T-cell subsets and inflammatory response; in macrophages, no effect on transcriptional repression of genes encoding inflammatory molecules; when associated with K-21. In macrophages, no effect on competition with STAT5 for DNA-binding and transcriptional repression of genes encoding inflammatory molecules; when associated with K-21 and 377-Q--Q-380. 2 Publications1
Mutagenesisi377 – 380KKYK → QQYQ in macrophages, no effect on transcriptional repression of genes encoding inflammatory molecules. In macrophages, no effect on competition with STAT5 for DNA-binding and transcriptional repression of genes encoding inflammatory molecules; when associated with K-21 and A-116. 1 Publication4
Mutagenesisi577 – 580CNIC → GNIG in macrophages, inhibits competition with STAT5 for DNA-binding and abolishes transcriptional repression of genes encoding inflammatory molecules. 1 Publication4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000470991 – 707B-cell lymphoma 6 protein homologAdd BLAST707

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei334PhosphoserineCombined sources1
Modified residuei344Phosphoserine; by MAPK1By similarity1
Modified residuei362PhosphoserineCombined sources1
Modified residuei380N6-acetyllysine; by EP300By similarity1
Modified residuei405PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-334 and Ser-344. Phosphorylated by ATM in response to genotoxic stress. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.By similarity
Polyubiquitinated. Polyubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome. Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteaseome: ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB domain dimers are formed.By similarity
Acetylated at Lys-380 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function. Deacetylated by HDAC- and SIR2-dependent pathways.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP41183
PRIDEiP41183

PTM databases

iPTMnetiP41183
PhosphoSitePlusiP41183

Expressioni

Tissue specificityi

Expressed at least in germinal center B-cells of spleen.2 Publications

Developmental stagei

Detected in the cerebral cortex from 12.5 dpc until birth, with highest levels in the frontal and parietal parts of the neocortex than the occipital parts.1 Publication

Gene expression databases

BgeeiENSMUSG00000022508 Expressed in 292 organ(s), highest expression level in skin of back
CleanExiMM_BCL6
ExpressionAtlasiP41183 baseline and differential
GenevisibleiP41183 MM

Interactioni

Subunit structurei

Homodimer. Interacts (via BTB domain) with the corepressors BCOR, NCOR1 and SMRT/NCOR2; the interactions are direct. Forms preferably ternary complexes with BCOR and SMRT/NCOR2 on target gene promoters but, on enhancer elements, interacts with SMRT/NCOR2 and HDAC3 to repress proximal gene expression. Interacts with histone deacetylases HDAC2, HDAC5 and HDAC9 (via the catalytic domain). Interacts with ZBTB7 and BCL6B. Interacts with SCF(FBXO11) complex; the interaction is independent of phosphorylation and promotes ubiquitination. Interacts (when phosphorylated) with PIN1; the interaction is required for BCL6 degradation upon genotoxic stress. Interacts with ZBTB17; inhibits ZBTB17 transcriptional activity. Interacts with CTBP1, autoinhibits its transcriptional expression. Interacts with NOTCH1 NCID and SIRT1; leads to a epigenetic repression of selective NOTCH1-target genes. Interacts (nor via BTB domain neither acetylated) with the NuRD complex components CHD4, HDAC1, MBD3 and MTA3; the interaction with MTA3 inhibits BCL6 acetylation and is required for BCL6 transpriptional repression.4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198327, 8 interactors
DIPiDIP-59432N
IntActiP41183, 4 interactors
STRINGi10090.ENSMUSP00000023151

Structurei

3D structure databases

ProteinModelPortaliP41183
SMRiP41183
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 99BTBPROSITE-ProRule annotationAdd BLAST68

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni377 – 380Required for interaction with NuRD complex and for transcriptional repressor activity4

Domaini

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 differentiation required for GC formation.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri519 – 542C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri547 – 569C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri575 – 597C2H2-type 3PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri603 – 625C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri631 – 653C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri659 – 682C2H2-type 6PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00930000150977
HOGENOMiHOG000001556
HOVERGENiHBG004831
InParanoidiP41183
KOiK15618
OMAiTEMCLHT
OrthoDBiEOG091G025U
PhylomeDBiP41183
TreeFamiTF330912

Family and domain databases

InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR011333 SKP1/BTB/POZ_sf
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00651 BTB, 1 hit
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SM00355 ZnF_C2H2, 6 hits
SUPFAMiSSF54695 SSF54695, 1 hit
SSF57667 SSF57667, 4 hits
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 6 hits
PS50157 ZINC_FINGER_C2H2_2, 6 hits

Sequencei

Sequence statusi: Complete.

P41183-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASPADSCIQ FTRHASDVLL NLNRLRSRDI LTDVVIVVSR EQFRAHKTVL
60 70 80 90 100
MACSGLFYSI FTDQLKCNLS VINLDPEISP EGFCILLDFM YTSRLNLREG
110 120 130 140 150
NIMAVMTTAM YLQMEHVVDT CRKFIKASEA EMAPALKPPR EEFLNSRMLM
160 170 180 190 200
PHDIMAYRGR EVVENNMPLR NTPGCESRAF APPLYSGLST PPASYPMYSH
210 220 230 240 250
LPLSTFLFSD EELRDAPRMP VANPFPKERA LPCDSARQVP NEYSRPAMEV
260 270 280 290 300
SPSLCHSNIY SPKEAVPEEA RSDIHYSVPE GPKPAVPSAR NAPYFPCDKA
310 320 330 340 350
SKEEERPSSE DEIALHFEPP NAPLNRKGLV SPQSPQKSDC QPNSPTESCS
360 370 380 390 400
SKNACILQAS GSPPAKSPTD PKACNWKKYK FIVLNSLNQN AKPEGSEQAE
410 420 430 440 450
LGRLSPRAYP APPACQPPME PANLDLQSPT KLSASGEDST IPQASRLNNL
460 470 480 490 500
VNRSLAGSPR SSSESHSPLY MHPPKCTSCG SQSPQHTEMC LHTAGPTFPE
510 520 530 540 550
EMGETQSEYS DSSCENGTFF CNECDCRFSE EASLKRHTLQ THSDKPYKCD
560 570 580 590 600
RCQASFRYKG NLASHKTVHT GEKPYRCNIC GAQFNRPANL KTHTRIHSGE
610 620 630 640 650
KPYKCETCGA RFVQVAHLRA HVLIHTGEKP YPCEICGTRF RHLQTLKSHL
660 670 680 690 700
RIHTGEKPYH CEKCNLHFRH KSQLRLHLRQ KHGAITNTKV QYRVSAADLP

PELPKAC
Length:707
Mass (Da):78,982
Last modified:February 1, 1995 - v1
Checksum:i2051DD808D32D5EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti456A → G in AAB17432 (PubMed:8652841).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38377 mRNA Translation: BAA07456.1
U41465 mRNA Translation: AAB17432.1
BC052315 mRNA Translation: AAH52315.1
CCDSiCCDS28082.1
RefSeqiNP_001334955.1, NM_001348026.1
NP_033874.1, NM_009744.4
XP_017172344.1, XM_017316855.1
UniGeneiMm.347398

Genome annotation databases

EnsembliENSMUST00000023151; ENSMUSP00000023151; ENSMUSG00000022508
GeneIDi12053
KEGGimmu:12053
UCSCiuc007ytz.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38377 mRNA Translation: BAA07456.1
U41465 mRNA Translation: AAB17432.1
BC052315 mRNA Translation: AAH52315.1
CCDSiCCDS28082.1
RefSeqiNP_001334955.1, NM_001348026.1
NP_033874.1, NM_009744.4
XP_017172344.1, XM_017316855.1
UniGeneiMm.347398

3D structure databases

ProteinModelPortaliP41183
SMRiP41183
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198327, 8 interactors
DIPiDIP-59432N
IntActiP41183, 4 interactors
STRINGi10090.ENSMUSP00000023151

PTM databases

iPTMnetiP41183
PhosphoSitePlusiP41183

Proteomic databases

PaxDbiP41183
PRIDEiP41183

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023151; ENSMUSP00000023151; ENSMUSG00000022508
GeneIDi12053
KEGGimmu:12053
UCSCiuc007ytz.1 mouse

Organism-specific databases

CTDi604
MGIiMGI:107187 Bcl6

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00930000150977
HOGENOMiHOG000001556
HOVERGENiHBG004831
InParanoidiP41183
KOiK15618
OMAiTEMCLHT
OrthoDBiEOG091G025U
PhylomeDBiP41183
TreeFamiTF330912

Miscellaneous databases

ChiTaRSiBcl6 mouse
PROiPR:P41183
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022508 Expressed in 292 organ(s), highest expression level in skin of back
CleanExiMM_BCL6
ExpressionAtlasiP41183 baseline and differential
GenevisibleiP41183 MM

Family and domain databases

InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR011333 SKP1/BTB/POZ_sf
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00651 BTB, 1 hit
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SM00355 ZnF_C2H2, 6 hits
SUPFAMiSSF54695 SSF54695, 1 hit
SSF57667 SSF57667, 4 hits
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit
PS00028 ZINC_FINGER_C2H2_1, 6 hits
PS50157 ZINC_FINGER_C2H2_2, 6 hits
ProtoNetiSearch...

Entry informationi

Entry nameiBCL6_MOUSE
AccessioniPrimary (citable) accession number: P41183
Secondary accession number(s): Q61065
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 7, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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