Homo sapiens Protein: BCL6 | |||||||||||||||||||||||
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Summary | |||||||||||||||||||||||
InnateDB Protein | IDBP-69351.6 | ||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||
Gene Symbol | BCL6 | ||||||||||||||||||||||
Protein Name | B-cell CLL/lymphoma 6 | ||||||||||||||||||||||
Synonyms | BCL5; BCL6A; LAZ3; ZBTB27; ZNF51; | ||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||
Ensembl Protein | ENSP00000232014 | ||||||||||||||||||||||
InnateDB Gene | IDBG-69349 (BCL6) | ||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||
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. {ECO:0000269PubMed:10981963, ECO:0000269PubMed:12402037, ECO:0000269PubMed:12414651, ECO:0000269PubMed:12504096, ECO:0000269PubMed:15454082, ECO:0000269PubMed:15577913, ECO:0000269PubMed:16142238, ECO:0000269PubMed:17828269, ECO:0000269PubMed:18212045, ECO:0000269PubMed:18280243, ECO:0000269PubMed:22113614, ECO:0000269PubMed:23166356, ECO:0000269PubMed:23911289, ECO:0000269PubMed:9649500}. | ||||||||||||||||||||||
Subcellular Localization | Nucleus {ECO:0000269PubMed:12504096, ECO:0000269PubMed:17828269, ECO:0000269PubMed:22113614, ECO:0000269PubMed:23166356}. | ||||||||||||||||||||||
Disease Associations | Note=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.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.Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF. | ||||||||||||||||||||||
Tissue Specificity | Expressed in germinal center T- and B-cells and in primary immature dendritic cells. {ECO:0000269PubMed:10981963, ECO:0000269PubMed:12402037, ECO:0000269PubMed:15454082, ECO:0000269PubMed:16142238, ECO:0000269PubMed:16455075, ECO:0000269PubMed:17828269, ECO:0000269PubMed:18212045, ECO:0000269PubMed:9649500}. | ||||||||||||||||||||||
Comments | |||||||||||||||||||||||
Interactions | |||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 201 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||
InterPro |
IPR000210
BTB/POZ-like IPR007087 Zinc finger, C2H2 IPR011333 BTB/POZ fold IPR013069 BTB/POZ IPR015880 Zinc finger, C2H2-like |
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PFAM |
PF00096
PF00651 |
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PRINTS | |||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||
SMART |
SM00225
SM00355 |
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TIGRFAMs | |||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||
Modification | |||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||
SwissProt | P41182 | ||||||||||||||||||||||
PhosphoSite | PhosphoSite-P41182 | ||||||||||||||||||||||
TrEMBL | C9JL16 | ||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||
Entrez Gene | 604 | ||||||||||||||||||||||
UniGene | Hs.711290 | ||||||||||||||||||||||
RefSeq | NP_001124317 | ||||||||||||||||||||||
HUGO | HGNC:1001 | ||||||||||||||||||||||
OMIM | 109565 | ||||||||||||||||||||||
CCDS | CCDS3289 | ||||||||||||||||||||||
HPRD | 00180 | ||||||||||||||||||||||
IMGT | |||||||||||||||||||||||
EMBL | AC072022 BC150184 CH471052 EU139066 S67779 U00115 Z21943 | ||||||||||||||||||||||
GenPept | AAC50054 AAI50185 ABX45135 CAA79937 EAW78140 EAW78141 | ||||||||||||||||||||||