| UniProt ID | BCL6_HUMAN | |
|---|---|---|
| UniProt AC | P41182 | |
| Protein Name | B-cell lymphoma 6 protein | |
| Gene Name | BCL6 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 706 | |
| Subcellular Localization | Nucleus . | |
| Protein Description | 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.. | |
| Protein Sequence | MASPADSCIQFTRHASDVLLNLNRLRSRDILTDVVIVVSREQFRAHKTVLMACSGLFYSIFTDQLKCNLSVINLDPEINPEGFCILLDFMYTSRLNLREGNIMAVMATAMYLQMEHVVDTCRKFIKASEAEMVSAIKPPREEFLNSRMLMPQDIMAYRGREVVENNLPLRSAPGCESRAFAPSLYSGLSTPPASYSMYSHLPVSSLLFSDEEFRDVRMPVANPFPKERALPCDSARPVPGEYSRPTLEVSPNVCHSNIYSPKETIPEEARSDMHYSVAEGLKPAAPSARNAPYFPCDKASKEEERPSSEDEIALHFEPPNAPLNRKGLVSPQSPQKSDCQPNSPTESCSSKNACILQASGSPPAKSPTDPKACNWKKYKFIVLNSLNQNAKPEGPEQAELGRLSPRAYTAPPACQPPMEPENLDLQSPTKLSASGEDSTIPQASRLNNIVNRSMTGSPRSSSESHSPLYMHPPKCTSCGSQSPQHAEMCLHTAGPTFPEEMGETQSEYSDSSCENGAFFCNECDCRFSEEASLKRHTLQTHSDKPYKCDRCQASFRYKGNLASHKTVHTGEKPYRCNICGAQFNRPANLKTHTRIHSGEKPYKCETCGARFVQVAHLRAHVLIHTGEKPYPCEICGTRFRHLQTLKSHLRIHTGEKPYHCEKCNLHFRHKSQLRLHLRQKHGAITNTKVQYRVSATDLPPELPKAC | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 3 | Phosphorylation | -----MASPADSCIQ -----CCCHHHHHHH | 21.23 | 28348404 | |
| 39 | Phosphorylation | TDVVIVVSREQFRAH CCEEEEEEHHHHHHH | 21.14 | 24719451 | |
| 157 | Phosphorylation | MPQDIMAYRGREVVE CHHHHHHHCCHHHHH | 9.02 | 26434552 | |
| 243 | Phosphorylation | RPVPGEYSRPTLEVS CCCCCCCCCCEEEEC | 27.73 | 27251275 | |
| 246 | Phosphorylation | PGEYSRPTLEVSPNV CCCCCCCEEEECCCC | 34.15 | 27251275 | |
| 250 | Phosphorylation | SRPTLEVSPNVCHSN CCCEEEECCCCCCCC | 11.03 | 25159151 | |
| 256 | Phosphorylation | VSPNVCHSNIYSPKE ECCCCCCCCCCCCCC | 21.57 | 23312004 | |
| 259 | Phosphorylation | NVCHSNIYSPKETIP CCCCCCCCCCCCCCC | 24.15 | 23312004 | |
| 260 | Phosphorylation | VCHSNIYSPKETIPE CCCCCCCCCCCCCCH | 26.21 | 25159151 | |
| 271 | Phosphorylation | TIPEEARSDMHYSVA CCCHHHHHHCCHHHH | 46.46 | 28674151 | |
| 282 | Ubiquitination | YSVAEGLKPAAPSAR HHHHCCCCCCCCCCC | 43.39 | 2190698 | |
| 298 | Ubiquitination | APYFPCDKASKEEER CCCCCCCCCCCCCCC | 62.37 | - | |
| 300 | Phosphorylation | YFPCDKASKEEERPS CCCCCCCCCCCCCCC | 46.47 | 28857561 | |
| 307 | Phosphorylation | SKEEERPSSEDEIAL CCCCCCCCCCCCEEH | 53.21 | 30266825 | |
| 308 | Phosphorylation | KEEERPSSEDEIALH CCCCCCCCCCCEEHC | 52.31 | 30266825 | |
| 330 | Phosphorylation | LNRKGLVSPQSPQKS CCCCCCCCCCCCCCC | 23.43 | 30266825 | |
| 333 | Phosphorylation | KGLVSPQSPQKSDCQ CCCCCCCCCCCCCCC | 32.46 | 23401153 | |
| 337 | Phosphorylation | SPQSPQKSDCQPNSP CCCCCCCCCCCCCCC | 38.07 | 28450419 | |
| 343 | Phosphorylation | KSDCQPNSPTESCSS CCCCCCCCCCCCCCC | 39.62 | 27794612 | |
| 345 | Phosphorylation | DCQPNSPTESCSSKN CCCCCCCCCCCCCCC | 40.11 | 30576142 | |
| 347 | Phosphorylation | QPNSPTESCSSKNAC CCCCCCCCCCCCCEE | 23.06 | 28450419 | |
| 349 | Phosphorylation | NSPTESCSSKNACIL CCCCCCCCCCCEEEE | 54.34 | 28450419 | |
| 350 | Phosphorylation | SPTESCSSKNACILQ CCCCCCCCCCEEEEE | 33.97 | 28450419 | |
| 359 | Phosphorylation | NACILQASGSPPAKS CEEEEEECCCCCCCC | 27.17 | 30266825 | |
| 361 | Phosphorylation | CILQASGSPPAKSPT EEEEECCCCCCCCCC | 25.80 | 30266825 | |
| 366 | Phosphorylation | SGSPPAKSPTDPKAC CCCCCCCCCCCCCCC | 34.83 | 30278072 | |
| 368 | Phosphorylation | SPPAKSPTDPKACNW CCCCCCCCCCCCCCC | 72.52 | 23663014 | |
| 371 | Ubiquitination | AKSPTDPKACNWKKY CCCCCCCCCCCCCEE | 69.27 | - | |
| 379 | Acetylation | ACNWKKYKFIVLNSL CCCCCEEEEEEEECC | 37.18 | 12402037 | |
| 385 | Phosphorylation | YKFIVLNSLNQNAKP EEEEEEECCCCCCCC | 25.24 | 29978859 | |
| 404 | Phosphorylation | QAELGRLSPRAYTAP HHHHHCCCCCCCCCC | 15.81 | 30266825 | |
| 427 | Phosphorylation | PENLDLQSPTKLSAS CCCCCCCCCCCCCCC | 41.66 | 29255136 | |
| 429 | Phosphorylation | NLDLQSPTKLSASGE CCCCCCCCCCCCCCC | 50.27 | 29255136 | |
| 434 | Phosphorylation | SPTKLSASGEDSTIP CCCCCCCCCCCCCCC | 39.06 | 22210691 | |
| 457 | Phosphorylation | VNRSMTGSPRSSSES HCHHCCCCCCCCCCC | 14.15 | 28985074 | |
| 460 | Phosphorylation | SMTGSPRSSSESHSP HCCCCCCCCCCCCCC | 41.42 | 25954137 | |
| 461 | Phosphorylation | MTGSPRSSSESHSPL CCCCCCCCCCCCCCC | 39.13 | 27732954 | |
| 462 | Phosphorylation | TGSPRSSSESHSPLY CCCCCCCCCCCCCCC | 44.35 | 27732954 | |
| 464 | Phosphorylation | SPRSSSESHSPLYMH CCCCCCCCCCCCCCC | 31.08 | 26055452 | |
| 466 | Phosphorylation | RSSSESHSPLYMHPP CCCCCCCCCCCCCCC | 26.36 | 25954137 | |
| 469 | Phosphorylation | SESHSPLYMHPPKCT CCCCCCCCCCCCCCC | 9.21 | 27732954 | |
| 569 | Phosphorylation | ASHKTVHTGEKPYRC CCCCEEECCCCCEEC | 42.58 | - | |
| 572 | Ubiquitination | KTVHTGEKPYRCNIC CEEECCCCCEECCCC | 49.01 | - | |
| 574 | Phosphorylation | VHTGEKPYRCNICGA EECCCCCEECCCCCC | 38.57 | - | |
| 597 | Phosphorylation | KTHTRIHSGEKPYKC CCCCEECCCCCCEEC | 46.40 | 29496963 | |
| 625 | Phosphorylation | RAHVLIHTGEKPYPC EEEEEEECCCCCCCC | 39.79 | - | |
| 653 | Phosphorylation | KSHLRIHTGEKPYHC HHHHEEECCCCCCCC | 44.67 | 28111955 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 333 | S | Phosphorylation | Kinase | ERK2 | P28482 | PSP |
| 333 | S | Phosphorylation | Kinase | MAPK3 | P27361 | GPS |
| 343 | S | Phosphorylation | Kinase | ERK2 | P28482 | PSP |
| 343 | S | Phosphorylation | Kinase | MAPK3 | P27361 | GPS |
| - | K | Ubiquitination | E3 ubiquitin ligase | FBXO11 | Q86XK2 | PMID:22113614 |
| - | K | Ubiquitination | E3 ubiquitin ligase | PELI1 | Q96FA3 | PMID:25295537 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of BCL6_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Antigen receptor signaling induces MAP kinase-mediatedphosphorylation and degradation of the BCL-6 transcription factor."; Niu H., Ye B.H., Dalla-Favera R.; Genes Dev. 12:1953-1961(1998). Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-333 AND SER-343,MUTAGENESIS OF SER-333 AND SER-343, AND UBIQUITINATION. | |
