General Information of Target

Target ID LDTP03925
Target Name B-cell lymphoma 6 protein (BCL6)
Gene Name BCL6
Gene ID 604
Synonyms
BCL5; LAZ3; ZBTB27; ZNF51; B-cell lymphoma 6 protein; BCL-6; B-cell lymphoma 5 protein; BCL-5; Protein LAZ-3; Zinc finger and BTB domain-containing protein 27; Zinc finger protein 51
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASPADSCIQFTRHASDVLLNLNRLRSRDILTDVVIVVSREQFRAHKTVLMACSGLFYSI
FTDQLKCNLSVINLDPEINPEGFCILLDFMYTSRLNLREGNIMAVMATAMYLQMEHVVDT
CRKFIKASEAEMVSAIKPPREEFLNSRMLMPQDIMAYRGREVVENNLPLRSAPGCESRAF
APSLYSGLSTPPASYSMYSHLPVSSLLFSDEEFRDVRMPVANPFPKERALPCDSARPVPG
EYSRPTLEVSPNVCHSNIYSPKETIPEEARSDMHYSVAEGLKPAAPSARNAPYFPCDKAS
KEEERPSSEDEIALHFEPPNAPLNRKGLVSPQSPQKSDCQPNSPTESCSSKNACILQASG
SPPAKSPTDPKACNWKKYKFIVLNSLNQNAKPEGPEQAELGRLSPRAYTAPPACQPPMEP
ENLDLQSPTKLSASGEDSTIPQASRLNNIVNRSMTGSPRSSSESHSPLYMHPPKCTSCGS
QSPQHAEMCLHTAGPTFPEEMGETQSEYSDSSCENGAFFCNECDCRFSEEASLKRHTLQT
HSDKPYKCDRCQASFRYKGNLASHKTVHTGEKPYRCNICGAQFNRPANLKTHTRIHSGEK
PYKCETCGARFVQVAHLRAHVLIHTGEKPYPCEICGTRFRHLQTLKSHLRIHTGEKPYHC
EKCNLHFRHKSQLRLHLRQKHGAITNTKVQYRVSATDLPPELPKAC
Target Type
Literature-reported
Target Bioclass
Transcription factor
Subcellular location
Nucleus
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.
TTD ID
T43548
Uniprot ID
P41182
DrugMap ID
TTC9YX5
Ensemble ID
ENST00000232014.8
HGNC ID
HGNC:1001
ChEMBL ID
CHEMBL4105786

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A498 SNV: p.L490I DBIA    Probe Info 
HKGZCC SNV: p.Q152E .
HT115 SNV: p.R674Q .
IGROV1 Deletion: p.R459AfsTer131 .
KU1919 Substitution: p.A517I .
KYSE510 SNV: p.P458S .
NALM6 SNV: p.R640W DBIA    Probe Info 
NCIH358 SNV: p.A45S .
OCILY3 SNV: p.C525S; p.G559R .
RAMOS SNV: p.A587D IA-alkyne    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C339(1.32); C348(1.32)  LDD0078  [1]
IA-alkyne
 Probe Info 
N.A.  LDD0167  [2]
NAIA_5
 Probe Info 
N.A.  LDD2225  [3]
IPM
 Probe Info 
C175(0.00); C296(0.00)  LDD0147  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C339(1.32); C348(1.32)  LDD0078  [1]
 LDCM0632  CL-Sc Hep-G2 C8(1.44)  LDD2227  [3]
 LDCM0625  F8 Ramos C175(0.96)  LDD2187  [5]
 LDCM0572  Fragment10 Ramos C175(1.60)  LDD2189  [5]
 LDCM0574  Fragment12 Ramos C175(0.96)  LDD2191  [5]
 LDCM0575  Fragment13 Ramos C175(0.96)  LDD2192  [5]
 LDCM0576  Fragment14 Ramos C175(1.03)  LDD2193  [5]
 LDCM0579  Fragment20 Ramos C175(1.41)  LDD2194  [5]
 LDCM0580  Fragment21 Ramos C175(1.00)  LDD2195  [5]
 LDCM0582  Fragment23 Ramos C175(1.09)  LDD2196  [5]
 LDCM0578  Fragment27 Ramos C175(0.96)  LDD2197  [5]
 LDCM0586  Fragment28 Ramos C175(0.81)  LDD2198  [5]
 LDCM0588  Fragment30 Ramos C175(1.19)  LDD2199  [5]
 LDCM0589  Fragment31 Ramos C175(1.09)  LDD2200  [5]
 LDCM0590  Fragment32 Ramos C175(1.33)  LDD2201  [5]
 LDCM0468  Fragment33 Ramos C175(0.99)  LDD2202  [5]
 LDCM0596  Fragment38 Ramos C175(0.92)  LDD2203  [5]
 LDCM0566  Fragment4 Ramos C175(0.96)  LDD2184  [5]
 LDCM0610  Fragment52 Ramos C175(1.21)  LDD2204  [5]
 LDCM0614  Fragment56 Ramos C175(1.78)  LDD2205  [5]
 LDCM0571  Fragment9 Ramos C175(1.37)  LDD2188  [5]
 LDCM0022  KB02 Ramos C175(1.38)  LDD2182  [5]
 LDCM0023  KB03 Ramos C175(0.94)  LDD2183  [5]
 LDCM0024  KB05 COLO792 C175(3.91)  LDD3310  [6]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 10 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone deacetylase 4 (HDAC4) Histone deacetylase family P56524
Histone deacetylase 9 (HDAC9) Histone deacetylase family Q9UKV0
Mitochondrial inner membrane protease ATP23 homolog (ATP23) Peptidase M76 family Q9Y6H3
Proteasome subunit beta type-4 (PSMB4) Peptidase T1B family P28070
Protein phosphatase PTC7 homolog (PPTC7) PP2C family Q8NI37
Tribbles homolog 3 (TRIB3) CAMK Ser/Thr protein kinase family Q96RU7
E3 ubiquitin-protein ligase SIAH1 (SIAH1) SINA (Seven in absentia) family Q8IUQ4
TNF receptor-associated factor 2 (TRAF2) TNF receptor-associated factor family Q12933
Kinesin-like protein KIFC3 (KIFC3) Kinesin family Q9BVG8
F-box only protein 11 (FBXO11) . Q86XK2
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Arrestin domain-containing protein 3 (ARRDC3) Arrestin family Q96B67
Copper homeostasis protein cutC homolog (CUTC) CutC family Q9NTM9
Transcription factor
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Pre-B-cell leukemia transcription factor 4 (PBX4) TALE/PBX homeobox family Q9BYU1
B-cell lymphoma 6 protein (BCL6) . P41182
Golgin-45 (BLZF1) . Q9H2G9
Zinc finger and BTB domain-containing protein 7B (ZBTB7B) . O15156
Other
Click To Hide/Show 19 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Sperm axonemal maintenance protein CFAP97D1 (CFAP97D1) CFAP97 family B2RV13
CCR4-NOT transcription complex subunit 2 (CNOT2) CNOT2/3/5 family Q9NZN8
Golgin subfamily A member 2 (GOLGA2) GOLGA2 family Q08379
Keratin-associated protein 19-1 (KRTAP19-1) KRTAP type 19 family Q8IUB9
Keratin-associated protein 13-2 (KRTAP13-2) PMG family Q52LG2
Prefoldin subunit 5 (PFDN5) Prefoldin subunit alpha family Q99471
Sperm microtubule inner protein 6 (SPMIP6) SMRP1 family Q8NCR6
Tektin-4 (TEKT4) Tektin family Q8WW24
TLE family member 5 (TLE5) WD repeat Groucho/TLE family Q08117
WD repeat domain-containing protein 83 (WDR83) WD repeat MORG1 family Q9BRX9
Zinc finger HIT domain-containing protein 1 (ZNHIT1) ZNHIT1 family O43257
Cilia- and flagella-associated protein 161 (CFAP161) . Q6P656
Kelch-like protein 12 (KLHL12) . Q53G59
LIM and senescent cell antigen-like-containing domain protein 4 (LIMS4) . P0CW20
MYND-type zinc finger-containing chromatin reader ZMYND8 (ZMYND8) . Q9ULU4
Protein SPMIP2 (SPMIP2) . Q96LM5
Sperm-associated microtubule inner protein 4 (SPMIP4) . Q8N865
TNF receptor-associated factor 1 (TRAF1) . Q13077
TP53-binding protein 1 (TP53BP1) . Q12888

References

1 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
2 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
3 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
4 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
5 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
6 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840