BCL6_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: BCL6_MOUSE
• UniProt AC: P41183
• Protein Name: B-cell lymphoma 6 protein homolog
• Gene Name: Bcl6
• Organism: Mus musculus (Mouse).
• Sequence Length: 707
• 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: MASPADSCIQFTRHASDVLLNLNRLRSRDILTDVVIVVSREQFRAHKTVLMACSGLFYSIFTDQLKCNLSVINLDPEISPEGFCILLDFMYTSRLNLREGNIMAVMTTAMYLQMEHVVDTCRKFIKASEAEMAPALKPPREEFLNSRMLMPHDIMAYRGREVVENNMPLRNTPGCESRAFAPPLYSGLSTPPASYPMYSHLPLSTFLFSDEELRDAPRMPVANPFPKERALPCDSARQVPNEYSRPAMEVSPSLCHSNIYSPKEAVPEEARSDIHYSVPEGPKPAVPSARNAPYFPCDKASKEEERPSSEDEIALHFEPPNAPLNRKGLVSPQSPQKSDCQPNSPTESCSSKNACILQASGSPPAKSPTDPKACNWKKYKFIVLNSLNQNAKPEGSEQAELGRLSPRAYPAPPACQPPMEPANLDLQSPTKLSASGEDSTIPQASRLNNLVNRSLAGSPRSSSESHSPLYMHPPKCTSCGSQSPQHTEMCLHTAGPTFPEEMGETQSEYSDSSCENGTFFCNECDCRFSEEASLKRHTLQTHSDKPYKCDRCQASFRYKGNLASHKTVHTGEKPYRCNICGAQFNRPANLKTHTRIHSGEKPYKCETCGARFVQVAHLRAHVLIHTGEKPYPCEICGTRFRHLQTLKSHLRIHTGEKPYHCEKCNLHFRHKSQLRLHLRQKHGAITNTKVQYRVSAADLPPELPKAC

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MASPADSCIQ -----CCCHHHHHHH	21.23	22324799
251	Phosphorylation	SRPAMEVSPSLCHSN CCCCCCCCHHHCCCC	8.75	29514104
261	Phosphorylation	LCHSNIYSPKEAVPE HCCCCCCCCHHHCCH	26.21	29514104
308	Phosphorylation	SKEEERPSSEDEIAL CCCCCCCCCCCCEEH	53.21	29550500
309	Phosphorylation	KEEERPSSEDEIALH CCCCCCCCCCCEEHC	52.31	25521595
331	Phosphorylation	LNRKGLVSPQSPQKS CCCCCCCCCCCCCCC	23.43	25521595
334	Phosphorylation	KGLVSPQSPQKSDCQ CCCCCCCCCCCCCCC	32.46	25521595
344	Phosphorylation	KSDCQPNSPTESCSS CCCCCCCCCCCCCCC	39.62	30352176
346	Phosphorylation	DCQPNSPTESCSSKN CCCCCCCCCCCCCCC	40.11	25521595
360	Phosphorylation	NACILQASGSPPAKS CEEEEEECCCCCCCC	27.17	26643407
362	Phosphorylation	CILQASGSPPAKSPT EEEEECCCCCCCCCC	25.80	21082442
367	Phosphorylation	SGSPPAKSPTDPKAC CCCCCCCCCCCCCCC	34.83	30352176
369	Phosphorylation	SPPAKSPTDPKACNW CCCCCCCCCCCCCCC	72.52	26643407
380	Acetylation	ACNWKKYKFIVLNSL CCCCCEEEEEEEECC	37.18	-
386	Phosphorylation	YKFIVLNSLNQNAKP EEEEEEECCCCCCCC	25.24	26643407
396	Phosphorylation	QNAKPEGSEQAELGR CCCCCCCCHHHHHHC	25.52	26824392
405	Phosphorylation	QAELGRLSPRAYPAP HHHHHCCCCCCCCCC	15.81	25521595
428	Phosphorylation	PANLDLQSPTKLSAS CCCCCCCCCCCCCCC	41.66	29514104
430	Phosphorylation	NLDLQSPTKLSASGE CCCCCCCCCCCCCCC	50.27	26643407
454	Phosphorylation	LNNLVNRSLAGSPRS HHHHHHHHHCCCCCC	19.84	29514104
458	Phosphorylation	VNRSLAGSPRSSSES HHHHHCCCCCCCCCC	16.13	27149854
461	Phosphorylation	SLAGSPRSSSESHSP HHCCCCCCCCCCCCC	41.42	26643407
462	Phosphorylation	LAGSPRSSSESHSPL HCCCCCCCCCCCCCC	39.13	26643407
463	Phosphorylation	AGSPRSSSESHSPLY CCCCCCCCCCCCCCC	44.35	26643407
465	Phosphorylation	SPRSSSESHSPLYMH CCCCCCCCCCCCCCC	31.08	26643407
467	Phosphorylation	RSSSESHSPLYMHPP CCCCCCCCCCCCCCC	26.36	24899341
470	Phosphorylation	SESHSPLYMHPPKCT CCCCCCCCCCCCCCC	9.21	29472430
570	Phosphorylation	ASHKTVHTGEKPYRC CCCCEEECCCCCEEC	42.58	19367708

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
344	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
334	S	Phosphorylation	Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-334 and Ser-344.	21183079
344	S	Phosphorylation	Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-334 and Ser-344.	-
380	K	Acetylation	Acetylated at Lys-380 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function.	23455674

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of BCL6_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PPARD_MOUSE	Ppard	physical	20211142
CDN2A_MOUSE	Cdkn2a	physical	15567177
ARF_MOUSE	Cdkn2a	physical	15567177
CDN2A_HUMAN	CDKN2A	physical	15567177
ARF_HUMAN	CDKN2A	physical	15567177
BCL6B_MOUSE	Bcl6b	physical	9632807
BCL6B_MOUSE	Bcl6b	physical	16331266
BACH2_MOUSE	Bach2	physical	16331266
BCL6_MOUSE	Bcl6	physical	16331266
TBX21_MOUSE	Tbx21	physical	22406686
OSTP_MOUSE	Spp1	physical	25436971

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.