dbPTM

TF65_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	TF65_MOUSE
UniProt AC	Q04207
Protein Name	Transcription factor p65
Gene Name	Rela
Organism	Mus musculus (Mouse).
Sequence Length	549
Subcellular Localization	Nucleus . Cytoplasm . Colocalized with DDX1 in the nucleus upon TNF-alpha induction (By similarity). Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). Colocalizes with GFI1 in the nucleus after lipopo
Protein Description	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity). The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (By similarity)..
Protein Sequence	MDDLFPLIFPSEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGYYEADLCPDRSIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFHVPIEEQRGDYDLNAVRLCFQVTVRDPAGRPLLLTPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFNGPTEPRPPTRRIAVPTRNSTSVPKPAPQPYTFPASLSTINFDEFSPMLLPSGQISNQALALAPSSAPVLAQTMVPSSAMVPLAQPPAPAPVLTPGPPQSLSAPVPKSTQAGEGTLSEALLHLQFDADEDLGALLGNSTDPGVFTDLASVDNSEFQQLLNQGVSMSHSTAEPMLMEYPEAITRLVTGSQRPPDPAPTPLGTSGLPNGLSGDEDFSSIADMDFSALLSQISS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDDLFPLI -------CCCCCCCC	9.03	-
38	Cysteine persulfide	GMRFRYKCEGRSAGS CCCEEEEECCCCCCC	5.06	-
38	Glutathionylation	GMRFRYKCEGRSAGS CCCEEEEECCCCCCC	5.06	17468103
38	S-nitrosylation	GMRFRYKCEGRSAGS CCCEEEEECCCCCCC	5.06	22244329
38	Sulfhydration	GMRFRYKCEGRSAGS CCCEEEEECCCCCCC	5.06	22244329
42	Phosphorylation	RYKCEGRSAGSIPGE EEEECCCCCCCCCCC	48.08	30635358
45	Phosphorylation	CEGRSAGSIPGERST ECCCCCCCCCCCCCC	25.90	28973931
99	Phosphorylation	GKDCRDGYYEADLCP CCCCCCCCEECCCCC	11.47	-
109	Phosphorylation	ADLCPDRSIHSFQNL CCCCCCCCCHHHHHC	31.84	-
112	Phosphorylation	CPDRSIHSFQNLGIQ CCCCCCHHHHHCCCE	27.19	-
122	Acetylation	NLGIQCVKKRDLEQA HCCCEEEEHHCHHHH	50.12	60261
122	Malonylation	NLGIQCVKKRDLEQA HCCCEEEEHHCHHHH	50.12	26320211
123	Acetylation	LGIQCVKKRDLEQAI CCCEEEEHHCHHHHH	30.65	60267
123	Ubiquitination	LGIQCVKKRDLEQAI CCCEEEEHHCHHHHH	30.65	22790023
131	Phosphorylation	RDLEQAISQRIQTNN HCHHHHHHHHHHHCC	19.20	25338131
176	Phosphorylation	AGRPLLLTPVLSHPI CCCCEEEEECCCCCC	16.01	25521595
180	Phosphorylation	LLLTPVLSHPIFDNR EEEEECCCCCCCCCC	27.70	23984901
203	Phosphorylation	ICRVNRNSGSCLGGD EEEECCCCCCCCCCC	28.93	-
205	Phosphorylation	RVNRNSGSCLGGDEI EECCCCCCCCCCCEE	13.14	-
218	Acetylation	EIFLLCDKVQKEDIE EEEEEECCCCHHCEE	45.64	60921
221	Acetylation	LLCDKVQKEDIEVYF EEECCCCHHCEEEEE	61.41	60915
238	Phosphorylation	PGWEARGSFSQADVH CCCHHCCCCHHHHHC	19.03	25521595
240	Phosphorylation	WEARGSFSQADVHRQ CHHCCCCHHHHHCCC	26.59	28066266
254	Phosphorylation	QVAIVFRTPPYADPS CEEEEEECCCCCCCC	19.70	-
261	Phosphorylation	TPPYADPSLQAPVRV CCCCCCCCCCCCEEE	33.39	-
276	Phosphorylation	SMQLRRPSDRELSEP EEEECCCCCCCCCCC	47.70	18408078
281	Phosphorylation	RPSDRELSEPMEFQY CCCCCCCCCCCCCEE	34.60	-
306	Phosphorylation	EEKRKRTYETFKSIM HHHHHHHHHHHHHHH	19.60	25195567
310	Methylation	KRTYETFKSIMKKSP HHHHHHHHHHHHHCC	46.63	21131967
310	Acetylation	KRTYETFKSIMKKSP HHHHHHHHHHHHHCC	46.63	23806337
311	Phosphorylation	RTYETFKSIMKKSPF HHHHHHHHHHHHCCC	24.59	12881425
322	O-linked_Glycosylation	KSPFNGPTEPRPPTR HCCCCCCCCCCCCCC	61.08	32038294
335	Phosphorylation	TRRIAVPTRNSTSVP CCCEEEECCCCCCCC	35.56	29472430
338	Phosphorylation	IAVPTRNSTSVPKPA EEEECCCCCCCCCCC	20.83	23684622
339	Phosphorylation	AVPTRNSTSVPKPAP EEECCCCCCCCCCCC	36.97	29472430
340	Phosphorylation	VPTRNSTSVPKPAPQ EECCCCCCCCCCCCC	35.92	29472430
433	Phosphorylation	STQAGEGTLSEALLH CCCCCCCCHHHHHHH	23.86	-
467	Phosphorylation	GVFTDLASVDNSEFQ CHHCCCCCCCHHHHH	36.98	19270718
504	Phosphorylation	EAITRLVTGSQRPPD HHHHHHHHCCCCCCC	35.39	21737676
527	Phosphorylation	SGLPNGLSGDEDFSS CCCCCCCCCCCCHHH	45.67	-
533	Phosphorylation	LSGDEDFSSIADMDF CCCCCCHHHHHHCCH	32.91	-
534	Phosphorylation	SGDEDFSSIADMDFS CCCCCHHHHHHCCHH	23.07	20710027
545	Phosphorylation	MDFSALLSQISS--- CCHHHHHHHHCC---	26.73	-

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
276	S	Phosphorylation	Kinase	KS6A5	Q8C050	PhosphoELM
276	S	Phosphorylation	Kinase	RPS6KA5	O75582	GPS
276	S	Phosphorylation	Kinase	RPS6KA4	Q9Z2B9	Uniprot
276	S	Phosphorylation	Kinase	PRKACA	P05132	GPS
276	S	Phosphorylation	Kinase	PKACA	P17612	PSP
311	S	Phosphorylation	Kinase	KPCZ	Q02956	PhosphoELM
467	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
467	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
467	S	Phosphorylation	Kinase	IKKE	Q9R0T8	Uniprot
504	T	Phosphorylation	Kinase	CHEK1	O35280	Uniprot
527	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
527	S	Phosphorylation	Kinase	CK2	-	Uniprot
534	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
534	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
534	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
534	S	Phosphorylation	Kinase	CHUK	Q60680	GPS
534	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
534	S	Phosphorylation	Kinase	IKKA	O15111	PSP
545	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Pdlim2	Q8R1G6	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Socs1	O35716	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
38	C	S-nitrosylation	22244329
S-nitrosylation of Cys-38 inactivates the enzyme activity.
122	K	Acetylation	-
Acetylation at Lys-122 enhances DNA binding and impairs association with NFKBIA.
276	S	Phosphorylation	12881425
Phosphorylation at Ser-276 by RPS6KA4 and RPS6KA5 promotes its transactivation and transcriptional activities.
310	K	Methylation	21131967
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes.
310	K	Phosphorylation	21131967
Phosphorylation on Ser-534 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (By similarity).
310	K	Phosphorylation	21131967
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes.
310	K	Methylation	21131967
Monomethylation at Lys-310 is recognized by the ANK repeats of EHMT1 and promotes the formation of repressed chromatin at target genes, leading to down-regulation of NF-kappa-B transcription factor activity.
310	K	Methylation	21131967
Monomethylated at Lys-310 by SETD6.
310	K	Acetylation	21131967
Phosphorylation on Ser-534 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (By similarity).
310	K	Acetylation	21131967
Lys-310 is deacetylated by SIRT2 (By similarity).
310	K	Acetylation	21131967
Interaction with BRMS1 promotes deacetylation of Lys-310.
310	K	Acetylation	21131967
Acetylation at Lys-310 promotes interaction with BRD4.
310	K	Acetylation	21131967
Acetylation at Lys-310 is required for full transcriptional activity in the absence of effects on DNA binding and NFKBIA association.
311	S	Methylation	12881425
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes.
311	S	Phosphorylation	12881425
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 and promotes transcription factor activity.
311	S	Phosphorylation	12881425
Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes.
534	S	Acetylation	12881425
Phosphorylation on Ser-534 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (By similarity).
534	S	Phosphorylation	12881425
Phosphorylation on Ser-534 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (By similarity).

Disease-associated PTM Sites based on SAP

* 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 TF65_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HDAC1_MOUSE	Hdac1	physical	11931769
TF65_MOUSE	Rela	physical	20211142
SRBP1_MOUSE	Srebf1	physical	20211142
ZMY11_MOUSE	Zmynd11	physical	20211142
CXXC1_MOUSE	Cxxc1	physical	20211142
ANKR7_MOUSE	Ankrd7	physical	20211142
CERS2_MOUSE	Cers2	physical	20211142
ANR33_MOUSE	Ankrd33	physical	20211142
PIAS3_MOUSE	Pias3	physical	20211142
ZDH13_MOUSE	Zdhhc13	physical	20211142
EP300_MOUSE	Ep300	physical	20211142
EP300_MOUSE	Ep300	physical	12672795
HDAC6_MOUSE	Hdac6	physical	12372765
CITE2_MOUSE	Cited2	genetic	21098220
IKBA_MOUSE	Nfkbia	physical	21098220
SP1_MOUSE	Sp1	physical	21262356
JUN_MOUSE	Jun	physical	21262356
IKBA_MOUSE	Nfkbia	physical	20634424
IKBA_MOUSE	Nfkbia	physical	16163708
CTNB1_MOUSE	Ctnnb1	physical	17445771
NFKB2_MOUSE	Nfkb2	physical	18362156
FM1AA_MOUSE	Fem1a	physical	18270204
PPARG_MOUSE	Pparg	physical	23250430
EP300_MOUSE	Ep300	physical	23999430

Drug and Disease Associations

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

Regulatory Network of TF65_MOUSE

Related Literatures of Post-Translational Modification

Methylation
Reference	PubMed
"Lysine methylation of the NF-kappaB subunit RelA by SETD6 couplesactivity of the histone methyltransferase GLP at chromatin to tonicrepression of NF-kappaB signaling."; Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P.,Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I.,Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X.,Prinjha R.K., Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A.,Cheng X., Gozani O.; Nat. Immunol. 12:29-36(2011). Cited for: FUNCTION, SUBCELLULAR LOCATION, METHYLATION AT LYS-310,PHOSPHORYLATION AT SER-311, INTERACTION WITH EHMT1, AND MUTAGENESIS OFLYS-310.	21131967 [Abstract]
Phosphorylation
Reference	PubMed
"Lysine methylation of the NF-kappaB subunit RelA by SETD6 couplesactivity of the histone methyltransferase GLP at chromatin to tonicrepression of NF-kappaB signaling."; Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P.,Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I.,Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X.,Prinjha R.K., Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A.,Cheng X., Gozani O.; Nat. Immunol. 12:29-36(2011). Cited for: FUNCTION, SUBCELLULAR LOCATION, METHYLATION AT LYS-310,PHOSPHORYLATION AT SER-311, INTERACTION WITH EHMT1, AND MUTAGENESIS OFLYS-310.	21131967 [Abstract]
"Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaBtranscriptional activation."; Duran A., Diaz-Meco M.T., Moscat J.; EMBO J. 22:3910-3918(2003). Cited for: PHOSPHORYLATION AT SER-311.	12881425 [Abstract]
S-nitrosylation
Reference	PubMed
"Hydrogen sulfide-linked sulfhydration of NF-kappaB mediates itsantiapoptotic actions."; Sen N., Paul B.D., Gadalla M.M., Mustafa A.K., Sen T., Xu R., Kim S.,Snyder S.H.; Mol. Cell 45:13-24(2012). Cited for: FUNCTION, SULFHYDRATION AT CYS-38, S-NITROSYLATION AT CYS-38, ANDMUTAGENESIS OF CYS-38.	22244329 [Abstract]

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