dbPTM

IRF3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IRF3_HUMAN
UniProt AC	Q14653
Protein Name	Interferon regulatory factor 3
Gene Name	IRF3
Organism	Homo sapiens (Human).
Sequence Length	427
Subcellular Localization	Cytoplasm . Nucleus . Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm.
Protein Description	Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages..
Protein Sequence	MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEATGAYVPGRDKPDLPTWKRNFRSALNRKEGLRLAEDRSKDPHDPHKIYEFVNSGVGDFSQPDTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPTPFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPGWPVTLPDPGMSLTDRGVMSYVRHVLSCLGGGLALWRAGQWLWAQRLGHCHTYWAVSEELLPNSGHGPDGEVPKDKEGGVFDLGPFIVDLITFTEGSGRSPRYALWFCVGESWPQDQPWTKRLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMDFQGPGES

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MGTPKPRILP -----CCCCCCCHHH	27.17	23746807
14	Phosphorylation	RILPWLVSQLDLGQL CHHHHHHHHCCCCCC	23.90	23746807
29	Ubiquitination	EGVAWVNKSRTRFRI CCEEEECCCCCCEEC	31.53	-
32	Phosphorylation	AWVNKSRTRFRIPWK EEECCCCCCEECCCC	41.05	24732914
42 (in isoform 3)	Phosphorylation	-	4.43	29116813
70	Sumoylation	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	-
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
70	Sumoylation	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	-
70	Ubiquitination	AYVPGRDKPDLPTWK CCCCCCCCCCCCHHH	38.79	21890473
75	Phosphorylation	RDKPDLPTWKRNFRS CCCCCCCHHHHHHHH	51.41	23746807
77	Acetylation	KPDLPTWKRNFRSAL CCCCCHHHHHHHHHH	39.68	25953088
77	Ubiquitination	KPDLPTWKRNFRSAL CCCCCHHHHHHHHHH	39.68	-
87	Sumoylation	FRSALNRKEGLRLAE HHHHHHHHHCCCCHH	55.87	-
87	Sumoylation	FRSALNRKEGLRLAE HHHHHHHHHCCCCHH	55.87	-
87	Ubiquitination	FRSALNRKEGLRLAE HHHHHHHHHCCCCHH	55.87	-
97	Phosphorylation	LRLAEDRSKDPHDPH CCCHHHCCCCCCCHH	54.45	23746807
123	Phosphorylation	DFSQPDTSPDTNGGG CCCCCCCCCCCCCCC	28.32	-
135	Phosphorylation	GGGSTSDTQEDILDE CCCCCCCCHHHHHHH	33.36	-
173	Phosphorylation	PCPQPLRSPSLDNPT CCCCCCCCCCCCCCC	26.90	30266825
175	Phosphorylation	PQPLRSPSLDNPTPF CCCCCCCCCCCCCCC	49.99	23927012
180	Phosphorylation	SPSLDNPTPFPNLGP CCCCCCCCCCCCCCC	43.76	30266825
188 (in isoform 2)	Phosphorylation	-	48.48	29116813
188	Phosphorylation	PFPNLGPSENPLKRL CCCCCCCCCCCCCEE	48.48	23927012
193	Ubiquitination	GPSENPLKRLLVPGE CCCCCCCCEEECCCC	42.11	21890473
237	Phosphorylation	GSEVGDRTLPGWPVT CCEECCCCCCCCCCC	41.88	23746807
244	Phosphorylation	TLPGWPVTLPDPGMS CCCCCCCCCCCCCCC	28.61	23746807
253	Phosphorylation	PDPGMSLTDRGVMSY CCCCCCCCHHHHHHH	19.15	22210691
259	Phosphorylation	LTDRGVMSYVRHVLS CCHHHHHHHHHHHHH	20.33	22210691
292	Phosphorylation	RLGHCHTYWAVSEEL HHCCCCEEEEECHHH	2.80	-
313	Ubiquitination	GPDGEVPKDKEGGVF CCCCCCCCCCCCCCC	83.23	-
315	Ubiquitination	DGEVPKDKEGGVFDL CCCCCCCCCCCCCCC	65.47	-
339	Phosphorylation	FTEGSGRSPRYALWF EECCCCCCCEEEEEE	19.77	22210691
342	Phosphorylation	GSGRSPRYALWFCVG CCCCCCEEEEEEEEC	14.94	22210691
351	Phosphorylation	LWFCVGESWPQDQPW EEEEECCCCCCCCCC	37.82	22210691
370	Phosphorylation	VMVKVVPTCLRALVE EEEEHHHHHHHHHHH	16.74	-
385	Phosphorylation	MARVGGASSLENTVD HHHHCCCCCCCCEEE	38.44	9463386
386	Phosphorylation	ARVGGASSLENTVDL HHHCCCCCCCCEEEE	38.89	9463386
390	Phosphorylation	GASSLENTVDLHISN CCCCCCCEEEEEECC	13.16	27251275
396	Phosphorylation	NTVDLHISNSHPLSL CEEEEEECCCCCCCC	22.87	12524442
398	Phosphorylation	VDLHISNSHPLSLTS EEEEECCCCCCCCCH	21.49	23746807
402	Phosphorylation	ISNSHPLSLTSDQYK ECCCCCCCCCHHHHH	33.77	9566918
404	Phosphorylation	NSHPLSLTSDQYKAY CCCCCCCCHHHHHHH	27.21	23746807
405	Phosphorylation	SHPLSLTSDQYKAYL CCCCCCCHHHHHHHH	28.19	9566918
427	Phosphorylation	DFQGPGES------- CCCCCCCC-------	51.98	26216125

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
75	T	Phosphorylation	Kinase	STK4	Q13043	GPS
123	S	Phosphorylation	Kinase	COT	P41279	PSP
123	S	Phosphorylation	Kinase	GSK3A	P49840	PSP
123	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
135	T	Phosphorylation	Kinase	PRKDC	P78527	GPS
173	S	Phosphorylation	Kinase	MAP3K2	Q9Y2U5	GPS
173	S	Phosphorylation	Kinase	COT	P41279	PSP
173	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
173	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
173	S	Phosphorylation	Kinase	GSK3A	P49840	PSP
173	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
175	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
175	S	Phosphorylation	Kinase	COT	P41279	PSP
180	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
180	T	Phosphorylation	Kinase	GSK3A	P49840	PSP
180	T	Phosphorylation	Kinase	COT	P41279	PSP
188	S	Phosphorylation	Kinase	COT	P41279	PSP
253	T	Phosphorylation	Kinase	STK4	Q13043	GPS
292	Y	Phosphorylation	Kinase	ARG	P42684	PSP
292	Y	Phosphorylation	Kinase	ABL	P00519	PSP
385	S	Phosphorylation	Kinase	AKT3	Q9Y243	PSP
385	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
386	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
386	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
396	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
396	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
396	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
398	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
398	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
398	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
402	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
402	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
402	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
404	T	Phosphorylation	Kinase	IKBKB	O14920	GPS
404	T	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
405	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
405	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM26	Q12899	PMID:25763818
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM17	Q9Y577	PMID:18711448
-	K	Ubiquitination	E3 ubiquitin ligase	RBCK1	Q9BYM8	PMID:18711448
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM21	P19474	PMID:18641315
-	K	Ubiquitination	E3 ubiquitin ligase	RNF26	Q9BY78	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	RNF41	Q9H4P4	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM36	Q9NQ86	PMID:18711448
-	K	Ubiquitination	E3 ubiquitin ligase		B3SRS0	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of IRF3_HUMAN !!

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 IRF3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PRDX1_HUMAN	PRDX1	physical	16189514
CBP_HUMAN	CREBBP	physical	10521456
IRF7_HUMAN	IRF7	physical	11162841
IRF5_HUMAN	IRF5	physical	11303025
RO52_HUMAN	TRIM21	physical	19265157
IRF3_HUMAN	IRF3	physical	19454348
IRF3_HUMAN	IRF3	physical	19893624
CBP_HUMAN	CREBBP	physical	21903422
EP300_HUMAN	EP300	physical	21903422
RB_HUMAN	RB1	physical	21903422
RBL1_HUMAN	RBL1	physical	21903422
RBL2_HUMAN	RBL2	physical	21903422
MAVS_HUMAN	MAVS	physical	21903422
TBK1_HUMAN	TBK1	physical	21903422
CBP_HUMAN	CREBBP	physical	9488451
EP300_HUMAN	EP300	physical	9488451
IRF3_HUMAN	IRF3	physical	22114345
SOCS1_HUMAN	SOCS1	physical	21079688
TBK1_HUMAN	TBK1	physical	22388039
IRF3_HUMAN	IRF3	physical	22588174
IRF7_HUMAN	IRF7	physical	18641315
RO52_HUMAN	TRIM21	physical	18641315
PIN1_HUMAN	PIN1	physical	16699525
HERC5_HUMAN	HERC5	physical	20308324
IRF3_HUMAN	IRF3	physical	21782231
MAVS_HUMAN	MAVS	physical	22908223
TRAF3_HUMAN	TRAF3	physical	22079989
MAVS_HUMAN	MAVS	physical	16153868
IRF3_HUMAN	IRF3	physical	10082512
HS90A_HUMAN	HSP90AA1	physical	16394098
TBK1_HUMAN	TBK1	physical	16394098
CBP_HUMAN	CREBBP	physical	15107417
CBP_HUMAN	CREBBP	physical	17761676
TLR2_HUMAN	TLR2	physical	17126870
CBP_HUMAN	CREBBP	physical	17126870
IRF3_HUMAN	IRF3	physical	11940575
CBP_HUMAN	CREBBP	physical	11940575
EP300_HUMAN	EP300	physical	11940575
TOM70_HUMAN	TOMM70A	physical	20628368
HS90A_HUMAN	HSP90AA1	physical	20628368
CBP_HUMAN	CREBBP	physical	9660935
EP300_HUMAN	EP300	physical	9660935
CBP_HUMAN	CREBBP	physical	16154084
VIRF1_HHV8P	vIRF-1	physical	11314014
VIRF3_HHV8P	vIRF-3	physical	14668346
FOXO1_HUMAN	FOXO1	physical	23532851
IRF3_HUMAN	IRF3	physical	15582653
CBP_HUMAN	CREBBP	physical	15582653
MAFB_HUMAN	MAFB	physical	20581830
IRF3_HUMAN	IRF3	physical	20581830
DEAF1_HUMAN	DEAF1	physical	23846693
IRF3_HUMAN	IRF3	physical	23951545
SGTA_HUMAN	SGTA	physical	21988832
PEX19_HUMAN	PEX19	physical	21988832
IRF3_HUMAN	IRF3	physical	24622840
IRF3_HUMAN	IRF3	physical	24763515
IRF3_HUMAN	IRF3	physical	23675467
EP300_HUMAN	EP300	physical	20604809
IRF3_HUMAN	IRF3	physical	12473110
AKT1_HUMAN	AKT1	physical	21106850
MAVS_HUMAN	MAVS	physical	25636800
TBK1_HUMAN	TBK1	physical	25636800
TRAF2_HUMAN	TRAF2	physical	25636800
TRAF6_HUMAN	TRAF6	physical	25636800
MAVS_MOUSE	Mavs	physical	25636800
IRF3_HUMAN	IRF3	physical	25636800
STING_HUMAN	TMEM173	physical	25636800
TCAM1_HUMAN	TICAM1	physical	25636800
IRF3_HUMAN	IRF3	physical	26347139
TBK1_HUMAN	TBK1	physical	25803835
FAS_HUMAN	FASN	physical	25609649
SALL2_HUMAN	SALL2	physical	25609649
SMC1A_HUMAN	SMC1A	physical	25609649
WRIP1_HUMAN	WRNIP1	physical	25609649
SLMAP_HUMAN	SLMAP	physical	25609649
TBB8_HUMAN	TUBB8	physical	25609649
ASML_HUMAN	ASMTL	physical	25609649
BCAS3_HUMAN	BCAS3	physical	25609649
DCTN1_HUMAN	DCTN1	physical	25609649
ESYT2_HUMAN	ESYT2	physical	25609649
HXK2_HUMAN	HK2	physical	25609649
KIT_HUMAN	KIT	physical	25609649
AGRL2_HUMAN	LPHN2	physical	25609649
PSA5_HUMAN	PSMA5	physical	25609649
SMC2_HUMAN	SMC2	physical	25609649
SORT_HUMAN	SORT1	physical	25609649
SNG3_HUMAN	SYNGR3	physical	25609649
TEX36_HUMAN	TEX36	physical	25609649
TROP_HUMAN	TRO	physical	25609649
IRF3_HUMAN	IRF3	physical	26456228
CBP_HUMAN	CREBBP	physical	25733689
TRI26_HUMAN	TRIM26	physical	25763818
IPO5_HUMAN	IPO5	physical	26811330
IRF3_HUMAN	IRF3	physical	26407194
IRF3_HUMAN	IRF3	physical	26221961
IRF3_HUMAN	IRF3	physical	23986588
CBL_HUMAN	CBL	physical	27503123
MSRA_HUMAN	MSRA	physical	28514442
GLMN_HUMAN	GLMN	physical	28514442
MOCOS_HUMAN	MOCOS	physical	28514442
UBP19_HUMAN	USP19	physical	28514442
DOCK7_HUMAN	DOCK7	physical	28514442
CE034_HUMAN	C5orf34	physical	28514442
GRDN_HUMAN	CCDC88A	physical	28514442
ANR40_HUMAN	ANKRD40	physical	28514442
TBK1_HUMAN	TBK1	physical	28346439

Drug and Disease Associations

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.

Regulatory Network of IRF3_HUMAN

Related Literatures of Post-Translational Modification