dbPTM

IRF7_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IRF7_HUMAN
UniProt AC	Q92985
Protein Name	Interferon regulatory factor 7
Gene Name	IRF7
Organism	Homo sapiens (Human).
Sequence Length	503
Subcellular Localization	Nucleus. Cytoplasm. The phosphorylated and active form accumulates selectively in the nucleus.
Protein Description	Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and 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. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages..
Protein Sequence	MALAPERAAPRVLFGEWLLGEISSGCYEGLQWLDEARTCFRVPWKHFARKDLSEADARIFKAWAVARGRWPPSSRGGGPPPEAETAERAGWKTNFRCALRSTRRFVMLRDNSGDPADPHKVYALSRELCWREGPGTDQTEAEAPAAVPPPQGGPPGPFLAHTHAGLQAPGPLPAPAGDKGDLLLQAVQQSCLADHLLTASWGADPVPTKAPGEGQEGLPLTGACAGGPGLPAGELYGWAVETTPSPGPQPAALTTGEAAAPESPHQAEPYLSPSPSACTAVQEPSPGALDVTIMYKGRTVLQKVVGHPSCTFLYGPPDPAVRATDPQQVAFPSPAELPDQKQLRYTEELLRHVAPGLHLELRGPQLWARRMGKCKVYWEVGGPPGSASPSTPACLLPRNCDTPIFDFRVFFQELVEFRARQRRGSPRYTIYLGFGQDLSAGRPKEKSLVLVKLEPWLCRVHLEGTQREGVSSLDSSSLSLCLSSANSLYDDIECFLMELEQPA

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
13 (in isoform 4)	Phosphorylation	-	4.88	-
50	Ubiquitination	PWKHFARKDLSEADA CHHHHCCCCCHHHHH	60.64	-
53	Phosphorylation	HFARKDLSEADARIF HHCCCCCHHHHHHHH	40.65	21712546
61	Ubiquitination	EADARIFKAWAVARG HHHHHHHHHHHHHCC	40.42	-
74 (in isoform 4)	Ubiquitination	-	40.49	-
92	Acetylation	TAERAGWKTNFRCAL HHHHHCCCHHHHHHH	32.45	12374802
92	Ubiquitination	TAERAGWKTNFRCAL HHHHHCCCHHHHHHH	32.45	12374802
93	O-linked_Glycosylation	AERAGWKTNFRCALR HHHHCCCHHHHHHHH	32.83	30379171
105	Acetylation	ALRSTRRFVMLRDNS HHHCCCCEEEEECCC	3.23	12374802
105 (in isoform 4)	Ubiquitination	-	3.23	-
120 (in isoform 3)	Ubiquitination	-	42.18	21890473
120 (in isoform 2)	Ubiquitination	-	42.18	21890473
120 (in isoform 1)	Ubiquitination	-	42.18	21890473
120	Ubiquitination	GDPADPHKVYALSRE CCCCCHHHHHEEEHH	42.18	21890473
125	Phosphorylation	PHKVYALSRELCWRE HHHHHEEEHHHHHCC	18.61	29496907
133 (in isoform 4)	Ubiquitination	-	19.84	21890473
303	Ubiquitination	KGRTVLQKVVGHPSC CCCCHHHHHHCCCCC	34.43	-
312 (in isoform 2)	Ubiquitination	-	6.08	21890473
316 (in isoform 4)	Ubiquitination	-	19.30	-
341	Ubiquitination	PAELPDQKQLRYTEE CCCCCCHHHHHHHHH	59.69	2190698
341 (in isoform 1)	Ubiquitination	-	59.69	21890473
354 (in isoform 4)	Ubiquitination	-	6.06	21890473
375	Ubiquitination	ARRMGKCKVYWEVGG HHHHCCCEEEEEECC	41.67	-
386	Phosphorylation	EVGGPPGSASPSTPA EECCCCCCCCCCCCC	31.20	27251275
388 (in isoform 4)	Ubiquitination	-	22.53	-
388	Phosphorylation	GGPPGSASPSTPACL CCCCCCCCCCCCCEE	22.53	27251275
390	Phosphorylation	PPGSASPSTPACLLP CCCCCCCCCCCEECC	44.52	27251275
391	Phosphorylation	PGSASPSTPACLLPR CCCCCCCCCCEECCC	20.49	27251275
399 (in isoform 4)	Phosphorylation	-	26.52	27251275
404 (in isoform 4)	Phosphorylation	-	5.85	27251275
444	Sumoylation	DLSAGRPKEKSLVLV CCCCCCCCCCEEEEE	76.14	-
444	Ubiquitination	DLSAGRPKEKSLVLV CCCCCCCCCCEEEEE	76.14	-
446	Sumoylation	SAGRPKEKSLVLVKL CCCCCCCCEEEEEEE	56.04	-
446	Sumoylation	SAGRPKEKSLVLVKL CCCCCCCCEEEEEEE	56.04	-
446	Ubiquitination	SAGRPKEKSLVLVKL CCCCCCCCEEEEEEE	56.04	-
452	Ubiquitination	EKSLVLVKLEPWLCR CCEEEEEEECCCEEE	42.86	-
452	Sumoylation	EKSLVLVKLEPWLCR CCEEEEEEECCCEEE	42.86	-
465 (in isoform 4)	Ubiquitination	-	18.31	-
471	Phosphorylation	GTQREGVSSLDSSSL CCCCCCCCCCCHHHH	35.72	-
472	Phosphorylation	TQREGVSSLDSSSLS CCCCCCCCCCHHHHH	33.51	-
475	Phosphorylation	EGVSSLDSSSLSLCL CCCCCCCHHHHHHHH	27.41	-
477	Phosphorylation	VSSLDSSSLSLCLSS CCCCCHHHHHHHHHH	26.40	15367631
479	Phosphorylation	SLDSSSLSLCLSSAN CCCHHHHHHHHHHHC	20.98	15367631
483	Phosphorylation	SSLSLCLSSANSLYD HHHHHHHHHHCHHHH	26.80	-
484	Phosphorylation	SLSLCLSSANSLYDD HHHHHHHHHCHHHHH	20.65	-
487	Phosphorylation	LCLSSANSLYDDIEC HHHHHHCHHHHHHHH	28.20	-

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
471	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
471	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
472	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
472	S	Phosphorylation	Kinase	TBK1	Q9UHD2	PSP
477	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
477	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
479	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
479	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	TRAF6	Q9Y4K3	PMID:18710948
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM28	Q13263	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM21	P19474	PMID:21183682

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
477	S	Phosphorylation	15367631
In response to a viral infection, phosphorylated on Ser-477 and Ser-479 by TBK1 and IKBKE1.
479	S	Phosphorylation	15367631
In response to a viral infection, phosphorylated on Ser-477 and Ser-479 by TBK1 and IKBKE1.

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 IRF7_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IRF7_HUMAN	IRF7	physical	11162841
IRF3_HUMAN	IRF3	physical	11162841
TRAF6_HUMAN	TRAF6	physical	21183682
TNAP3_HUMAN	TNFAIP3	physical	20392859
RO52_HUMAN	TRIM21	physical	20668674
ARAF_HUMAN	ARAF	physical	21903422
CCD47_HUMAN	CCDC47	physical	21903422
IRAK1_HUMAN	IRAK1	physical	21903422
TRM2A_HUMAN	TRMT2A	physical	21903422
LTN1_HUMAN	LTN1	physical	21903422
AIP_HUMAN	AIP	physical	21903422
HACE1_HUMAN	HACE1	physical	21903422
IQEC1_HUMAN	IQSEC1	physical	21903422
P4HA1_HUMAN	P4HA1	physical	21903422
PALD_HUMAN	PALD1	physical	21903422
TLK2_HUMAN	TLK2	physical	21903422
TR61B_HUMAN	TRMT61B	physical	21903422
EP300_HUMAN	EP300	physical	12604599
CBP_HUMAN	CREBBP	physical	12604599
TIF1B_HUMAN	TRIM28	physical	21940674
IRF7_HUMAN	IRF7	physical	22588174
IRF3_HUMAN	IRF3	physical	18641315
IRAK1_HUMAN	IRAK1	physical	15767370
MAVS_HUMAN	MAVS	physical	16153868
DEAF1_HUMAN	DEAF1	physical	23846693
NMI_HUMAN	NMI	physical	23956435
TRAF6_HUMAN	TRAF6	physical	26224488

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
616345	Immunodeficiency 39 (IMD39)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of IRF7_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Acetylation of interferon regulatory factor-7 by p300/CREB-bindingprotein (CBP)-associated factor (PCAF) impairs its DNA binding."; Caillaud A., Prakash A., Smith E., Masumi A., Hovanessian A.G.,Levy D.E., Marie I.; J. Biol. Chem. 277:49417-49421(2002). Cited for: FUNCTION, ACETYLATION AT LYS-92, MUTAGENESIS OF GLY-90; LYS-92 ANDTHR-93, AND PHOSPHORYLATION.	12374802 [Abstract]
Phosphorylation
Reference	PubMed
"Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitisvirus infection and the role of viral ribonucleoprotein in thedevelopment of interferon antiviral immunity."; tenOever B.R., Sharma S., Zou W., Sun Q., Grandvaux N., Julkunen I.,Hemmi H., Yamamoto M., Akira S., Yeh W.C., Lin R., Hiscott J.; J. Virol. 78:10636-10649(2004). Cited for: PHOSPHORYLATION AT SER-477 AND SER-479 BY TBK1 AND IKKE, ANDMUTAGENESIS OF 477-SER--SER-479.	15367631 [Abstract]
Sumoylation
Reference	PubMed
"Tripartite motif-containing protein 28 is a small ubiquitin-relatedmodifier E3 ligase and negative regulator of IFN regulatory factor7."; Liang Q., Deng H., Li X., Wu X., Tang Q., Chang T.H., Peng H.,Rauscher F.J. III, Ozato K., Zhu F.; J. Immunol. 187:4754-4763(2011). Cited for: SUMOYLATION AT LYS-444 AND LYS-446 BY TRIM28.	21940674 [Abstract]

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