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FLASH GENE

Symbol

IRF7

contributors: mct/ - updated : 30-01-2018

HGNC name	interferon regulatory factor 7
HGNC id	6122

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       predominantly   thymus

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage
cell lines
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	the last three C-terminal lysine sites (positions 444, 446, and 452) of IRF7 variant A are essential for activation of IRF7

conjugated

PhosphoP

mono polymer

complex

HOMOLOGY

Homologene

FAMILY

interferon regulatory transcription factor (IRF) family

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	activation leads to nuclear retention, DNA binding, and repression of transactivation ability

basic FUNCTION	essential regulator of IFNA, via the virus-activated, MYD88-independent pathway and the toll-like receptor (TLR)-activated, MYD88-dependent pathway
	IFN-stimulated genes and Epstein-Barr virus
	transcriptional activation of virus-inducible cellular genes
	involved in translational control of the innate immune response
	master regulator of type I IFN responses and has been shown to be critical for innate antiviral immunity
	plays important roles in innate immunity and immune cell differentiation
	is a novel modulator of neointima formation and VSMC proliferation
	master transcription factor that plays a pivotal role in the transcriptional activation of type I interferon genes in the inflammatory response
	IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans
	is a key regulator of type I interferon and plays essential roles in restricting virus infection and spread
	represents a novel regulator of Granulocytic- myeloid-derived suppressor cells (MDSCs)development in cancer, which may have predictive value for tumor progression

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

a component	component of VAF (virus-activated factor) which is composed of IRF7, IRF3, and the transcriptional coactivator proteins p300 and CBP
	forming a complex with MYD88
	forms a complex with TLR9 and promotes association of TRAF3 and AP3B1

INTERACTION

DNA	binding to interferon stimulated response element (ISRE) in IFN promoter and in the Q promoter of EBV nuclear antigen-1 (EBNA1)

RNA

small molecule

protein	interacting with IRF3 in a biologically active complex
	substrate for TRAF6 E3 ligase and IRF7 is ubiquitinated by TRAF6 at multiple sites
	its expression induces multiple IFNA genes
	GBP4 is a negative regulator of virus-triggered IFNI production, and it is identified as a novel protein targeting IRF7 and inhibiting its function
	IRF7 gene is a critical target of FOXO3 (FOXO3 was identified as a negative regulator of IRF7 transcription)
	PELI3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons
	NMI is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7
	IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition
	TRIM35 is a negative feedback regulator of TLR7/9-mediated type I IFN production due to its ability to suppress the stability of IRF7
	AIP (aryl hydrocarbon receptor interacting protein) is a new binding partner of IRF7
	AIP is a novel inhibitor of IRF7 and a negative regulator of innate antiviral signaling
	BCL6 specifically binds to the interferon-regulatory factor IRF7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon IFNB1 production and antiviral responses
	IRF7 directly binds to the two conserved IRF binding sites on the USP25 promoter to drive transcription of USP25, and mutation of these two sites abolished Sendai virus-induced IRF7-mediated activation of the USP25 promoter
	adaptor molecule CRADD coordinates IKBKE and IRF7 interaction to ensure efficient expression of type I interferon
	NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production
	S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein
	IRF3 and IRF7 bind to many interferon-stimulated response element (ISRE)-type sites in the virus-response elements (VREs) of IFN promoters
	TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function (PMID

cell & other

REGULATION

activated by	TRAF6
	TRAF3 (TRF3 activates IRF7 through K63-linked ubiquitination which requires RIP1 and TRAF6)

induced by	lipopolysaccharide, virus infection, and IFNA but not by IFNG
		the IFN-triggered Jak-STAT pathway

repressed by

TNFAIP3 (negatively regulates IRF7 transcriptional activity induced by TRAF3)

Other	phosphorylated and activated by IKKE or TBK1
	is targeted for degradation by binding to the RTA immediate-early nuclear transcription factor encoded by KSHV
	ubiquitination is required for phosphorylation and activation of IRF7

ASSOCIATED DISORDERS

corresponding disease(s)

IMD39

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   most lung cells from stable Chronic Obstructive Pulmonary Disease (COPD) patients show a constitutive decreased expression of IFNB1, IRF7, DDX58 and IFIH1, suggesting that this deficiency is the main cause of their acute viral exacerbations

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   may represent a promising target for vascular disease therapy

ANIMAL & CELL MODELS

Irf7-null mice are consistently more vulnerable than Myd88-null mice to viral infection, and this correlated with marked decrease in serum interferon levels, indicating the importance of the IRF7-dependent induction of systemic interferon responses for innate antiviral immunity