Gene Report

Basic Information

Approved Symbol	IRF3
Approved Name	interferon regulatory factor 3
Location	19q13.3-q13.4
Position	chr19:50168888-50169132 (-)
External Links	Entrez Gene: 3661 Ensembl: ENSG00000126456 UCSC: uc002pow.3 HGNC ID: 6118
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between IRF3 and MDD (count: 0)

Positive relationships between IRF3 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
IRF3		anxiety disorder(anxiety disorder)	symptoms	Redei, 2015	Patients and nomal controls	effect-size=-0.86	On the basis of the hypothesis that chronic stress markers, ...... On the basis of the hypothesis that chronic stress markers, such as those developed from our CRS model, might also track anxiety-like states, we evaluated the possibility of differential expression of the transcript panel between those who were diagnosed with MDD with or without a comorbid anxiety disorder. This intragroup analysis revealed medium-to-large effect-size differences in 18 of the 26 candidate biomarkers.thus, the nonoverlapping candidates FAM46A, NAGA, TLR7, ZNF291/SCAPER, AHSP DGKA, GCLM,GGA3, IRF3, KIAA1539,and SLC4A1 are specific to MDDcomorbidwith anxiety.Theoverlapping transcripts CD59,IGSF4A/CADM1,AMFR,CAT,CDR2, CMAS,and PSME1 might represent transcriptomic alterations common to both major depression and anxiety disorders ormay represent a consistent alteration in EOMDD patients with depression regardless of comorbidities. More...

Positive relationship network of IRF3 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between IRF3 and MDD (count: 0)

Negative relationships between IRF3 and other components at different levels (count: 0)

IRF3 related SNPs in MK4MDD (count: 0)

IRF3 related proteins in MK4MDD (count: 0)

IRF3 related GO terms (count: 40)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006915	apoptotic process	biological process	TAS[20049431]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0016032	viral process	biological process	IEA
GO:0005515	protein binding	molecular function	IPI[15841462\|16362036\|17599067\|18309294\|18583960\|18711448\|19153231\|20308324\|20581830\|21903422\|21988832\|22908223\|26347139]
GO:0032480	negative regulation of type I interferon production	biological process	TAS
GO:0097300	programmed necrotic cell death	biological process	IEA
GO:0039530	MDA-5 signaling pathway	biological process	TAS[16979567]
GO:0043330	response to exogenous dsRNA	biological process	IEA
GO:0035666	TRIF-dependent toll-like receptor signaling pathway	biological process	TAS
GO:0003677	DNA binding	molecular function	NAS[12062447]
GO:0005654	nucleoplasm	cellular component	TAS
GO:0060337	type I interferon signaling pathway	biological process	TAS
GO:0034142	toll-like receptor 4 signaling pathway	biological process	TAS
GO:0045087	innate immune response	biological process	TAS
GO:0006974	cellular response to DNA damage stimulus	biological process	TAS[16979567]
GO:0002224	toll-like receptor signaling pathway	biological process	TAS
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling	biological process	IEA
GO:0005634	nucleus	cellular component	IDA[17079289\|18818105]
GO:0071888	macrophage apoptotic process	biological process	TAS[16846591]
GO:0005737	cytoplasm	cellular component	IDA[17079289\|18818105]
GO:0001078	transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding	molecular function	IEA
GO:0002756	MyD88-independent toll-like receptor signaling pathway	biological process	TAS
GO:0071359	cellular response to dsRNA	biological process	IEA
GO:0045351	type I interferon biosynthetic process	biological process	IEA
GO:0032728	positive regulation of interferon-beta production	biological process	ISS; TAS[16979567]
GO:0032481	positive regulation of type I interferon production	biological process	TAS
GO:0032727	positive regulation of interferon-alpha production	biological process	ISS
GO:0006366	transcription from RNA polymerase II promoter	biological process	TAS[8524823]
GO:0060333	interferon-gamma-mediated signaling pathway	biological process	TAS
GO:0019221	cytokine-mediated signaling pathway	biological process	TAS
GO:0034138	toll-like receptor 3 signaling pathway	biological process	TAS
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	molecular function	IEA
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IEA
GO:0051607	defense response to virus	biological process	ISS
GO:0031663	lipopolysaccharide-mediated signaling pathway	biological process	IEA
GO:0060340	positive regulation of type I interferon-mediated signaling pathway	biological process	IEA
GO:0042803	protein homodimerization activity	molecular function	IPI[12062447]
GO:0042802	identical protein binding	molecular function	IPI[15841462\|16301520\|19454348\|20403326\|20581830\|21102435\|21782231\|22000020\|25609649]
GO:0005829	cytosol	cellular component	TAS
GO:0003712	transcription cofactor activity	molecular function	TAS[8524823]
GO:0050715	positive regulation of cytokine secretion	biological process	IEA

IRF3 related KEGG pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04620	toll like_receptor_signaling_pathway	Toll-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK. More...
hsa04623	cytosolic dna_sensing_pathway	Cytosolic DNA-sensing pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell. More...
hsa04622	rig i_like_receptor_signaling_pathway	RIG-I-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular viral replication is recognized by a family of cytosolic RNA helicases termed RIG-I-like receptors (RLRs). The RLR proteins include RIG-I, MDA5, and LGP2 and are expressed in both immune and nonimmune cells. Upon recognition of viral nucleic acids, RLRs recruit specific intracellular adaptor proteins to initiate signaling pathways that lead to the synthesis of type I interferon and other inflammatory cytokines, which are important for eliminating viruses. More...

IRF3 related BioCarta pathways (count: 0)

IRF3 related Reactome pathways (count: 6)

ID	Name	Description
Gene mapped Reactome pathways
REACT_6890	activated tlr4_signalling	The first known downstream component of TLR4 signalling is t...... The first known downstream component of TLR4 signalling is the adaptor MyD88. An MyD88-independent pathway involving the adaptor MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been established for TLR4 signalling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adaptors into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by autophosphorylation, which in turn results in the interaction of IRAK with TNF-receptor-associated factor 6 (TRAF6). This leads ultimately to activation of the IB kinase (IKK) complex, with degradation of the inhibitor IB and activation of NF-B, resulting in the production of pro-inflammatory cytokines. More...
REACT_6802	innate immunity_signaling	Innate immunity encompases the nonspecific part of immunity ...... Innate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup More...
REACT_6783	toll like_receptor_3_cascade	Toll-like receptor 3 (TLR3) as was shown for mammals is expr...... Toll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and inflammatory responses of the innate immunity in combating viral infections. Mammalian TLR3 recognizes dsRNA, and that triggers the receptor to induce the activation of NF-kappaB and the production of type I interferons (IFNs). dsRNA-stimulated phosphorylation of two specific TLR3 tyrosine residues (Tyr759 and Tyr858) is essential for initiating TLR3 signaling pathways. More...
REACT_6966	toll receptor_cascades	In human, ten members of the Toll-like receptor (TLR) family...... In human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) domain in their cytoplasmic region and an Ig-like domain in the extracellular region, where each is enriched with a varying number of leucine-rich repeats (LRRs). Each TLR can recognize specific microbial pathogen components. The binding pathogens component of the TLRs initializes signaling pathways that lead to induction of Interferon alpha/beta. There are three main signaling pathways: the first is a MyD88-dependent pathway that is common to all TLRs, except TLR3; the second is a TRAM-dependent pathway that is peculiar to TLR3 and TLR4 and is mediated by TRIF and RIP1; and the third is a TRAF6-mediated pathway peculiar to TLR3. More...
REACT_6900	signaling in_immune_system	Humans are exposed to millions of potential pathogens daily,...... Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system. More...
REACT_6894	toll like_receptor_4_cascade	Toll-like Receptor 4 is a Microbe Associated Molecular Patte...... Toll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria, many of which are human or plant pathogens. It is a component of the bacterial cell wall, and a potent activator of the innate immune response in humans, causing reactions including fever, headache, nausea, diarrhoea, changes in leukocyte and platelet counts, disseminated intravascular coagulation, multiorgan failure, shock and death. All these reactions are induced by cytokines and other endogenous mediators which are produced after interaction of the LPS with the humoral and cellular targets of the host. In macrophages, lipid A (a form of LPS) activation of TLR4 triggers the biosynthesis of diverse mediators of inflammation, such as TNF-alpha and IL1-beta, and activates the production of costimulatory molecules required for the adaptive immune response. In mononuclear and endothelial cells, lipid A also stimulates tissue factor production. These events are desirable for clearing local infections, but when these various mediators and clotting factors are overproduced, they can damage small blood vessels and precipitate shock accompanied by disseminated intravascular coagulation and multiple organ failure. More...

IRF3 related interactors from protein-protein interaction data in HPRD (count: 18)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
IRF3	CREBBP	Yes	in vitro;in vivo	10521456 , 12473110
IRF3	SYT1	No	in vitro	16143103
IRF3	IRF5	No	in vitro;in vivo	11303025 , 12138184
IRF3	IRF3	Yes	in vitro	12473110
IRF3	TICAM1	No	in vivo;yeast 2-hybrid	14739303
IRF3	SMURF2	No	in vivo	15761153
IRF3	IKBKE	Yes	in vitro;in vivo	12692549 , 15695821
IRF3	IRF7	No	in vitro	11162841
IRF3	MAVS	No	in vitro;in vivo	16153868
IRF3	TICAM2	No	in vivo	14517278
IRF3	PPIB	No	in vitro	15764595
IRF3	RELA	No	in vivo	14557267
IRF3	PRDX1	No	yeast 2-hybrid	16189514
IRF3	TBK1	No	in vitro;in vivo	12692549 , 15695821
IRF3	SERPINB2	Yes	in vitro;in vivo;yeast 2-hybrid	12883638
IRF3	GRIP1	No	in vitro;yeast 2-hybrid	16362036
IRF3	EP300	Yes	in vitro	9488451
IRF3	PIAS4	No	in vivo	15251447

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways