Target Information

Target General Information

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Target ID

T38017 (Former ID: TTDR01134)

Target Name

Interferon regulatory factor 3 (IRF3)

Synonyms

IRF-3

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Gene Name

IRF3

Target Type

Literature-reported target

[1]

Function

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. 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.

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UniProt ID

IRF3_HUMAN

Sequence

MGTPKPRILPWLVSQLDLGQLEGVAWVNKSRTRFRIPWKHGLRQDAQQEDFGIFQAWAEA
TGAYVPGRDKPDLPTWKRNFRSALNRKEGLRLAEDRSKDPHDPHKIYEFVNSGVGDFSQP
DTSPDTNGGGSTSDTQEDILDELLGNMVLAPLPDPGPPSLAVAPEPCPQPLRSPSLDNPT
PFPNLGPSENPLKRLLVPGEEWEFEVTAFYRGRQVFQQTISCPEGLRLVGSEVGDRTLPG
WPVTLPDPGMSLTDRGVMSYVRHVLSCLGGGLALWRAGQWLWAQRLGHCHTYWAVSEELL
PNSGHGPDGEVPKDKEGGVFDLGPFIVDLITFTEGSGRSPRYALWFCVGESWPQDQPWTK
RLVMVKVVPTCLRALVEMARVGGASSLENTVDLHISNSHPLSLTSDQYKAYLQDLVEGMD
FQGPGES

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3D Structure

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AlphaFold

HIT2.0 ID

T63FF5

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Toll-like receptor signaling pathway	hsa04620	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
NOD-like receptor signaling pathway	hsa04621	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
RIG-I-like receptor signaling pathway	hsa04622	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Cytosolic DNA-sensing pathway	hsa04623	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	40	Degree centrality	4.30E-03	Betweenness centrality	1.87E-03
Closeness centrality	2.49E-01	Radiality	1.43E+01	Clustering coefficient	1.91E-01
Neighborhood connectivity	3.65E+01	Topological coefficient	5.89E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 11 KEGG Pathways	+
1	Toll-like receptor signaling pathway
2	RIG-I-like receptor signaling pathway
3	Cytosolic DNA-sensing pathway
4	Pertussis
5	Hepatitis C
6	Hepatitis B
7	Measles
8	Influenza A
9	Herpes simplex infection
10	Epstein-Barr virus infection
11	Viral carcinogenesis
Panther Pathway	[+] 1 Panther Pathways	+
1	Toll receptor signaling pathway
Reactome	[+] 9 Reactome Pathways	+
1	ISG15 antiviral mechanism
2	LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
3	Interferon gamma signaling
4	Interferon alpha/beta signaling
5	TRAF3-dependent IRF activation pathway
6	TRAF6 mediated IRF7 activation
7	Negative regulators of RIG-I/MDA5 signaling
8	Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
9	Factors involved in megakaryocyte development and platelet production
WikiPathways	[+] 8 WikiPathways	+
1	Toll-like receptor signaling pathway
2	Cytosolic sensors of pathogen-associated DNA
3	MyD88-independent cascade
4	ISG15 antiviral mechanism
5	Apoptosis
6	RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
7	Factors involved in megakaryocyte development and platelet production
8	Regulation of toll-like receptor signaling pathway

References

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REF 1

Inhibition of lipopolysaccharide-induced interferon regulatory factor 3 activation and protection from septic shock by hydroxystilbenes. Shock. 2004 May;21(5):470-5.

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