IRF3
Interferon regulatory factor 3
Also known as: IRF3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q14653
- Gene
- IRF3
- Ensembl
- ENSG00000126456
- Chromosome
- 19
- Canonical length
- 427 aa
- Protein class
- Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. The protein plays an important role in the innate immune response against DNA and RNA viruses. Mutations in this gene are associated with Encephalopathy, acute, infection-induced, herpes-specific, 7. [provided by RefSeq, Sep 2020]
Canonical amino-acid sequenceUniProt
427 residues, UniProt reviewed canonical sequence.
>Q14653|IRF3
1 MGTPKPRILP WLVSQLDLGQ LEGVAWVNKS RTRFRIPWKH GLRQDAQQED FGIFQAWAEA
61 TGAYVPGRDK PDLPTWKRNF RSALNRKEGL RLAEDRSKDP HDPHKIYEFV NSGVGDFSQP
121 DTSPDTNGGG STSDTQEDIL DELLGNMVLA PLPDPGPPSL AVAPEPCPQP LRSPSLDNPT
181 PFPNLGPSEN PLKRLLVPGE EWEFEVTAFY RGRQVFQQTI SCPEGLRLVG SEVGDRTLPG
241 WPVTLPDPGM SLTDRGVMSY VRHVLSCLGG GLALWRAGQW LWAQRLGHCH TYWAVSEELL
301 PNSGHGPDGE VPKDKEGGVF DLGPFIVDLI TFTEGSGRSP RYALWFCVGE SWPQDQPWTK
361 RLVMVKVVPT CLRALVEMAR VGGASSLENT VDLHISNSHP LSLTSDQYKA YLQDLVEGMD
421 FQGPGESLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IRF3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.34
- Highest tissue expression
- 71 nTPM
Expression across tissuesHPA
Tissue
- spleen: 71 nTPM
- small intestine: 50 nTPM
- prostate: 45 nTPM
- kidney: 43 nTPM
- ovary: 43 nTPM
- thyroid gland: 42 nTPM
Single-cell type
- extravillous trophoblasts: 124 nCPM
- cytotrophoblasts: 95 nCPM
- endometrial secretory cells: 86 nCPM
- tuft cells: 81 nCPM
- paneth cells: 77 nCPM
- migrating cytotrophoblasts: 76 nCPM
Immune cell
- T-reg: 81 nTPM
- gdT-cell: 59 nTPM
- memory CD4 T-cell: 57 nTPM
- memory CD8 T-cell: 55 nTPM
- MAIT T-cell: 53 nTPM
- eosinophil: 50 nTPM
Brain region
- thalamus: 18 nTPM
- pons: 16 nTPM
- medulla oblongata: 15 nTPM
- white matter: 15 nTPM
- spinal cord: 14 nTPM
- amygdala: 14 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about IRF3.
Disease | AllUniProt
Conditions IRF3 is implicated in, by any mechanism.
- Encephalopathy, acute, infection-induced, 7, herpes-specific (IIAE7) MIM:616532
ReferencesPubMed · IEDB
Publications for IRF3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
1 publication
- Regulatory role of TRIM21 in the type-I interferon pathway in Japanese encephalitis virus-infected human microglial cells.
2014 · J Neuroinflammation · RCR 2.5 · 86 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.92
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.08
- DepMap mean gene effect
- -0.03
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antiviral innate immune response
- apoptotic process
- cellular response to exogenous dsRNA
- cellular response to virus
- cGAS/STING signaling pathway
- cytoplasmic pattern recognition receptor signaling pathway
- defense response to virus
- DNA damage response
- immune system process
- lipopolysaccharide-mediated signaling pathway
- macrophage apoptotic process
- MDA-5 signaling pathway
- mRNA transcription
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of cytokine production involved in inflammatory response
- positive regulation of interferon-alpha production
- positive regulation of interferon-beta production
- positive regulation of transcription by RNA polymerase II
- positive regulation of type I interferon production
- positive regulation of type I interferon-mediated signaling pathway
- programmed necrotic cell death
- regulation of apoptotic process
- regulation of inflammatory response
- regulation of transcription by RNA polymerase II
- toll-like receptor 4 signaling pathway
- TRIF-dependent toll-like receptor signaling pathway
- type I interferon-mediated signaling pathway
Molecular functions
- DNA binding
- DNA-binding transcription activator activity
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- identical protein binding
- promoter-specific chromatin binding
- protein domain specific binding
- protein homodimerization activity
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Interferon regulatory factor, DNA-binding domain
- SMAD/FHA domain superfamily
- SMAD-like domain superfamily
- Interferon regulatory factor-3
- Interferon regulatory factor, conserved site
- Winged helix-like DNA-binding domain superfamily
- Winged helix DNA-binding domain superfamily
- Interferon regulatory factor transcription factor
- Interferon-regulatory factor 3
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of IRF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IRF3 as an antibody target. Whether an autoantibody or antibody against IRF3 could matter depends on whether native IRF3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IRF3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label IRF3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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