Descriptions

IRF3 is a key transcriptional regulator of type I interferon (IFN)-dependent immune responses and is present in an inactive cytoplasmic form. Human IRF3 (Q14653) contains a C-terminal region containing phosphorylation sites. Phosphorylation of the sites converts IRF3 into a constitutively active form. The C-terminal autoinhibitory region intramolecularly interact with N-terminal region overlapping with an atypical transactivation domain.

Autoinhibitory domains (AIDs)

Target domain

197-376 (IFN association domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

2 structures for P70671

Entry ID Method Resolution Chain Position Source
7JFM X-ray 223 A A/B 184-390 PDB
AF-P70671-F1 Predicted AlphaFoldDB

8 variants for P70671

Variant ID(s) Position Change Description Diseaes Association Provenance
rs37980697 48 M>I No Ensembl
rs246430893 94 A>V No Ensembl
rs235494303 147 I>V No Ensembl
rs260341506 152 K>T No Ensembl
rs37133231 168 Q>R No Ensembl
rs241421235 189 Q>L No Ensembl
rs227684734 215 F>Y No Ensembl
rs213981800 251 K>R No Ensembl

No associated diseases with P70671

39 regional properties for P70671

Type Name Position InterPro Accession
repeat Thrombospondin type-1 (TSP1) repeat 57 - 111 IPR000884-1
repeat Thrombospondin type-1 (TSP1) repeat 338 - 397 IPR000884-2
repeat Thrombospondin type-1 (TSP1) repeat 399 - 463 IPR000884-3
repeat Thrombospondin type-1 (TSP1) repeat 461 - 521 IPR000884-4
repeat Thrombospondin type-1 (TSP1) repeat 524 - 577 IPR000884-5
repeat Thrombospondin type-1 (TSP1) repeat 576 - 640 IPR000884-6
repeat Thrombospondin type-1 (TSP1) repeat 639 - 694 IPR000884-7
domain Pancreatic trypsin inhibitor Kunitz domain 1610 - 1663 IPR002223-1
domain Pancreatic trypsin inhibitor Kunitz domain 1668 - 1722 IPR002223-2
domain Pancreatic trypsin inhibitor Kunitz domain 1728 - 1781 IPR002223-3
domain Pancreatic trypsin inhibitor Kunitz domain 1788 - 1841 IPR002223-4
domain Pancreatic trypsin inhibitor Kunitz domain 1847 - 1900 IPR002223-5
domain Pancreatic trypsin inhibitor Kunitz domain 1920 - 1973 IPR002223-6
domain Pancreatic trypsin inhibitor Kunitz domain 1999 - 2052 IPR002223-7
domain Pancreatic trypsin inhibitor Kunitz domain 2069 - 2122 IPR002223-8
domain Pancreatic trypsin inhibitor Kunitz domain 2126 - 2179 IPR002223-9
domain Pancreatic trypsin inhibitor Kunitz domain 2192 - 2245 IPR002223-10
domain Pancreatic trypsin inhibitor Kunitz domain 2251 - 2304 IPR002223-11
domain Pancreatic trypsin inhibitor Kunitz domain 2316 - 2372 IPR002223-12
domain Immunoglobulin subtype 2 2534 - 2599 IPR003598-1
domain Immunoglobulin subtype 2 2631 - 2694 IPR003598-2
domain Immunoglobulin subtype 2 2766 - 2831 IPR003598-3
domain Immunoglobulin subtype 2528 - 2611 IPR003599-1
domain Immunoglobulin subtype 2625 - 2701 IPR003599-2
domain Immunoglobulin subtype 2760 - 2842 IPR003599-3
domain Immunoglobulin-like domain 2523 - 2607 IPR007110-1
domain Immunoglobulin-like domain 2617 - 2697 IPR007110-2
domain Immunoglobulin-like domain 2749 - 2840 IPR007110-3
domain WAP-type 'four-disulfide core' domain 2452 - 2498 IPR008197
domain ADAMTS/ADAMTS-like, Spacer 1 217 - 329 IPR010294
domain PLAC 2847 - 2886 IPR010909
domain Immunoglobulin I-set 2766 - 2840 IPR013098
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 1640 - 1658 IPR020901-1
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 1758 - 1776 IPR020901-2
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 1877 - 1895 IPR020901-3
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 2099 - 2117 IPR020901-4
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 2222 - 2240 IPR020901-5
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 2281 - 2299 IPR020901-6
conserved_site Proteinase inhibitor I2, Kunitz, conserved site 2349 - 2367 IPR020901-7

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Mitochondrion
  • Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect
  • When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm
  • Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

9 GO annotations of molecular function

Name Definition
DNA-binding transcription activator activity, RNA polymerase II-specific A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.
DNA-binding transcription factor activity, RNA polymerase II-specific A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.
identical protein binding Binding to an identical protein or proteins.
promoter-specific chromatin binding Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
protein domain specific binding Binding to a specific domain of a protein.
protein homodimerization activity Binding to an identical protein to form a homodimer.
RNA polymerase II cis-regulatory region sequence-specific DNA binding Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
sequence-specific DNA binding Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
sequence-specific double-stranded DNA binding Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding.

23 GO annotations of biological process

Name Definition
cellular response to lipopolysaccharide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to virus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
immune system process Any process involved in the development or functioning of the immune system, an organismal system for calibrated responses to potential internal or invasive threats.
lipopolysaccharide-mediated signaling pathway The series of molecular signals initiated by the binding of a lipopolysaccharide (LPS) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Lipopolysaccharides are major components of the outer membrane of Gram-negative bacteria, making them prime targets for recognition by the immune system.
positive regulation of cytokine production Any process that activates or increases the frequency, rate or extent of production of a cytokine.
positive regulation of I-kappaB kinase/NF-kappaB signaling Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling.
positive regulation of interferon-alpha production Any process that activates or increases the frequency, rate, or extent of interferon-alpha production.
positive regulation of interferon-beta production Any process that activates or increases the frequency, rate, or extent of interferon-beta production.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of transcription, DNA-templated Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of type I interferon production Any process that activates or increases the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
positive regulation of type I interferon-mediated signaling pathway Any process that increases the rate, frequency or extent of a type I interferon-mediated signaling pathway.
programmed necrotic cell death A necrotic cell death process that results from the activation of endogenous cellular processes, such as signaling involving death domain receptors or Toll-like receptors.
regulation of apoptotic process Any process that modulates the occurrence or rate of cell death by apoptotic process.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of inflammatory response Any process that modulates the frequency, rate or extent of the inflammatory response, the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents.
regulation of transcription by RNA polymerase II Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
response to bacterium Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium.
response to exogenous dsRNA Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an exogenous double-stranded RNA stimulus.
response to lipopolysaccharide Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
TRIF-dependent toll-like receptor signaling pathway The series of molecular signals initiated by a ligand binding to a toll-like receptor where the TRIF adaptor mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response.
type I interferon signaling pathway The series of molecular signals initiated by type I interferon binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q4JF28 IRF3 Interferon regulatory factor 3 Bos taurus (Bovine) SS
Q14653 IRF3 Interferon regulatory factor 3 Homo sapiens (Human) EV
Q61179 Irf9 Interferon regulatory factor 9 Mus musculus (Mouse) PR
P56477 Irf5 Interferon regulatory factor 5 Mus musculus (Mouse) SS
Q64287 Irf4 Interferon regulatory factor 4 Mus musculus (Mouse) EV
P70434 Irf7 Interferon regulatory factor 7 Mus musculus (Mouse) SS
P23611 Irf8 Interferon regulatory factor 8 Mus musculus (Mouse) PR
Q764M6 IRF3 Interferon regulatory factor 3 Sus scrofa (Pig) SS
10 20 30 40 50 60
METPKPRILP WLVSQLDLGQ LEGVAWLDES RTRFRIPWKH GLRQDAQMAD FGIFQAWAEA
70 80 90 100 110 120
SGAYTPGKDK PDVSTWKRNF RSALNRKEVL RLAADNSKDP YDPHKVYEFV TPGARDFVHL
130 140 150 160 170 180
GASPDTNGKS SLPHSQENLP KLFDGLILGP LKDEGSSDLA IVSDPSQQLP SPNVNNFLNP
190 200 210 220 230 240
APQENPLKQL LAEEQWEFEV TAFYRGRQVF QQTLFCPGGL RLVGSTADMT LPWQPVTLPD
250 260 270 280 290 300
PEGFLTDKLV KEYVGQVLKG LGNGLALWQA GQCLWAQRLG HSHAFWALGE ELLPDSGRGP
310 320 330 340 350 360
DGEVHKDKDG AVFDLRPFVA DLIAFMEGSG HSPRYTLWFC MGEMWPQDQP WVKRLVMVKV
370 380 390 400 410
VPTCLKELLE MAREGGASSL KTVDLHISNS QPISLTSDQY KAYLQDLVED MDFQATGNI