InnateDB Innate Immunity Genes

Aside from annotating innate immunity interactions and pathways, the InnateDB curation team has also established a project to annotate genes that have a role in the innate immune response. This has been initiated in response to the fact that Gene Ontology annotation of the innate immune response is quite limited in the numbers of genes which have been identified and in response to the fact that many users have been eager to have a defined list of innate immune genes. For innate immune gene annotation, curators employ a new tool in the InnateDB curation system to associate relevant genes with publications which provide evidence for that gene having a role in innate immunity. Along with the link to the relevant publication(s), the curators provide a one-line summary of the role similar to Entrez GeneRIFs. Such genes are also automatically associated with the Gene Ontology term "innate immune response" in InnateDB, which provides a more comprehensive list of these genes for use in the InnateDB Gene Ontology over-representation analysis tool. To date, 1666 genes have been annotated to some extent (as this is an on-going process). It should be noted that it is not the intention of InnateDB to comprehensively annotate all the roles of a given gene, but rather to provide a brief indication if a gene has a role in innate immunity. You can download all InnateDB curated genes with their annotations as Excel sheet.

This list provides details of the 2281 genes which have been annotated by either InnateDB or Gene Ontology as having a role in the innate immune response and is updated weekly.

Review the latest annotations: Download View all
Gene name Annotation Added
IKBKB (Homo sapiens) PubMed 18692471: IKBKB regulates late-phase allergic reactions promoted by the release of pro-inflammatory cytokines in an NF-kappaB-dependent manner.
PubMed 20627395: Phosphorylated IKBKB is conjugated with a monoubiquitin by the E3 ubiquitin ligase TRIM21 leading to down-regulatioin of IKBKB-induced NF-kappaB signalling. The TRIM21-mediated monoubiquitination is involved in the translocation of active IKBKB to autophagosomes.
PubMed 21138416: IKBKB and other IKK kinases regulate each other by an intricate network involving phosphorylation of their catalytic and regulatory (NEMO, TANK) subunits to balance their activities during innate immunity.
PubMed 24323043: GNB2L1 (RACK1) negatively regulates NFκB activation by interacting with CHUK and IKBKB. The interaction interferes with the recruitment of the IKK complex to TRAF2 .
PubMed 26620909: The reversible ubiquitin editing of NLRC5 determines NLRC5?? IKBKB interaction dynamics and plays a crucial role in precisely regulating NFκB signalling
2016-10-28
NLRC5 (Homo sapiens) PubMed 19414032: NLRC5 is nn NLR (nucleotide-binding domain and leucine-rich repeat containing family receptors) that is part of the family of pattern recognition receptors (PRRs) and is involved in immunity against intracellular pathogens.
PubMed 20061403: NLRC5 represents a molecular switch of IFN-gamma activation sequence/IFN-specific response element signalling pathways contributing to antiviral defence mechanisms.
PubMed 20434986: NLRC5 is a negative regulator that blocks two central components of the NF-kappaB and type I interferon signalling pathways and has an important role in homeostatic control of innate immunity.
PubMed 21148033: NLRC5 is dispensable for cytokine induction in virus and bacterial infections under physiologic conditions. (Demonstrated in murine model)
PubMed 26620909: The reversible ubiquitin editing of NLRC5 determines NLRC5?? IKBKB interaction dynamics and plays a crucial role in precisely regulating NFκB signalling
2016-10-28
TLR2 (Homo sapiens) PubMed 20505832: TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and early after respiratory infection TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.
PubMed 20927103: TLR2 functions as a sensor of oxidation-associated molecular patterns, providing a key link connecting inflammation, oxidative stress, innate immunity and angiogenesis.
PubMed 21439957: TLR1 :: TLR2 dimeric pairs recognize malarial glycosylphosphatidylinositols (GPI) to initiates intracellular signalling and the production of pro-inflammatory cytokines.
PubMed 21454596: TLR2 recognizes Thermus aquaticus extracellular polysacchride, YT-1, and induces the production of cytokines TNF and IL6 in peritoneal macrophages. (Demonstrated in murine model)
PubMed 21482737: TLR2::TLR6 synergistically interacts with TLR9 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
PubMed 21512004: TLR2 is activated by gut commensal microbe, Bacteroides fragilis, to establish host-microbial symbiosis by promoting immunological tolerance. (Demonstrated in murine model)
PubMed 21566133: TLR2 and TNFSF11 signalling pathways are modulated by Porphromonas gingivalis to alter the differentiation states of osteoclasts resulting in bacteria-mediated bone loss. (Demonstrated in murine model)
PubMed 21602496: TLR2 is expressed by Muller cells, principal glia of retina, and is responsible for generating robust bactericidal activity against Staphylococcus aureus and contributing to retinal innate defence.
PubMed 21698237: TLR2 is required for rapid inflammasome activation in response to infection by cytosolic bacterial pathogens such as Francisella novicida. (Demonstrated in murine model)
PubMed 21862586: TLR2-driven integration of inducible nitric oxide synthase (iNOS), Wnt-beta-Catenin and NOTCH1 signalling contributes to its capacity to regulate a battery of genes associated with T regulatory cell lineage commitment and towards modulation of defined set of effector functions in macrophages. (Demonstrated in murine model)
PubMed 21873606: TLR2 directly recognizes glycogen, resulting in the activation of immunocytes such as macrophages to enhance the production of nitric oxide and inflammatory cytokines.
PubMed 22096480: TLR2 and TLR4 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr2/4 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
PubMed 22102818: TLR2 signalling promotes protective vaccine-enhancing Th17 cell responses when cells are stimulated with early secreted antigenic target protein 6 (ESAT-6) expressed by the virulent Mycobacterium tuberculosis strain H37Rv but not by tuberculosis vaccine Bacillus Calmette-Guérin (BCG). (Demonstrated in mice)
PubMed 22174456: TLR2 recognizes Mycobacterium tuberculosis H37Rv cell surface lipoprotein MPT83, which induces the production of TNF, IL6, and IL12B cytokines by macrophages and upregulates macrophage function. (Demonstrated in mouse)
PubMed 22216191: Mycobacterium abscessus glycopeptidolipid (GPL) prevents TLR2-mediate induction of IL8 and DEFB4A in respiratory epithelial cells.
PubMed 25353353: Interaction of filamentous hemagglutinin (FHA) with TLR2 induces an innate immune response against Bordetella pertussis and the TLR2-binding domain of FHA may contribute to immunoprotection against pertussis infection.
PubMed 25456159: Cutaneous bacteria can negatively regulate skin-driven immune responses by inducing Gr1(+)CD11b(+) myeloid-derived suppressor cells via TLR2-6 activation.
PubMed 25531754: Soluble TLR2 (sTLR2) generated by metalloproteinase activation inhibits TLR2-induced cytokine production in THP-1 cell line.
PubMed 25977263: TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
PubMed 25955717: Human Cytomegalovirus (HCMV) miR-UL112-3p efficiently targets TLR2 during HCMV infection, resulting in the inhibition of TLR2-mediated NFκB signalling.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
2016-10-28
DDX58 (Homo sapiens) PubMed 15208624: DDX58 (RIG-I) is a cytoplasmic RNA helicase that functions as an intracellular sensor of dsRNA leading to the induction of Interferon (IFN) production independently of TLR signalling.
PubMed 18948594: DDX58 (RIG-I) first and second caspase recruitment domains (CARDs) have distinct roles in TRIM25-mediated RIG-I ubiquitination, which leads to initiation of an antiviral signalling cascade.
PubMed 19074283: DDX58 serves as a critical link between TLR3 and type-II-IFN signalling pathways in innate antiviral immune responses.
PubMed 19683681: DDX58 plays an essential role in Toll-like receptor (TLR)-stimulated phagocytosis, demonstrating that DDX58 plays a role not only in antiviral responses but in antibacterial responses as well.
PubMed 18523264: DDX58 plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
PubMed 19915568: DDX58 is a sensor able to activate the inflammasome in response to certain RNA viruses by binding to the adaptor PYCARD to trigger the caspase-1 (CASP1)-dependent inflammasome activation and IL-1-beta production.
PubMed 20403326: DDX58 binds specifically to K63-polyubiquitin chains through its tandem caspase recruitment domains (CARDs) that act as a ubiquitin sensor in a manner that depends on RNA and ATP, demonstrate that un-anchored K63-polyubiquitin chains are signalling molecules in antiviral innate immunity.
PubMed 20406818: DDX58 (RIG-I) phosphorylation on serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction.
PubMed 20511549: DDX58 innate immune response to viral infection of human cells is modified by a functional polymorphism in the RIG-I caspase recruitment domain (CARD).
PubMed 19936053: DDX58 (RIG-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response. (Demonstrated in murine model)
PubMed 21690088: DDX58 and NOD2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. DDX58 negatively regulates ligand-induced NFkB signalling mediated by NOD2, and conversely, NOD2 negatively regulates type I interferon induction by DDX58.
PubMed 21695051: DDX58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus to suppress viral replication. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of DDX58.
PubMed 22072774: DDX58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling. (Demonstrated in mice)
PubMed 22912779: Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)
PubMed 23744645: DDX58 (RIG-I) stimulation with a synthetic ligand inhibits HIV replication in macrophages.
PubMed 23950712: RNF135 is essential for the association of DDX58 (RIG-I) and TRIM25, resulting in the activation of RIG-I signalling.
PubMed 24448099: ISG15 does not directly alter human rhinovirus replication but modulates immune signalling via the viral sensor protein DDX58 to impact production of CXCL10, which has been linked to innate immunity to viruses.
PubMed 24448099: Human rhinovirus infection of epithelial cells induces the expression and secretion of ISG15, which modulates immune responses via effects on DDX58, and by regulating CXCL10 production.
PubMed 24550253: The antisense L region of encephalomyocarditis virus associates with DDX58 and is a key determinant of IFIH1 stimulation of infected cells.
PubMed 25002588: IFI16 transcriptionally regulates type I interferons and DDX58 (RIG-I) and controls the interferon response to both DNA and RNA viruses.
PubMed 25520509: Paramyxoviruses trigger the DNA-damage response, a pathway required for RPS6KA5 activation of phospho Ser 276 RELA formation to trigger the IRF7-DDX58 amplification loop necessary for mucosal interferon production.
PubMed 25557055: DDX58 dually functions as an hepatitis B virus sensor activating innate signalling and as a direct antiviral factor by counteracting the viral polymerase in hepatocytes.
PubMed 26074083: DDX58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but IFIH1 is a significant contributor to the cellular defense against IAV.
PubMed 25880109: Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
PubMed 27210312: Hepatitis B virus-induced MIR146A attenuates cell-intrinsic anti-viral innate immunity through targeting DDX58 and IFIT3.
PubMed 26645583: MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
PubMed 26608320: A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
2016-10-28
PRKRA (Homo sapiens) PubMed 25784705: The G3BP1-CAPRIN1-PRKRA complex represents a new mode of PRKRA activation and links stress responses with innate immune activation through PRKRA without a requirement for foreign double-stranded RNA pattern recognition.
PubMed 26608320: A defective interfering RNA isolated from the Hu-191 vaccine strain of measles virus is sensed by PRKRA and DDX58 to initiate an innate antiviral response.
2016-10-28
TLR4 (Homo sapiens) PubMed 18326860: TLR4 is activated by LPS and this recognition activates the Src family kinases, Src, Fyn and Yes, which in turn contribute to tyrosine phosphorylation of Zonula adherens proteins to open the endothelial paracellular pathway.
PubMed 15852007: TLR4 binding to microbial ligands can be inhibited by CD180 and its helper molecule, LY86, via direct interactions with the TLR4 signalling complex.
PubMed 10196138: TLR4 is involved in lipopolysaccharide (LPS) signaling and serves as a cell-surface co-receptor for CD14, leading to LPS-mediated NF-kappaB activation and subsequent cellular events.
PubMed 20037584: TLR4-TLR6-Cd36 activation is a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation.
PubMed 20133493: TLR4 dimerize and enable rapid signal transduction against LPS stimulation on membrane-associated CD14-expressing cells.
PubMed 20360853: TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.
PubMed 20826541: TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways. TLR4 activation by LPS induces C2C12 myotube atrophy via up-regulating autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx and MuRF1.
PubMed 21442393: TLR4 transfection of eukaryotic host cells using bacterial vectors, or bactofection, was shown to reduce E. coli colonization in the kidney and the bladder in an animal model of urinary tract infection. (Demonstrated in murine model)
PubMed 21464300: TLR4 is involved in the transmission of ER stress from tumour cells to macrophages, promoting a pro-inflammatory program in the tumour microenvironment, thus facilitating tumour progression. (Demonstrated in murine model)
PubMed 21518783: TLR4 deficient murine macrophages results in the complete abrogation of TNF-alpha production during Leishmania panamensis infection. The endosomal TLR4 plays a crucial role in the activation of host macrophages and controlling the early stages of parasitic infection. (Demonstrated in murine model)
PubMed 21615666: Epithelial TLR4 activation facilitates the transcytosis of non-cytolytic uropathogenic E. coli across intact collecting duct cell layers to invade the renal interstitium in experimental urinary tract infections.
PubMed 21712422: TLR4:LY96 functions as intracellular LPS sensor and triggers a unique set of LPS responses upon recognition of phagocytosed bacteria in macrophages. (Demonstrated in murine model)
PubMed 21730052: TLR4 on dendritic cell surfaces binds to HSPA14 and induces a robust Th1 response via the MAPK and NFkB signalling pathways. (Demonstrated in mouse)
PubMed 21738466: TLR4 recognizes Clostridium difficile surface layer proteins and induces the maturation of dendritic cells to activate the innate and adaptive immune response. (Demonstrated in mouse)
PubMed 21775438: TLR4 and HSPD1 mediate myocardial ischemia-activated innate immune signalling, which plays an important role in mediating apoptosis and inflammation during ischemia/reperfusion (I/R). (Demonstrated in murine model)
PubMed 22096480: TLR4 and TLR2 are crucial for in vivo recognition of Chlamydia pneumoniae. Tlr4/2 double-deficient mice were unable to control pneumonia caused by C. pneumoniae. (Demonstrated in mice)
PubMed 22354030: TLR4 translocates to membrane lipid rafts in a ceramide-dependent manner in Helicobacter pylori infected gastric epithelial cells.
PubMed 22396536: TLR4 is involved in cell-cell contact signalling between activated apoptotic lymphocytes and dendritic cells (DC) during the maturation of DCs.
PubMed 22433865: Synthetic triacylated lipid A-molecules have the potent ability to selectively antagonize TLR4 and inhibit anti-bacterial immunity.
PubMed 22593572: The poxviral protein A46 directly inhibits TLR4 signalling by disrupting receptor complex formation.
PubMed 22962435: A human TLR4 polymorphism (D299G/T399I) impairs TLR4::LY96 dimerization and results in a dampened host response to bacterial lipids.
PubMed 22951730: TLR4 is an important regulator of wound inflammation and is essential for early skin wound healing. (Demonstrated in mice)
PubMed 24265315: TIR domain-contaning protein from Brucella melitensis, TcpB, disrupts the receptor-adaptor interaction between TLR4 and TIRAP.
PubMed 25371197: ECSIT binds to MAP3K7 and TRAF6 to form a complex that plays a pivotal role in activating TLR4-mediated NF-kB signalling.
PubMed 25505274: The TLR4/S100A8 axis is important in the activation of monocytes.
PubMed 26082489: Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
2016-10-28
NLRP3 (Homo sapiens) PubMed 25978411: Influenza A virus non-structural protein 1, NS1, physically interacts with endogenous NLRP3 downregulating NLRP3 inflammasome activation as well as NF-kB, leading to a reduction in the levels of inflammatory cytokines.
PubMed 25816776: RNA cleavage products, catalyzed by RNASEL, bind to DHX33 to facilitate the formation of a complex with MAVS and NLRP3 during viral infection.
PubMed 26610398: H. pylori infection induces the expression and activation of components of NLRP3 inflammasomes in neutrophils and this activation is independent of a functional type IV secretion system, TLR2 and TLR4.
2016-10-28
C2 (Homo sapiens) PubMed 25381436: Staphylococcus aureus extracellular adherence protein (Eap) binds to C4B to inhibit binding of both full-length C2 and its C2b fragment, disrupting the formation of the C3 proconvertase (C4b2) and significantly diminishing the extent of S. aureus opsonophagocytosis and killing by neutrophils.
PubMed 26608922: Complement interfering protein (CIP) of group B Streptococcus (GBS) shows high affinity toward C4B and inhibits its interaction with C2, presumably preventing the formation of the C4BC2A convertase and GBS phagocytic killing in the absence of anti-GBS antibodies.
2016-10-28
Ikbkb (Mus musculus) PubMed 21138416: Ikbkb and other IKK kinases regulate each other by an intricate network involving phosphorylation of their catalytic and regulatory (NEMO, TANK) subunits to balance their activities during innate immunity.
PubMed 26620909: The reversible ubiquitin editing of Nlrc5 determines Nlrc5?? Ikbkb interaction dynamics and plays a crucial role in precisely regulating NFκB signalling
2016-10-28
Card9 (Mus musculus) PubMed 20351059: Card9 is critical for full activation of innate immunity by converging signals downstream of multiple pattern recognition receptors (PRRs) and plays a pivotal role in autonomous innate host defense against tuberculosis.
PubMed 24379290: Card9 is largely dispensable for the innate immune response to oropharyngeal candidiasis whereas it is vital for the adaptive Th17 response.
PubMed 26627732: Card9-mediated activation of the innate immune system exacerbates influenza pneumonia. Card9 deficiency improves mortality with reduced inflammatory cytokine/chemokines.
2016-10-28
Nlrc5 (Mus musculus) PubMed 26620909: The reversible ubiquitin editing of Nlrc5 determines Nlrc5?? Ikbkb interaction dynamics and plays a crucial role in precisely regulating NFκB signalling
2016-10-28
C4B (Homo sapiens) PubMed 25381436: Staphylococcus aureus extracellular adherence protein (Eap) binds to C4B to inhibit binding of both full-length C2 and its C2b fragment, disrupting the formation of the C3 proconvertase (C4b2) and significantly diminishing the extent of S. aureus opsonophagocytosis and killing by neutrophils.
PubMed 26608922: Complement interfering protein (CIP) of group B Streptococcus (GBS) shows high affinity toward C4B and inhibits its interaction with C2, presumably preventing the formation of the C4BC2A convertase and GBS phagocytic killing in the absence of anti-GBS antibodies.
2016-10-28
IL22 (Homo sapiens) PubMed 18978771: IL22 plays a role in mucosal immunity where it helps constrain inflammation and protect mucosal sites.
PubMed 20870448: IL22 is a member of the IL-10 cytokine family that is produced by special immune cell populations and ts primary effects on target cells include its role in innate immune defence against infections, in tumourigenesis, and in inflammatory diseases.
PubMed 21469124: IL22 increases the TNF-alpha-dependent induction and secretion of several immune-modulatory molecules such as initial complement factors, antimicrobial peptides and chemokines in primary keratinocytes. IL22-mediated induction of innate immunity is crucial for the maintenance of epidermal integrity during infection with Candida albicans.
PubMed 21874025: IL22 is produced by lymphoid tissue-inducer cells where it regulates the maintenance of colonic lymphoid structures during Citrobacter rodentium infection, a mechanism that bridges the lymphotoxin pathway to mucosal epithelial defense mechanisms. (Demonstrated in mice)
PubMed 22921121: IL22 protects intestinal stem cells from inflammatory tissue damage and regulates sensitivity to graft versus host disease.
PubMed 24412612: Stat3 mediates protection against intestinal infection by inducing innate lymphoid cell derived-Il22. (Demonstrated in mice)
PubMed 25476703: IL22 protects against and IL22RA2 aggravates liver fibrosis and cirrhosis in chronic liver infections.
PubMed 25474109: IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
PubMed 25510212: In alveolar epithelium, IL22 upregulates DEFB4A gene expression via STAT3.
PubMed 26644377: IL22 induced at an early stage of L. monocytogenes infection enhances innate immunity against L. monocytogenes in the liver by stimulating hepatocytes to produce an antimicrobial molecule, PLA2G2A
2016-10-27
TMEM173 (Homo sapiens) PubMed 18724357: TMEM173 (STING) is an endoplasmic reticulum (ER) receptor that facilitates interferon (IFN) induction by binding to DDX58 (RIG-I) and to subunits of TRAP complex that facilitates translocation of proteins into the ER following translation.
PubMed 18818105: TMEM173 is a critical mediator of virus-triggered type I IFN signalling and a critical mediator of virus-triggered IRF3 activation.
PubMed 19776740: TMEM173 is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.
PubMed 19285439: TMEM173 is an adaptor protein that links virus-sensing receptors to IRF3 activation. RNF5 negatively regulates this virus-triggered signaling by targeting TMEM173 for ubiquitination and degradation at the mitochondria.
PubMed 19926846: TMEM173 is required for double stranded DNA-triggered innate immune responses where, upon sensing dsDNA, TMEM173 moves from the endoplasmic reticulum (ER) to the Golgi apparatus and finally reaches the cytoplasmic punctate structures to assemble with TANK-binding kinase 1 (TBK1).
PubMed 21820332: TMEM173 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. (Demonstrated in mouse)
PubMed 22000020: TMEM173 activates STAT6 during viral infection to induce genes responsible for immune cell homing. (Demonstrated in mice)
PubMed 22761576: TMEM173 is cleaved by dengue viral protease to suppress IRF3 activation and subvert antiviral immunity.
PubMed 23055924: Dengue viral NS2B3 protease complex selectively targets TMEM173 (STING) for degradation to inhibit type I IFN production in human dendritic cells.
PubMed 23542348: TMEM173 (STING) is targeted by hepatitis C viral protease to disrupt interferon signalling.
PubMed 24131791: Cyclic-di-GMP-induced levels of IFI16 suppress the expression of TMEM173 (STING).
PubMed 24449861: In herpes simplex virus 1 (HSV-1) infected cells, the stability and function of IFI16 and TMEM173 are dependent on cell derivation and the functional integrity of HSV-1 proteins ICP0 and US3 protein kinase.
PubMed 24185615: After viral infection, ELF4 binds to TMEM173 (STING) and induces type I interferon. ELF4 is critical for host antiviral defense.
PubMed 24449861: The end result of the interplay between TMEM173 (STING), IFI16, and herpes simplex virus 1 (HSV-1) is determined by the genotype of the infected cells and the functional integrity of HSV-1 proteins infected cell protein 0 (ICP0) and US3 protein kinase.
PubMed 25401470: Familial TMEM173 mutation is associated with inflammatory lupus-like manifestations.
PubMed 25425575: Cytosolic RNA:DNA hybrids are sensed by the MB21D1-TMEM173 (cGAS-STING) pathway of the innate immune system.
PubMed 25505063: Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
PubMed 25526307: Upon cytoplasmic DNA stimulation, the endoplasmic reticulum protein AMFR is recruited to and interacts with TMEM173 in an INSIG1-dependent manner.
PubMed 25792739: Stimulation of TMEM173-dependent IRF3 activation by ultraviolet radiation is due to apoptotic signalling-dependent disruption of ULK1, a pro-autophagic protein that negatively regulates TMEM173.
PubMed 26646986: 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (G10) requires STING to trigger IRF3/IFN-associated transcription in human fibroblasts and subsequently blocking replication of Chikungunya virus, Venezuelan Encephalitis virus, and Sindbis virus.
2016-10-27
IRF3 (Homo sapiens) PubMed 9463386: IRF3 is a transcription factor that activates type-1 interferon (IFN) and IFN responsive genes.
PubMed 11991981: IRF3 is directly activated after virus infection and functions as a key activator of the intermediate/early alpha/beta interferon (IFN) genes as well as the RANTES chemokine gene.
PubMed 18818105: IRF3 transcription factor induces type I interferons (IFNs) and elicits innate antiviral response. TMEM173 (MITA) is a critical mediator of virus-triggered IRF3 activation and IFN expression.
PubMed 9566918: IRF3 phosphorylation is virus-inducible and results in IRF3 alteration of protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of interferon (IFN)- and IFN-responsive genes.
PubMed 21768204: IRF3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells.
PubMed 21820332: IRF3 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Irf3/Irf7 are resistant to otherwise lethal cerebral malaria. (Demonstrated in mouse)
PubMed 22170100: IRF3 suppresses neuroinflammation through regulation of immunomodulatory MIR155 microRNA expression in astrocytes.
PubMed 22593165: HIV accessory protein Vpu targets IRF3 to endolysosome for proteolytic degradation to avoid antiviral immune responses.
PubMed 23994473: During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
PubMed 25352594: Vpu, an accessory protein encoded by HIV-1, contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis.
PubMed 25505063: Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
PubMed 25792739: Stimulation of TMEM173-dependent IRF3 activation by ultraviolet radiation is due to apoptotic signalling-dependent disruption of ULK1, a pro-autophagic protein that negatively regulates TMEM173.
PubMed 26046437: PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with MB21D1 to initiate an IRF3-dependent innate response
PubMed 26646986: 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (G10) requires STING to trigger IRF3/IFN-associated transcription in human fibroblasts and subsequently blocking replication of Chikungunya virus, Venezuelan Encephalitis virus, and Sindbis virus.
2016-10-27
PLA2G2A (Homo sapiens) PubMed 26644377: IL22 induced at an early stage of L. monocytogenes infection enhances innate immunity against L. monocytogenes in the liver by stimulating hepatocytes to produce an antimicrobial molecule, PLA2G2A
2016-10-27
MIR485 (Homo sapiens) PubMed 26645583: MIR485 exhibits bispecificity, targeting DDX58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
2016-10-27
Ddx58 (Mus musculus) PubMed 19936053: Ddx58 (Rig-I) is responsible for the cytosolic recognition of Legionella pneumophila RNA and the subsequent induction of type I IFN response.
PubMed 21690088: Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
PubMed 21695051: Ddx58, through the TRAIL pathway, initiates apoptosis in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of Ddx58. (Demonstrated in human)
PubMed 22072774: Ddx58 (RIG-I) ubiquitination is inhibited by arterivirus and nairovirus deubiquitinating enzymes (DUBs), resulting in the inhibition of RIG-I-like receptor (RLR)-mediated innate immune signalling.
PubMed 22912779: Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.
PubMed 23064150: DDX58 (RIG-I) detects cytosolic Listeria monocytogenes infections by sensing secreted bacterial nucleic acids.
PubMed 23553835: Ddx58 (RIG-I) is a positive regulator of NF-kB signalling via binding to Nfkb1 mRNA.
PubMed 23966395: Ddx58 and Ifih1 are essential pattern recognition receptors for protection against West Nile virus infection in vivo.
PubMed 24692634: Ddx58 preferentially binds to coding RNA from S. Typhimurium during infection leading to the expression of IFN beta andthis immunostimulatory activity depends on 5? triphosphorylation of RNA.
PubMed 26074083: Ddx58 is the primary pattern recognition receptor (PRR) for influenza A virus (IAV), but Ifih1 is a significant contributor to the cellular defense against IAV.
PubMed 26146945: Ddx58 acts in parallel with Zbp1 in an RNA polymerase III-dependent manner to initiate glial responses to herpes simplex virus-1.
PubMed 26645583: Mir485 exhibits bispecificity, targeting Ddx58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
2016-10-27
Mir485 (Mus musculus) PubMed 26645583: Mir485 exhibits bispecificity, targeting Ddx58 in cells with a low abundance of H5N1 virus and viral PB1 in cells with increased amounts of the H5N1 virus.
2016-10-27
NFKBIA (Homo sapiens) PubMed 9891086: NFKBIA is a common component of the heterogeneous IKK complex that mediates an essential step of the NF-kappaB signal transduction cascade by acting as an inhibitor of NF-kappaB.
PubMed 12429743: Tyrosine phosphorylation of NFKBIA is c-Src-dependent, leading to the subsequent activation of NF-kappaB.
PubMed 16931600: Nuclear transport of the NFKBIA : RELA complex, required for the appropriate regulation of NF-kappaB signalling, is facilitated by 14-3-3 proteins.
PubMed 18503636: NFKBIA ubiquitination and degradation is inhibited by ChlaDub1, a protein of Chlamydia trachomatis, suppressing NF-kappaB activation as a result.
PubMed 21454695: NFKBIA degradation occurs through the TNF-stimulated formation of autophagosomes in epithelial cells, which results in the prolonged activation of NFKB activity.
PubMed 23487427: Polymorphisms in the NFKBIA promoter are associated with pediatric lung diseases, including childhood asthma, bronchiolitis and bronchopulmonary dysplasia.
PubMed 26642243: Haploinsufficiency of A20 (HA20) is caused by high-penetrance loss-of-function germline mutations in TNFAIP3 with increased degradation of NFKBIA, nuclear translocation of RELA, increased expression of NFκB mediated proinflammatory cytokines, and defective deubiquitinating activity.
2016-10-26