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Rabbit Anti-IRF3 Recombinant Antibody (CBYY-I1681) (CBMAB-I2851-YY)


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Summary

Host Animal
Rabbit
Specificity
Human, Monkey
Clone
CBYY-I1681
Application
WB, IP, IF

Basic Information

Specificity
Human, Monkey
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

Target

Full Name
Interferon Regulatory Factor 3
Introduction
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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
Entrez Gene ID
Human3661
Monkey718970
UniProt ID
HumanQ14653
MonkeyA0A0D9S3X7
Alternative Names
Interferon Regulatory Factor 3
Function
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 (PubMed:22394562, PubMed:25636800, PubMed:27302953).
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 (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995).
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 (PubMed:16846591, PubMed:16979567, PubMed:20049431).
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 (PubMed:22394562, PubMed:25636800, PubMed:27302953).
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 (PubMed:16154084, PubMed:27302953, PubMed:33440148).
Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591).
In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812).
Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).
Biological Process
Apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to DNA damage stimulusManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to exogenous dsRNAIEA:Ensembl
Cellular response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Defense response to virusISS:UniProtKB
Immune system processManual Assertion Based On ExperimentIBA:GO_Central
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Macrophage apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
MDA-5 signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingIEA:Ensembl
Positive regulation of interferon-alpha productionISS:UniProtKB
Positive regulation of interferon-beta productionISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of type I interferon productionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of type I interferon-mediated signaling pathwayIEA:Ensembl
Programmed necrotic cell deathIEA:Ensembl
Regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of inflammatory responseIEA:Ensembl
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
TRIF-dependent toll-like receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Type I interferon signaling pathwayIEA:Ensembl
Cellular Location
Cytoplasm; Nucleus; Mitochondrion. Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect (PubMed:10805757).
When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm (PubMed:10805757).
Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection (PubMed:25609812).
Involvement in disease
Encephalopathy, acute, infection-induced, 7, herpes-specific (IIAE7):
A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.
PTM
Constitutively phosphorylated on many Ser/Thr residues (PubMed:22394562, PubMed:23478265, PubMed:23746807).
Activated following phosphorylation by TBK1 and IKBKE (PubMed:23478265, PubMed:23746807, PubMed:25636800).
Innate adapter protein MAVS, STING1 or TICAM1 are first activated by viral RNA, cytosolic DNA, and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE (PubMed:25636800).
These kinases then phosphorylate the adapter proteins on the pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800).
Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25636800).
Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation (PubMed:18711448).
Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation (PubMed:18641315).
Ubiquitinated by UBE3C, leading to its degradation (PubMed:21167755).
ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation.
Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (PubMed:30878284).
Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction (PubMed:30878284).
(Microbial infection) ISGylated. ISGylation is cleaved and removed by SARS-COV-2 nsp3 which attenuates type I interferon responses.
(Microbial infection) Phosphorylation and subsequent activation of IRF3 is inhibited by vaccinia virus protein E3.
More Infomation

Su, J., Guan, B., Chen, K., Feng, Z., Guo, K., Wang, X., ... & Chen, Q. (2023). Fucoxanthin attenuates inflammation via interferon regulatory factor 3 (IRF3) to improve sepsis. Journal of Agricultural and Food Chemistry, 71(33), 12497-12510.

Freitas, R. S., Crum, T. F., & Parvatiyar, K. (2022). SARS-CoV-2 spike antagonizes innate antiviral immunity by targeting interferon regulatory factor 3. Frontiers in Cellular and Infection Microbiology, 11, 1350.

Rashid, F., Suleman, M., Shah, A., Dzakah, E. E., Wang, H., Chen, S., & Tang, S. (2021). Mutations in SARS-CoV-2 ORF8 altered the bonding network with interferon regulatory factor 3 to evade host immune system. Frontiers in Microbiology, 12, 703145.

Glanz, A., Chakravarty, S., Varghese, M., Kottapalli, A., Fan, S., Chakravarti, R., & Chattopadhyay, S. (2021). Transcriptional and non-transcriptional activation, posttranslational modifications, and antiviral functions of interferon regulatory factor 3 and viral antagonism by the SARS-coronavirus. Viruses, 13(4), 575.

Tang, P., Virtue, S., Goie, J. Y. G., Png, C. W., Guo, J., Li, Y., ... & Zhang, Y. (2021). Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3. Cell Death & Differentiation, 28(11), 3022-3035.

Petro, T. M. (2020). IFN regulatory factor 3 in health and disease. The Journal of Immunology, 205(8), 1981-1989.

Guinn, Z. P., & Petro, T. M. (2019). Interferon regulatory factor 3 plays a role in macrophage responses to interferon-γ. Immunobiology, 224(4), 565-574.

Sanz‐Garcia, C., McMullen, M. R., Chattopadhyay, S., Roychowdhury, S., Sen, G., & Nagy, L. E. (2019). Nontranscriptional Activity of Interferon Regulatory Factor 3 Protects Mice From High‐Fat Diet‐Induced Liver Injury. Hepatology Communications, 3(12), 1626-1641.

Wong, H. H., Fung, T. S., Fang, S., Huang, M., Le, M. T., & Liu, D. X. (2018). Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology, 515, 165-175.

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For research use only. Not intended for any clinical use.

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