IRF5
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Interferon regulatory factor 5 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''IRF5''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular functions.


Function

IRF5 is a member of the
interferon regulatory factor Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a s ...
(IRF) family, a group of
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
DNA-binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...
containing
tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...
(W) repeats. Alternative splice variants encoding different isoforms exist. The regulatory and repression regions of the IRF family are mainly located in the
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
of the IRF. A 2020 study showed that an adaptor protein named TASL play an important regulatory role in IRF5 activation by being phosphorylated at the pLxIS motif, drawing a similar analogy to the
IRF3 Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. Function IRF3 is a member of the interferon regulatory transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. IR ...
activation pathway through the adaptor proteins MAVS,
STING Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a regulator protein that in humans is encoded by the STING1 gene. STING plays an important role in innate immunity. STING induces typ ...
and
TRIF TIR domain containing adaptor molecule 1 (TICAM1; formerly known as TIR-domain-containing adapter-inducing interferon-β or TRIF) is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of t ...
.


Clinical significance

IRF5 acts as a molecular switch that controls whether
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s will promote or inhibit inflammation. Blocking the production of IRF5 in macrophages may help treat a wide range of autoimmune diseases, and that boosting IRF5 levels might help treat people whose immune systems are weak, compromised, or damaged. IRF5 seems to work "either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on."


Signaling

The IRF family regulates the gene expression for the
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
(IFN) response to viral infections. IRF5 is a direct transducer to interferon signaling and is activated via phosphorylation. The IRF family can also initiate the JAK/STAT signaling pathway by binding to transmembrane receptors that activate JAK. IRFs, IFNs, and the JAK/STAT signaling pathway work together to fight viral infections in mammals through specific signals.


See also

*
Interferon regulatory factors Interferon regulatory factors (IRF) are proteins which regulate Transcription (genetics), transcription of interferons (see regulation of gene expression). Interferon regulatory factors contain a conserved sequence, conserved N-terminal region of ...


References


Further reading

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External links

* * {{JAK-STAT signaling pathway Transcription factors