ISG15
ISG15 (ISG15 ubiquitin like modifier, also known as IFI15, UCRP and G1P2) is a ubiquitin-like protein that plays a key role in the innate immune response to viral infection. It acts either conjugated to target proteins (ISGylation) or as a free protein, inside the cell and as a secreted cytokine. Browse Assay Genie's current range of ISG15 research reagents below, or read on for the biology behind the target.
ISG15 is a ubiquitin-like protein with a central role in antiviral innate immunity. In ISGylation, a cascade of E1, E2 and E3 enzymes catalyses the conjugation of ISG15 to a lysine residue in a target protein. Reported targets include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7 and the ESCRT-related proteins CHMP5, CHMP2A, CHMP4B and CHMP6. The effect depends on the substrate. ISGylation of the viral sensor IFIH1/MDA5 promotes its oligomerisation and triggers innate immune activation, while ISGylation of EIF2AK2/PKR activates it and ISGylation of RIGI inhibits its function in antiviral signalling. ISGylation of IRF3 inhibits its ubiquitination and degradation, and ISGylation of FLNB inhibits IFNA-induced JNK signalling.
Unconjugated ISG15 also has antiviral activity against both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. It restricts HIV-1 and Ebola virus by disrupting viral budding: it inhibits ubiquitination of HIV-1 Gag and host TSG101, and it disrupts the ubiquitin ligase activity of NEDD4 on the Ebola VP40 protein. ISGylation of influenza A virus NS1 causes loss of function of that protein. The secreted form of ISG15 can induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as an IFN-gamma-inducing cytokine important in antimycobacterial immunity. It signals through the integrin ITGAL/ITGB2 receptor, activating SRC family kinases including LYN, HCK and FGR, which leads to secretion of IFNG and IL10.
The ISG15 gene is induced by interferon-alpha and interferon-beta, and the protein is found in the cytoplasm and in secreted form. Conjugates have been found noncovalently attached to intermediate filaments. The gene was previously named interferon, alpha-inducible protein (clone IFI-15K), and the mouse ortholog is Isg15. Researchers studying ISG15 protein or the ISG15 gene often work on interferon signalling, viral restriction and cytokine biology.
ISG15 contributes to the innate response to viruses, including coronaviruses, flaviviruses, picornaviruses, influenza A, HIV-1 and Ebola virus.
ISG15 is conjugated through E1, E2 and E3 enzymes to substrates such as IFIH1/MDA5, EIF2AK2/PKR, IRF3 and RIGI, altering their activity.
Secreted ISG15 induces natural killer cell proliferation, attracts neutrophils and drives IFN-gamma production through the ITGAL/ITGB2 receptor.
Secreted ISG15 acts as an IFN-gamma-inducing cytokine that plays an essential role in antimycobacterial immunity.
ISG15 is an interferon-induced ubiquitin-like protein that supports the innate immune response to viral infection. It can be conjugated to target proteins by ISGylation, act as a free intracellular protein, or be secreted to act as a cytokine on natural killer cells and neutrophils.
ISG15 is also known as IFI15, UCRP and G1P2. The HGNC full name is ISG15 ubiquitin like modifier, the UniProt name is ubiquitin-like protein ISG15, and the gene was previously called interferon, alpha-inducible protein (clone IFI-15K).
A mouse ortholog, Isg15, is recorded for the human gene. Check the datasheet of any product for its validated reactivity before using it in a given species.
Interferon-stimulated gene products and other antiviral immune targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P05161; product specifications from Assay Genie datasheets.