ISG15 (mature form) (human, recombinant)

Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like (Ubl) protein found only in vertebrates.^1,2 The mature form of ISG15 is composed of an N-terminal Ubl and a C-terminal Ubl with an LRLRGG conjugation sequence at the C-terminus.² It is expressed in lymphoid cells, epithelial cells, neurons, and skeletal and smooth muscle, and its expression is induced by type I interferon signaling in response to viral or bacterial infection but is also induced in response to the aging process and certain diseases.^3,1,2 ISG15 is primarily localized intracellularly conjugated to lysine residues in newly synthesized proteins via ISGylation, a process that can enhance antiviral responses.¹ It also exists in a free form that can be secreted by a variety of cells, including fibroblasts, monocytes, and lymphocytes, and binds to the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) on leukocytes to increase the secretion of IFN-γ. ISG15 can ISGylate viral proteins to prevent viral replication and inhibit the function of viral proteins, however ISGylation on host proteins can be reversed by certain viruses, including severe acute respiratory coronavirus 2 (SARS-CoV-2), leading to suppression of the host innate immune response.^1,4,5 Patients deficient in functional ISG15 due to inherited mutations in ISG15 are more resistant to viral infection, but have an increased susceptibility to mycobacterial infection, while Isg15 knockout mice are more susceptible to viral infection, indicating species-specific differences.^6,7 Cayman’s ISG15 (mature form) (human, recombinant) protein consists of 157 amino acids and has a calculated molecular weight of 17.2 kDa. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is 15 kDa.

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1. Dzimianski, J.V., Scholte, F.E.M., Bergeron, É., et al. ISG15: It’s complicated. J. Mol. Biol. 431(21), 4203-4216 (2019).

2. Zhang, D., and Zhang, D.-E. Interferon-stimulated gene 15 and the protein ISGylation system. J. Interferon Cytokine Res. 31(1), 119-130 (2011).

3. Lowe, J., McDermott, H., Loeb, K., et al. Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues. J. Pathol. 177(2), 163-169 (1995).

4. Freitas, B.T., Durie, I.A., Murray, J., et al. Characterization and noncovalent inhibition of the deubiquitinase and deISGylase activity of SARS-CoV-2 papain-like protease. ACS Infect. Dis. 6(8), 2099-2109 (2020).

5. Shin, D., Mukherjee, R., Grewe, D., et al. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature 587(7835), 657-662 (2020).

6. Speer, S.D., Li, Z., Buta, S., et al. ISG15 deficiency and increased viral resistance in humans but not mice. Nat. Commun. 7, 11496 (2016).

7. Bogunovic, D., Byun, M., Durfee, L.A., et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337(6102), 1684-1688 (2012).