Mouse Ubiquitin-like protein ISG15(ISG15) ELISA kit

Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, TRIM25, STAT5A, MAPK1/ERK2 and globin. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses. Can also isgylate: DDX58/RIG-I which inhibits its function in antiviral signaling response, IRF3 which inhibits its ubiquitination and degradation as well as EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A and B virus, sindbis virus (SV) and herpes simplex type-1 (HHV-1). Plays a significant role in the control of neonatal Chikungunya virus (CHIKV) infection by acting as a putative immunomodulator of proinflammatory cytokines. Protects mice against the consequences of Chikungunya virus infection by downregulating the pathogenic cytokine response, often denoted as the cytokine storm. Plays a role in erythroid differentiation. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL.

1. ISGylation is a ubiquitin-like modification that controls exosome release. ISGylation induction decreases microvesicular body numbers and impairs exosome secretion. Specifically, ISGylation of the MVB protein TSG101 induces its aggregation and degradation, being sufficient to impair exosome secretion. PMID: 27882925
2. Murine Isg15 does not control Usp18 accumulation and IFN-alpha/beta signaling. PMID: 27193971
3. Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor (CD11a/CD18) in natural killer cells. PMID: 29100055
4. results demonstrate that ISG15 governs the dynamic functionality of mitochondria, specifically, OXPHOS and mitophagy, broadening its physiological role as an antiviral agent. PMID: 29077752
5. Loss of ISG15 expression and type I IFN signaling have transient effects on bacterial burden during M. tuberculosis infection in mice PMID: 28087453
6. ISG15 acts as an immunomodulator in the cornea and plays a critical role in controlling fungal keratitis. PMID: 28599020
7. USP18's ISG15 specificity is mediated by a small interaction interface. PMID: 28165509
8. Posttranslational protein modification by ISG15 plays an important role in antiviral defense PMID: 25805508
9. These studies provide evidence, ISG15 is elevated following TBI in mice, preceding MLCK elevation, development of BBB disruption, and cerebral edema. PMID: 25669448
10. Kruppel-like factor 9 (KLF9) is a haploinsufficient tumor suppressor in the ApcMin/+ mouse colon by suppressing expression of ISG15, an apoptosis-inhibiting cytokine. PMID: 26210742
11. Propose that Isg15-dependent degradation of p53 represents an alternative mechanism of controlling p53 protein levels, and, thus, it is an attractive pathway for drug discovery. PMID: 24844324
12. Embryo mortality occurs in pregnant Isg15(-/-) mice, is exacerbated by environmental insults like maternal hypoxia, and might result from impaired early decidualization, vascular development, and formation of the labyrinth. PMID: 25505199
13. Enhanced resistance upon influenza B infection in USP18(C61A/C61A) mice was completely reversed in USP18(C61A/C61A) mice, which additionally lack ISG15, providing evidence that the observed reduction in viral titers is ISG15 dependent PMID: 25605921
14. Authors found that ISG15 protects mice from influenza A virus and Sendai virus induced lethality by a conjugation-dependent mechanism in both of these models. PMID: 25320315
15. study demonstrated that ISG15 had an anti-apoptotic effect on the beta cell line MIN6; conclusion is consistent with previous reports that ISG15 has a protective role PMID: 25031023
16. The ISG15 conjugation system represents a critical innate response mechanism in cardiomyocytes to fight the battle against invading pathogens, limiting inflammatory cardiomyopathy, heart failure, and death. PMID: 25165091
17. ISG15 does not appear to play a key role in IFN-beta-mediated C2C12 myoblast cell fusion PMID: 23750257
18. Interferon-stimulated gene 15 (ISG15) mitigates MNV-1 replication. PMID: 24899198
19. Protein interferon-stimulated gene 15 conjugation delays but does not overcome coronavirus proliferation in a model of fulminant hepatitis. PMID: 24648452
20. these results indicate an essential role of ISG15 in the cellular immune antiviral response PMID: 24137104
21. Isg15 regulates the expression of proteins that directly affect the HCV replication. The pro-viral effect of Isg15 in HCV replication might be mediated through these effector proteins. PMID: 24416772
22. Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation PMID: 23229543
23. vaccination against ISG15 results in significant CD8-mediated reductions in both primary and metastatic mammary tumor burden. PMID: 22057675
24. Data show that the HerC6 N-terminal RCC1-like domain (RLD) allows ISG15 conjugation. PMID: 22272257
25. mHERC6 is essential for endogenous murine ISGylation and thus represents the dominant ISG15 E3 ligase in mice. PMID: 22138649
26. These findings suggest that ISG15 plays an anti-dengue virus and West Nile virus function via protein ISGylation. PMID: 21992229
27. ISG15 is induced during late erythroid differentiation. PMID: 22022510
28. increased protein ISGylation might be an endogenous neuroprotective adaptation to minimize poststroke brain damage PMID: 21847135
29. expression of the ISG15 is elevated in A-T cells derived from various A-T patients, as well as in brain tissues derived from the ATM knockout mice and A-T patients, suggesting that ATM negatively regulates the ISG15 pathway PMID: 21298066
30. In addition to cellular ISGylation targets, recent reports implicate viral proteins as targets of ISG15 modification; these studies provide fresh insights into the antiviral mechanisms of ISG15.[Review] PMID: 20946978
31. replication of hepatitis C virus was inhibited by overexpression of ISG15 PMID: 20810994
32. Data show that contrary to earlier reports, up to 50% of the fetuses die between 7.5 and 12.5 d post coitum (dpc) in Isg15(-/-) mothers when mated to Isg15(-/-) fathers. PMID: 20660068
33. Ectopic expression of the Herc5-mediated ISGylation system could distinctly potentiate IFN-beta-induced antiviral effects against influenza A virus. PMID: 20385878
34. The authors demonstrate that influenza B virus NS1 protein potently antagonizes human but not mouse ISGylation, a property dependent on B/NS1 binding the N-terminal domain of human but not mouse ISG15. PMID: 20219937
35. UBP43 (USP18) specifically removes ISG15 from conjugated proteins PMID: 11788588
36. lipopolysaccharide activation of expression via interferon regulatory factor 3 PMID: 11854279
37. UBP43 plays a critical role in maintaining the homeostatic balance of ISG15-conjugated protein, and that regulation of cellular levels of ISG15 protein modification is essential for brain cell function. PMID: 12208842
38. Isg15 is one of few gene products identified in murine implantation sites to require presence of the conceptus and not simply differentiation of the stroma. PMID: 12810567
39. results suggest that the ubiquitin family protein ISG15/UCRP has novel functions in neutrophil-mediated immune mechanisms PMID: 12963022
40. Ubc8 is a major ISG15-conjugating enzyme responsible for protein ISGylation upon interferon stimulation PMID: 15485925
41. ISG15 is dispensable for STAT1 and interferon signaling PMID: 16024773
42. These data indicate that ISGylation targets proteins found in several fundamentally important cellular pathways and will contribute to understanding the physiologic role of interferon-induced ISG15 and ISG15 conjugation. PMID: 16139798
43. ISG15 expression protected against Sindbis virus-induced lethality and decreased Sindbis virus replication in multiple organs without inhibiting the spread of virus throughout the host. PMID: 16254333
44. The phenotype of UBP43(-/-) mice was not rescued by the absence of ISG15, as evident from unchanged mortality, neurological symptoms, and occurrence of hydrocephalus. PMID: 16314524
45. Results show that Ubp43 negatively regulates type I interferon signaling independent of its isopeptidase activity towards ISG15. PMID: 16710296
46. Virus-mediated subversion of the antiviral response by proteolysis of IRF-3 is counteracted by induction of ISG15 expression. PMID: 16914094
47. ISG15 is a novel antiviral molecule with activity against both RNA and DNA viruses provides a target for the development of therapies against important human pathogens PMID: 17227866
48. Isg15 and its conjugates are present in implantation sites during mid to late gestation in mice. PMID: 17381847
49. Leishmania braziliensis infection triggered transcription and phosphorylation of STAT molecules and IFN-stimulated gene 15 PMID: 18490754
50. nitrosylation of ISG15 enhances target protein ISGylation PMID: 18606809

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Cytoplasm. Secreted.

KEGG: mmu:100038882

STRING: 10090.ENSMUSP00000082548

UniGene: Mm.451527