| IED ID | IndEnz0002003540 |
| Enzyme Type ID | protease003540 |
| Protein Name |
Ubiquitin-like protein ISG15 Interferon-induced 15 kDa protein Interferon-induced 17 kDa protein IP17 Ubiquitin cross-reactive protein |
| Gene Name | Isg15 G1p2 Ucrp |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAWDLKVKMLGGNDFLVSVTNSMTVSELKKQIAQKIGVPAFQQRLAHQTAVLQDGLTLSSLGLGPSSTVMLVVQNCSEPLSILVRNERGHSNIYEVFLTQTVDTLKKKVSQREQVHEDQFWLSFEGRPMEDKELLGEYGLKPQCTVIKHLRLRGGGGDQCA |
| Enzyme Length | 161 |
| Uniprot Accession Number | Q64339 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: 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 down-regulating 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 (By similarity). {ECO:0000250|UniProtKB:P05161, ECO:0000269|PubMed:16254333, ECO:0000269|PubMed:17222803, ECO:0000269|PubMed:17227866, ECO:0000269|PubMed:17289916, ECO:0000269|PubMed:18057259, ECO:0000269|PubMed:22022510, ECO:0000269|PubMed:22028657, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:32726803}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (11); Chain (1); Cross-link (1); Domain (2); Helix (6); Modified residue (2); Motif (1); Propeptide (1); Region (1); Sequence conflict (2); Site (1); Turn (1) |
| Keywords | 3D-structure;Antiviral defense;Cytoplasm;Direct protein sequencing;Disulfide bond;Isopeptide bond;Reference proteome;Repeat;S-nitrosylation;Secreted;Ubl conjugation pathway |
| Interact With | Q9WTV6; K9N638; P0C6U8; P0C6X7; P0DTD1 |
| Induction | INDUCTION: By type I interferons. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P05161}. Secreted {ECO:0000250|UniProtKB:P05161}. Note=Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins. {ECO:0000250|UniProtKB:P05161}. |
| Modified Residue | MOD_RES 76; /note=S-nitrosocysteine; /evidence=ECO:0000269|PubMed:18606809; MOD_RES 144; /note=S-nitrosocysteine; /evidence=ECO:0000269|PubMed:18606809 |
| Post Translational Modification | PTM: S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins. {ECO:0000269|PubMed:18606809}.; PTM: Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases (By similarity). {ECO:0000250|UniProtKB:P05161}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (8) |
| Cross Reference PDB | 5CHF; 5CHV; 5CHW; 5JZE; 5TL7; 5TLA; 6J62; 6YVA; |
| Mapped Pubmed ID | 11217851; 11788588; 11854279; 12208842; 12426101; 12466851; 12810567; 15485925; 15568025; 16024773; 16139798; 16314524; 16615898; 16710296; 16914094; 17114181; 17381847; 18490754; 18941237; 18991290; 19004958; 20219937; 20385878; 20660068; 20810994; 21298066; 21402791; 21992229; 22057675; 22138649; 22272257; 22284419; 23012479; 23229543; 23750257; 23853600; 24137104; 24257616; 24416772; 24533902; 24648452; 24807690; 24844324; 24899198; 25031023; 25165091; 25320315; 25368022; 25505199; 25605921; 25669448; 25805508; 26210742; 26259872; 26371324; 27193971; 27412597; 27882925; 28087453; 28165509; 28264883; 28438633; 28599020; 29077752; 29100055; 29632206; 29891555; 31772204; 31924792; 32127658; 32169846; 32195343; 32202502; 32277054; 32416603; 32428392; 32553163; 32686110; 32845033; 33571167; 34380029; 34673375; |
| Motif | MOTIF 150..155; /note=LRLRGG; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 17,898 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |