| IED ID | IndEnz0002010092 |
| Enzyme Type ID | protease010092 |
| Protein Name |
Ubl carboxyl-terminal hydrolase 18 EC 3.4.19.- 43 kDa ISG15-specific protease hUBP43 ISG15-specific-processing protease Ubl thioesterase 18 |
| Gene Name | USP18 ISG43 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSKAFGLLRQICQSILAESSQSPADLEEKKEEDSNMKREQPRERPRAWDYPHGLVGLHNIGQTCCLNSLIQVFVMNVDFTRILKRITVPRGADEQRRSVPFQMLLLLEKMQDSRQKAVRPLELAYCLQKCNVPLFVQHDAAQLYLKLWNLIKDQITDVHLVERLQALYTIRVKDSLICVDCAMESSRNSSMLTLPLSLFDVDSKPLKTLEDALHCFFQPRELSSKSKCFCENCGKKTRGKQVLKLTHLPQTLTIHLMRFSIRNSQTRKICHSLYFPQSLDFSQILPMKRESCDAEEQSGGQYELFAVIAHVGMADSGHYCVYIRNAVDGKWFCFNDSNICLVSWEDIQCTYGNPNYHWQETAYLLVYMKMEC |
| Enzyme Length | 372 |
| Uniprot Accession Number | Q9UMW8 |
| Absorption | |
| Active Site | ACT_SITE 64; /note="Nucleophile"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093"; ACT_SITE 318; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.19.- |
| Enzyme Function | FUNCTION: Involved in the negative regulation of the inflammatory response triggered by type I interferon (PubMed:28165510, PubMed:27325888). Upon recruitment by STAT2 to the type I IFN receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I IFN signaling pathway (PubMed:28165510). Also regulates protein ISGylation. Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms (PubMed:11788588). {ECO:0000269|PubMed:11788588, ECO:0000269|PubMed:27325888, ECO:0000269|PubMed:28165510}.; FUNCTION: [Isoform 2]: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (PubMed:22170061). {ECO:0000269|PubMed:22170061}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Chain (1); Compositional bias (1); Domain (1); Natural variant (2); Region (5); Sequence conflict (1) |
| Keywords | Alternative initiation;Cytoplasm;Hydrolase;Nucleus;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | P42858; P48551; P05161; Q3LFD5 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:22170061}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:22170061}. Cytoplasm {ECO:0000269|PubMed:22170061}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 14743216; 15342634; 16189514; 16710296; 17374743; 19551150; 19615732; 20068173; 20935222; 21516116; 21592959; 22100648; 22677194; 22683641; 22731491; 22752428; 23152055; 23291318; 23700969; 23825189; 24705354; 24955730; 25036637; 25416956; 26008745; 26046984; 26240016; 27009955; 27227879; 27434537; 27605457; 27980214; 28369997; 28630501; 28709980; 28718215; 28881486; 29749454; 30068654; 30126853; 30858391; 31074081; 31455647; 31658294; 31886294; 32248821; 32527992; 33214684; 33461172; 33533212; 34001679; 34016972; 34743935; |
| Motif | |
| Gene Encoded By | |
| Mass | 43,011 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |