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FLASH GENE
Symbol USP18 contributors: mct/npt - updated : 31-01-2016
HGNC name ubiquitin specific peptidase 18
HGNC id 12616
Location 22q11.21      Physical location : 18.632.757 - 18.660.160
Synonym name
  • ubiquitin processing protease 43 Kda
  • interferon stimulated gene
  • ubiquitin specific protease 18
  • weakly similar to T05H10.1 [C.elegans]
  • 43 kDa ISG15-specific protease
    • Synonym symbol(s) UBP43, ISG43
    EC.number 3.1.2.15
    DNA
    TYPE functioning gene
    STRUCTURE 27.41 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure IFNB response element and an AU-rich element in the promoter
    MAPPING cloned Y linked N status provisional
    Map cen - DGCR6 - USP18 - DGCR2 - TSSK2 - DGCR14 - GSCL - SLC25A1 - CLTCL1 - HIRA - MRPL40 - UFD1L - CDC45L - CLDN5 - GP1BB GP1BB - TBX1 - COMT - ZNF74 - qter
    Authors Schwer (00)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2037 43 372 - 2011 22170061
    - - - - - - 2011 22170061
  • N-terminal truncated isoform
  • shows different subcellular distribution compared with the full-length protein and enhanced deISGylation activity in the nucleus
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Digestiveliver   highly
    Respiratoryrespiratory tractlarynx  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage hematopoiesis
    cell lines differentiated human melanoma cells
    fluid/secretion
    at STAGE
    physiological period fetal
    Text spleen
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • short consensus sequences surrunding Cys (Cys box) and histidine (His box)
  • two other conserved domains commun to deubiquitin enzymes c
  • a critical hydrophobic patch in USP18 interacts with a hydrophobic region unique to ISG15, thus providing evidence that USP18's ISG15 specificity is mediated by a small interaction interface
    • HOMOLOGY
    interspecies ortholog to murine Ubp43
    intraspecies paralog to ubiquitin specific protein proteases UBR
    Homologene
    FAMILY
  • deubiquitinating protease family
  • peptidase C19 family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • deubiquitin enzyme, hydrolyzing isopeptide bonds between UB and folded protein domains such as additional UB moieties or target proteins
  • regulating BCR-ABL leukemogenesis via the type 1 interferon receptor signaling
  • G1P2 deconjugating protease having a role in innate immunity against viral infection
  • type I IFN-induced protein that deconjugates the ubiquitin-like modifier ISG15 from target proteins, was found to limit apoptotic susceptibility to IFNA or bortezomib
  • may significantly limit operation of the extrinsic apoptotic pathway triggered by type I IFN and drugs
  • IFN-inducible member of the ubiquitin-specific protease family
  • novel role in modulating conventional CD11b(+) dendritic cells development via its inhibitory effect on type I IFN signaling
  • plays a role in the negative regulation of interferon-alpha/beta signaling
  • removes ISG15 from conjugated proteins
  • key regulator of IFN signaling in beta cells, underlining the importance of this pathway in beta cell inflammation and death
  • roles of USP18 and USP20 in mediating virus-triggered signaling
    • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with G1P2 (to maintain a critical cellular balance of G1P2-conjugated proteins in both healthy and stressed organism)
  • its overexpression elevated EGFR levels in a manner requiring the catalytic cysteine of USP18
  • potent regulator of EGFR protein expression
  • direct relationship was found between USP18 and CCND1 (but not cyclin E) expression
  • covalent linkage of ISG15 interferes with viral infection and USP18 is the major protease which specifically removes ISG15 from target proteins
  • USP18 is a transcriptional target of WT1, suggesting that increased expression of USP18 following WT1 loss contributes to Wilms tumorigenesis
  • IRS4 functioned as a novel USP18-binding protein
    • cell & other
    REGULATION
    activated by upregulated in normal tumor cells when treated with IFN beta, via the JAK/STAT pathway
    induced by INF1, genotoxic stress and viral infection
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    increases the resistance to oncogenic transformation by BCR-ABL
    tumoral     --over  
    increased in the malignant versus normal lung
    constitutional       loss of function
    induces inflammation by increasing the STAT signaling and exacerbates IFN-induced beta cell apoptosis by the mitochondrial pathway of cell death
    constitutional     --low  
    promotes up-regulation of MIR7-1, which in turn inhibits EGFR expression and the tumorigenic activity of cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    novel candidate drug target for acute promyelocytic leukemia treatment
    cancer  
    antineoplastic target
    cancer  
    pharmacological inhibition of UBP43 may be of benefit in cancers and others diseases in which interferon is currently prescribed
    immunologyinfectious 
    therapeutic potential of modulating USP18 levels in treating viral infection, especially for viruses sensitive to IFN signaling
    ANIMAL & CELL MODELS
  • deletion of murine Usp18 causes an increase in free and conjugated Isg15 at the feto-maternal interface and results in fetal death
  • bone marrow cells in Ubp43-deficient mice exhibited hypersensitivity to interferon-alpha/beta-mediated apoptosis