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ISG15 Gene

protein-coding   GIFtS: 67
GCID: GC01P000938

ISG15 Ubiquitin-Like Modifier

(Previous names: interferon, alpha-inducible protein (clone IFI-15K))
(Previous symbol: G1P2)
  See ISG15-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
ISG15 Ubiquitin-Like Modifier1 2     IFI152 5
G1P21 2 3 5     Interferon-Induced 17-KDa/15-KDa Protein2
Interferon, Alpha-Inducible Protein (Clone IFI-15K)1 2     Interferon-Stimulated Protein, 15 KDa2
Ubiquitin Cross-Reactive Protein2 3     Ubiquitin-Like Protein ISG152
IP172 3     Interferon-Induced 15 KDa Protein3
UCRP2 3     Interferon-Induced 17 KDa Protein3
hUCRP2 3     

External Ids:    HGNC: 40531   Entrez Gene: 96362   Ensembl: ENSG000001876087   OMIM: 1475715   UniProtKB: P051613   

Export aliases for ISG15 gene to outside databases

Previous GC identifers: GC01P000478 GC01P000220


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ISG15 Gene:
The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins
upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded
protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate
filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this
protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes
secreted. (provided by RefSeq, Dec 2012)

GeneCards Summary for ISG15 Gene:
ISG15 (ISG15 ubiquitin-like modifier) is a protein-coding gene. Diseases associated with ISG15 include mendelian susceptibility to mycobacterial diseases due to complete isg15 deficiency, and japanese encephalitis. GO annotations related to this gene include protein tag.

UniProtKB/Swiss-Prot: ISG15_HUMAN, P05161
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 IFIT1, MX1/MxA,
PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its
activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its
cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates
their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to
interact with the upstream activators of the JNK cascade therby inhibiting IFNA-induced JNK signaling. Exhibits
antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts
HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101
and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits
Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability
to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and
the inhibition of virus replication. 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

Gene Wiki entry for ISG15 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000001.10  NC_018912.2  NT_032977.10  
Regulatory elements:
   Regulatory transcription factor binding sites in the ISG15 gene promoter:
         CREB   p53   deltaCREB   MyoD   STAT3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidISG15 promoter sequence
   Search Chromatin IP Primers for ISG15

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ISG15


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1p36.33   Ensembl cytogenetic band:  1p36.33   HGNC cytogenetic band: 1p36.33

ISG15 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ISG15 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P000938:  view genomic region     (about GC identifiers)

Start:
948,803 bp from pter      End:
949,920 bp from pter
Size:
1,118 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ISG15_HUMAN, P05161 (See protein sequence)
Recommended Name: Ubiquitin-like protein ISG15 precursor  
Size: 165 amino acids; 17888 Da
Subunit: Homodimer; disulfide-linked. Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme)
and UBE2E2 (E2 enzyme) (Probable). Interaction with influenza B NS1 protein inhibits its conjugation. Interacts
with NEDD4
Selected PDB 3D structures from and Proteopedia for ISG15 (see all 7):
1Z2M (3D)        2HJ8 (3D)        3PHX (3D)        3PSE (3D)        3R66 (3D)        3RT3 (3D)    
Secondary accessions: Q5SVA4 Q7Z2G2 Q96GF0

Explore the universe of human proteins at neXtProt for ISG15: NX_P05161

Explore proteomics data for ISG15 at MOPED

Post-translational modifications: 

  • S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of
    monomeric ISG15 for its conjugation to cellular proteins1
  • 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 proteases1
  • Ubiquitination2 at Lys35, Lys77
  • Modification sites at PhosphoSitePlus

  • See ISG15 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005092.1  
    ENSEMBL proteins: 
     ENSP00000368699  
    Reactome Protein details: P05161

    ISG15 Human Recombinant Protein Products:

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    Novus Biologicals ISG15 Proteins
    Novus Biologicals ISG15 Lysates
    Sino Biological Recombinant Protein for ISG15
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for ISG15
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for ISG15 

    ISG15 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ISG15
    R&D Systems Antibodies for ISG15 (ISG15/UCRP)
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    LSBio Antibodies in human, mouse, rat for ISG15

    ISG15 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for ISG15 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    2 InterPro protein domains:
     IPR000626 Ubiquitin_dom
     IPR019956 Ubiquitin

    Graphical View of Domain Structure for InterPro Entry P05161

    ProtoNet protein and cluster: P05161

    1 Blocks protein domain: IPB000626 Ubiquitin domain

    UniProtKB/Swiss-Prot: ISG15_HUMAN, P05161
    Domain: Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to
    cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is
    necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1
    domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein
    (PubMed:18356159)
    Similarity: Contains 2 ubiquitin-like domains


    Find genes that share domains with ISG15           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ISG15_HUMAN, P05161
    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 IFIT1, MX1/MxA,
    PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its
    activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its
    cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates
    their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to
    interact with the upstream activators of the JNK cascade therby inhibiting IFNA-induced JNK signaling. Exhibits
    antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts
    HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101
    and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits
    Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability
    to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and
    the inhibition of virus replication. 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
    Induction: Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including
    certain genotoxic stresses

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI16872604
    GO:0031386protein tag IEA--
         
    Find genes that share ontologies with ISG15           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for ISG15:
     Decreased influenza A H1N1 (A/  Decreased influenza A H1N1 (A/  Decreased influenza A/WSN/33 r  Increased cell death HMECs cel 

         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Isg15):
     immune system  skeleton 

    Find genes that share phenotypes with ISG15           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Isg15tm1Kpk for ISG15

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ISG15
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ISG15

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ISG15
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ISG15

    miRNA
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    miRTarBase miRNAs that target ISG15:
    hsa-mir-146a-5p (MIRT021235), hsa-mir-1 (MIRT023954)

    Block miRNA regulation of human, mouse, rat ISG15 using miScript Target Protectors
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    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat ISG15

    Gene Editing
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    Clone
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    Browse Sino Biological Human cDNA Clones
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    Addgene plasmids for ISG15 

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ISG15_HUMAN, P05161: Cytoplasm. Secreted. Note=Exists in three distinct states: free within the cell, released
    into the extracellular space, or conjugated to target proteins
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    cytosol4
    nucleus2

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IDA--
    GO:0005615extracellular space ----
    GO:0005737cytoplasm ----
    GO:0005829cytosol TAS--

    Find genes that share ontologies with ISG15           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ISG15 About    
    See pathways by source

    SuperPathContained pathways About
    1RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways0.47
    Negative regulators of RIG-I/MDA5 signaling0.42
    RIG-I-like receptor signaling pathway0.47
    2Immune response IFN alpha beta signaling pathway
    Immune response IFN alpha beta signaling pathway0.69
    Interferon alpha/beta signaling0.43
    3Interferon Signaling
    Interferon Signaling0.59
    ISG15 antiviral mechanism0.42
    Cytokine Signaling in Immune system0.59
    Antiviral mechanism by IFN-stimulated genes0.42
    4Type II interferon signaling (IFNG)
    Type II interferon signaling (IFNG)
    5Protein Stability
    Protein Stability


    Find genes that share SuperPaths with ISG15           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    1 Cell Signaling Technology (CST) Pathway for ISG15
        Protein Stability

    1 GeneGo (Thomson Reuters) Pathway for ISG15
        Immune response IFN alpha/beta signaling pathway

    1 BioSystems Pathway for ISG15
        Type II interferon signaling (IFNG)


    4 Reactome Pathways for ISG15
        Interferon alpha/beta signaling
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    Negative regulators of RIG-I/MDA5 signaling
    ISG15 antiviral mechanism


    1 Kegg Pathway  (Kegg details for ISG15):
        RIG-I-like receptor signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ISG15: 
              Antiviral Response in human mouse rat
              Interferons & Receptors in human mouse rat
              Type I Interferon Response in human mouse rat
              JAK / STAT Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ISG15

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ISG15 (P051611, 2, 3 ENSP000003686994) via UniProtKB, MINT, STRING, and/or I2D (see all 125)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PPM1BO756881, 2, 3, ENSP000002824124EBI-746466,EBI-1047039 MINT-2841892 MINT-2841870 I2D: score=2 STRING: ENSP00000282412
    FLNBO753691, 2, 3, ENSP000002959564EBI-746466,EBI-352089 MINT-7288599 MINT-7288590 MINT-7288640 MINT-7288670 I2D: score=1 STRING: ENSP00000295956
    UBA7P412262, 3, ENSP000003332664MINT-68321 I2D: score=6 STRING: ENSP00000333266
    USP18Q9UMW82, 3, ENSP000002157944MINT-66847 I2D: score=5 STRING: ENSP00000215794
    ELF3P785453, ENSP000003526734I2D: score=2 STRING: ENSP00000352673
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007267cell-cell signaling ----
    GO:0016032viral process IEA--
    GO:0019048modulation by virus of host morphology or physiology ----
    GO:0019221cytokine-mediated signaling pathway TAS--
    GO:0019941modification-dependent protein catabolic process IEA--

    Find genes that share ontologies with ISG15           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ISG15

    Selected Novoseek inferred chemical compound relationships for ISG15 gene (see all 12)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    2',5'-oligoadenylate 41.9 2 17156188 (1), 15749911 (1)
    amide 30.6 4 18478335 (1), 20053572 (1)
    cycloheximide 22.9 2 1919073 (1)
    cysteine 11.9 10 18606809 (2), 10030672 (1), 16407192 (1)
    camptothecin 9.2 8 15684817 (5), 11193908 (1)
    lysine 8.87 1 20133869 (1)
    hydrogen 5.49 6 10993253 (1), 11955021 (1), 15213422 (1), 15213429 (1)
    atp 0 5 8550581 (2), 12426315 (1)
    progesterone 0 5 10684803 (3), 17088421 (2)
    methanol 0 1 17525462 (1)



    Find genes that share compounds with ISG15           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for ISG15 gene: 
    NM_005101.3  

    Unigene Cluster for ISG15:

    ISG15 ubiquitin-like modifier
    Hs.458485  [show with all ESTs]
    Unigene Representative Sequence: BQ279256
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000379389(uc001acj.4)
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    Additional mRNA sequence: 

    AY168648.1 BC009507.2 BT007297.1 M13755.1 

    4 DOTS entries:

    DT.417017  DT.100787717  DT.100060240  DT.121453518 

    Selected AceView cDNA sequences (see all 231):

    CK904944 AI537436 AI086993 BU161226 BM055105 BG177492 BQ050582 BQ050884 
    BU956376 BC009507 BU857786 BX950925 BI836784 BF973050 CB126803 AI336331 
    CF529736 BQ437232 CB136953 BI834609 BM716359 AW439384 BU859654 BF684962 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ISG15 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATCTGCGCC
    ISG15 Expression
    About this image


    ISG15 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Ovary (Reproductive System)
             Secondary follicles
     
     Blood (Hematopoietic System)
             Granulocytes Peripheral Blood
    ISG15 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ISG15 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.458485

    UniProtKB/Swiss-Prot: ISG15_HUMAN, P05161
    Tissue specificity: Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons.
    Expressed in neutrophils, monocytes and lymphocytes. Enhanced expression seen in pancreatic adenocarcinoma,
    endometrial cancer, and bladder cancer, as compared to non-cancerous tissue. In bladder cancer, the increase in
    expression exhibits a striking positive correlation with more advanced stages of the disease

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ISG15: 
              Antiviral Response in human mouse rat
              Interferons & Receptors in human mouse rat
              Type I Interferon Response in human mouse rat
              JAK / STAT Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of human and mouse.

    Orthologs for ISG15 gene from Selected species (see all 6)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Isg151 , 5 ISG15 ubiquitin-like modifier1, 5 76.5(n)1
    66.67(a)1
      4 (88.61 cM)5
    1000388821  NM_015783.31  NP_056598.21 
     1561994245 


    ENSEMBL Gene Tree for ISG15 (if available)
    TreeFam Gene Tree for ISG15 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ISG15 gene
    6 SIMAP similar genes for ISG15 using alignment to 1 protein entry:     ISG15_HUMAN:
    UBA52    DKFZp434K0435    UBB    UbC    UBC    UBBP4

    Find genes that share paralogs with ISG15           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    4 SNPs for ISG15    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs593085461,2
    C--948423(+) AACAA-/ACA   
       A
    /CAA
    AAAAA
    2 -- us2k1 cds11NA 2
    rs709495411,2
    C--950117(+) TGAAG-/TAAG  
            
    ACAGC
    1 -- ds50011Minor allele frequency- TAAG:0.00NA 2
    rs19211,2,4
    ----see VAR_0161812 mis40--------
    rs725027441,2
    ----948431(+) CAACA-/CAAAAAAA 1 -- cds10--------

    HapMap Linkage Disequilibrium report for ISG15 (948803 - 949920 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for ISG15 (see all 18):    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv509146CNV Insertion20534489
    dgv14n71CNV Loss21882294
    dgv9n71CNV Loss21882294
    dgv12n71CNV Loss21882294
    dgv10n71CNV Loss21882294
    dgv13n71CNV Loss21882294
    dgv11n71CNV Loss21882294
    nsv871483CNV Loss21882294
    nsv871547CNV Loss21882294
    dgv15n71CNV Loss21882294

    Human Gene Mutation Database (HGMD): ISG15
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing ISG15
    DNA2.0 Custom Variant and Variant Library Synthesis for ISG15

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 147571    OMIM disorders: --

    5 diseases for ISG15:    
    About MalaCards
    mendelian susceptibility to mycobacterial diseases due to complete isg15 deficiency    japanese encephalitis    stomatitis    acute promyelocytic leukemia
    amyotrophic lateral sclerosis

    1 disease from the University of Copenhagen DISEASES database for ISG15:
    Hepatitis C

    Find genes that share disorders with ISG15           About GenesLikeMe

    Selected Novoseek inferred disease relationships for ISG15 gene (see all 23)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vesicular stomatitis 37.3 2 17227866 (1)
    virus infection 34.9 8 17227866 (3), 1370126 (1), 16697044 (1), 10508226 (1)
    influenza 29.5 20 19357168 (7), 20133869 (4), 16009940 (2), 1370126 (1) (see all 6)
    neurodegeneration 29.2 1 18550655 (1)
    liver diseases alcoholic 24.9 2 12436058 (1), 12792671 (1)
    frontotemporal dementia 24.7 2 19223871 (1), 17021754 (1)
    neurodegenerative diseases 24.4 5 2172853 (1), 9228278 (1), 8861020 (1), 12792671 (1)
    amyotrophic lateral sclerosis 22.3 3 19223871 (1), 8861020 (1)
    parkinson disease 15.6 1 11841562 (1)
    bacterial infections 11.2 3 16352599 (1), 16407192 (1)

    Genetic Association Database (GAD): ISG15
    Human Genome Epidemiology (HuGE) Navigator: ISG15 (7 documents)

    Export disorders for ISG15 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ISG15 gene, integrated from 10 sources (see all 246):
    (articles sorted by number of sources associating them with ISG15)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. (PubMed id 3087979)1, 2, 3 Blomstrom D.C.... Knight E. Jr. (J. Biol. Chem. 1986)
    2. Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme. (PubMed id 16428300)1, 2, 9 Takeuchi T.... Yokosawa H. (J. Biochem. 2005)
    3. ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells. (PubMed id 20133869)1, 2, 9 Zhao C....Krug R.M. (Proc. Natl. Acad. Sci. U.S.A. 2010)
    4. Nitrosylation of ISG15 prevents the disulfide bond-mediated dimerization of ISG15 and contributes to effective ISGylation. (PubMed id 18606809)1, 2, 9 Okumura F....Zhang D.E. (J. Biol. Chem. 2008)
    5. Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. (PubMed id 7526157)1, 2, 9 Loeb K.R. and Haas A.L. (Mol. Cell. Biol. 1994)
    6. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. (PubMed id 16009940)1, 2, 9 Zhao C.... Krug R.M. (Proc. Natl. Acad. Sci. U.S.A. 2005)
    7. Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells. (PubMed id 19357168)1, 2, 9 Hsiang T.Y....Krug R.M. (J. Virol. 2009)
    8. Different roles for two ubiquitin-like domains of ISG15 in protein modification. (PubMed id 18356159)1, 2, 9 Chang Y.G....Hu H.Y. (J. Biol. Chem. 2008)
    9. The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein. (PubMed id 15131269)1, 2, 9 Zhao C.... Krug R.M. (Proc. Natl. Acad. Sci. U.S.A. 2004)
    10. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. (PubMed id 8550581)1, 2, 9 Narasimhan J.... Haas A.L. (J. Biol. Chem. 1996)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9636 HGNC: 4053 AceView: G1P2 Ensembl:ENSG00000187608 euGenes: HUgn9636
    ECgene: ISG15 Kegg: 9636 H-InvDB: ISG15

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ISG15 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ISG15 gene:
    Search GeneIP for patents involving ISG15

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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