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Aliases for ISG15 Gene

Aliases for ISG15 Gene

  • ISG15 Ubiquitin-Like Modifier 2 3
  • G1P2 3 4 6
  • Interferon, Alpha-Inducible Protein (Clone IFI-15K) 2 3
  • Ubiquitin Cross-Reactive Protein 3 4
  • IFI15 3 6
  • HUCRP 3 4
  • UCRP 3 4
  • IP17 3 4
  • Interferon-Induced 17-KDa/15-KDa Protein 3
  • Interferon-Stimulated Protein, 15 KDa 3
  • Interferon-Induced 15 KDa Protein 4
  • Interferon-Induced 17 KDa Protein 4
  • Ubiquitin-Like Protein ISG15 3
  • IMD38 3

External Ids for ISG15 Gene

Previous HGNC Symbols for ISG15 Gene

  • G1P2

Previous GeneCards Identifiers for ISG15 Gene

  • GC01P000478
  • GC01P000938
  • GC01P000220

Summaries for ISG15 Gene

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 immunodeficiency 38 and mendelian susceptibility to mycobacterial diseases due to complete isg15 deficiency. Among its related pathways are Interferon Signaling and Interferon Signaling. GO annotations related to this gene include protein tag.

UniProtKB/Swiss-Prot for ISG15 Gene

  • 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ISG15 Gene

Genomics for ISG15 Gene

Regulatory Elements for ISG15 Gene

Genomic Location for ISG15 Gene

Start:
1,001,138 bp from pter
End:
1,014,541 bp from pter
Size:
13,404 bases
Orientation:
Plus strand

Genomic View for ISG15 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ISG15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ISG15 Gene

Proteins for ISG15 Gene

  • Protein details for ISG15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P05161-ISG15_HUMAN
    Recommended name:
    Ubiquitin-like protein ISG15
    Protein Accession:
    P05161
    Secondary Accessions:
    • Q5SVA4
    • Q7Z2G2
    • Q96GF0

    Protein attributes for ISG15 Gene

    Size:
    165 amino acids
    Molecular mass:
    17888 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for ISG15 Gene

neXtProt entry for ISG15 Gene

Proteomics data for ISG15 Gene at MOPED

Post-translational modifications for ISG15 Gene

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

Other Protein References for ISG15 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for ISG15 Gene

Domains for ISG15 Gene

Protein Domains for ISG15 Gene

Suggested Antigen Peptide Sequences for ISG15 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P05161

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).
  • Contains 2 ubiquitin-like domains.
genes like me logo Genes that share domains with ISG15: view

No data available for Gene Families for ISG15 Gene

Function for ISG15 Gene

Molecular function for ISG15 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction: Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including certain genotoxic stresses.

Gene Ontology (GO) - Molecular Function for ISG15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16189514
GO:0031386 protein tag IEA --
genes like me logo Genes that share ontologies with ISG15: view
genes like me logo Genes that share phenotypes with ISG15: view

Animal Models for ISG15 Gene

MGI Knock Outs for ISG15:

miRNA for ISG15 Gene

miRTarBase miRNAs that target ISG15

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for ISG15 Gene

Localization for ISG15 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ISG15 Gene

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
Jensen Localization Image for ISG15 Gene COMPARTMENTS Subcellular localization image for ISG15 gene
Compartment Confidence
extracellular 5
cytosol 4
nucleus 2

Gene Ontology (GO) - Cellular Components for ISG15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IDA 22859821
GO:0005654 nucleoplasm TAS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with ISG15: view

Pathways for ISG15 Gene

genes like me logo Genes that share pathways with ISG15: view

Pathways by source for ISG15 Gene

1 KEGG pathway for ISG15 Gene
1 GeneGo (Thomson Reuters) pathway for ISG15 Gene

Gene Ontology (GO) - Biological Process for ISG15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair TAS --
GO:0016032 viral process IEA --
GO:0019221 cytokine-mediated signaling pathway TAS --
GO:0019941 modification-dependent protein catabolic process IEA --
GO:0019985 translesion synthesis TAS --
genes like me logo Genes that share ontologies with ISG15: view

Compounds for ISG15 Gene

(12) Novoseek inferred chemical compound relationships for ISG15 Gene

Compound -log(P) Hits PubMed IDs
2,5-oligoadenylate 41.9 2
amide 30.6 2
cycloheximide 22.9 1
cysteine 11.9 4
camptothecin 9.2 6
genes like me logo Genes that share compounds with ISG15: view

Transcripts for ISG15 Gene

mRNA/cDNA for ISG15 Gene

Unigene Clusters for ISG15 Gene

ISG15 ubiquitin-like modifier:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ISG15 Gene

No ASD Table

Relevant External Links for ISG15 Gene

GeneLoc Exon Structure for
ISG15
ECgene alternative splicing isoforms for
ISG15

Expression for ISG15 Gene

mRNA expression in normal human tissues for ISG15 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ISG15 Gene

This gene is overexpressed in Brain - Substantia nigra (8.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ISG15 Gene

SOURCE GeneReport for Unigene cluster for ISG15 Gene Hs.458485

mRNA Expression by UniProt/SwissProt for ISG15 Gene

P05161-ISG15_HUMAN
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.
genes like me logo Genes that share expressions with ISG15: view

Orthologs for ISG15 Gene

This gene was present in the common ancestor of mammals.

Orthologs for ISG15 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ISG15 36
  • 98 (a)
OneToMany
ISG15 36
  • 98 (a)
OneToMany
LOC100609237 35
  • 99.39 (n)
  • 98.18 (a)
cow
(Bos Taurus)
Mammalia ISG15 35
  • 76.41 (n)
  • 66.88 (a)
ISG15 36
  • 67 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ISG15 35
  • 77.42 (n)
  • 70.32 (a)
ISG15 36
  • 66 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Isg15 35
  • 76.5 (n)
  • 66.67 (a)
Isg15 16
Isg15 36
  • 64 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ISG15 36
  • 46 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Isg15 35
  • 73.25 (n)
  • 64.33 (a)
Species with no ortholog for ISG15:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for ISG15 Gene

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

Paralogs for ISG15 Gene

Selected SIMAP similar genes for ISG15 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with ISG15: view

No data available for Paralogs for ISG15 Gene

Variants for ISG15 Gene

Sequence variations from dbSNP and Humsavar for ISG15 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type MAF
rs1921 - 1,014,228(+) TCTGA(A/C/G)CATCC missense, reference
rs8997 -- 1,014,274(+) GAGGT(A/G)CGGCT reference, synonymous-codon
rs15842 -- 1,013,541(-) GGCAC(A/G)AGCTC utr-variant-5-prime
rs1126573 -- 1,013,990(+) GCTGG(A/G)ACCTG missense, reference
rs1126625 -- 1,014,088(+) AAGAT(C/T)GGCGT reference, synonymous-codon

Structural Variations from Database of Genomic Variants (DGV) for ISG15 Gene

Variant ID Type Subtype PubMed ID
dgv3e1 CNV Complex 17122850
essv4734 CNV CNV 17122850
nsv10161 CNV Gain+Loss 18304495
essv2408 CNV CNV 17122850
nsv517709 CNV Gain+Loss 19592680
nsv428334 CNV Gain 18775914
dgv2n67 CNV Gain 20364138
nsv871883 CNV Gain+Loss 21882294
dgv9n71 CNV Loss 21882294
nsv871547 CNV Loss 21882294
dgv10n71 CNV Loss 21882294
dgv11n71 CNV Loss 21882294
dgv12n71 CNV Loss 21882294
dgv13n71 CNV Loss 21882294
nsv871483 CNV Loss 21882294
nsv509146 CNV Insertion 20534489
dgv14n71 CNV Loss 21882294
dgv15n71 CNV Loss 21882294

Relevant External Links for ISG15 Gene

HapMap Linkage Disequilibrium report
ISG15
Human Gene Mutation Database (HGMD)
ISG15

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ISG15 Gene

Disorders for ISG15 Gene

UniProtKB/Swiss-Prot

ISG15_HUMAN
  • Immunodeficiency 38 (IMD38) [MIM:616126]: A primary immunodeficiency predisposing individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines. Patients are also susceptible to Salmonella and Mycobacterium tubercolosis infections. {ECO:0000269 PubMed:22859821}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for ISG15 Gene

(23) Novoseek inferred disease relationships for ISG15 Gene

Disease -log(P) Hits PubMed IDs
vesicular stomatitis 37.3 1
virus infection 34.9 6
influenza 29.5 16
neurodegeneration 29.2 1
liver diseases alcoholic 24.9 2

Relevant External Links for ISG15

Genetic Association Database (GAD)
ISG15
Human Genome Epidemiology (HuGE) Navigator
ISG15
genes like me logo Genes that share disorders with ISG15: view

Publications for ISG15 Gene

  1. Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues. (PMID: 7490683) Lowe J. … Mayer R.J. (J. Pathol. 1995) 3 4 23
  2. Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern. (PMID: 7526157) Loeb K.R. … Haas A.L. (Mol. Cell. Biol. 1994) 3 4 23
  3. Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin. (PMID: 8550581) Narasimhan J. … Haas A.L. (J. Biol. Chem. 1996) 3 4 23
  4. The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein. (PMID: 15131269) Zhao C. … Krug R.M. (Proc. Natl. Acad. Sci. U.S.A. 2004) 3 4 23
  5. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. (PMID: 16009940) Zhao C. … Krug R.M. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 4 23

Products for ISG15 Gene

  • Addgene plasmids for ISG15

Sources for ISG15 Gene

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