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ISG15 ISG15 ubiquitin-like modifier [ Homo sapiens (human) ]

Gene ID: 9636, updated on 26-May-2016
Official Symbol
ISG15provided by HGNC
Official Full Name
ISG15 ubiquitin-like modifierprovided by HGNC
Primary source
HGNC:HGNC:4053
See related
Ensembl:ENSG00000187608 HPRD:00958; MIM:147571; Vega:OTTHUMG00000040777
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
G1P2; IP17; UCRP; IFI15; IMD38; hUCRP
Summary
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]
Orthologs
Location:
1p36.33
Exon count:
2
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 1 NC_000001.11 (1013467..1014540)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (948847..949920)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene hes family bHLH transcription factor 4 Neighboring gene ribosomal protein L39 pseudogene 12 Neighboring gene agrin Neighboring gene uncharacterized LOC100288175

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag HERC5 restricts HIV-1 Gag particle production by a mechanism dependent on its E3 ligase activity. This restriction correlates with the conjugation of ISG15 to Gag by HERC5 PubMed
gag ISG15 inhibits budding of HIV-1 by disrupting the association between Vps4 and the Gag budding complex PubMed
Tat tat HIV-1 and the viral protein Tat modulate the expression of ISG15 ubiquitin-like modifier (ISG15) in immature dendritic cells and monocyte-derived macrophages PubMed
tat Microarray analysis indicates HIV-1 Tat upregulates the interferon-responsive gene expression of many proteins, including ISG15, in immature dendritic cells, an effect that likely facilitates the expansion of HIV-1 infection PubMed
Vpr vpr HIV-1 Vpr upregulates the expression of ISG15 in human monocyte-derived macrophages PubMed
Vpu vpu The expression of ISG15 ubiquitin-like modifier is enhanced in Vpu-deficient HIV-1-infected cells as compared to that in wild-type-infected cells PubMed

Go to the HIV-1, Human Interaction Database

  • Antiviral mechanism by IFN-stimulated genes, organism-specific biosystem (from REACTOME)
    Antiviral mechanism by IFN-stimulated genes, organism-specific biosystemThe ISG proteins generated by IFN pathways plays key roles in the induction of innate and adaptive immune responses.
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • DNA Damage Bypass, organism-specific biosystem (from REACTOME)
    DNA Damage Bypass, organism-specific biosystemIn addition to various processes for removing lesions from the DNA, cells have developed specific mechanisms for tolerating unrepaired damage during the replication of the genome. These mechanisms ar...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Host Interactions with Influenza Factors, organism-specific biosystem (from REACTOME)
    Host Interactions with Influenza Factors, organism-specific biosystemInfection of a human host cell with influenza virus triggers an array of host processes that interfere with viral replication, notably the production of type I interferon. The viral NS1 protein plays...
  • ISG15 antiviral mechanism, organism-specific biosystem (from REACTOME)
    ISG15 antiviral mechanism, organism-specific biosystemInterferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. On...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Influenza Infection, organism-specific biosystem (from REACTOME)
    Influenza Infection, organism-specific biosystemFor centuries influenza epidemics have plagued man, and influenza was probably the disease described by Hippocrates in 412 BC. Today it remains a major cause of morbidity and mortality worldwide with...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Interferon Signaling, organism-specific biosystem (from REACTOME)
    Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
  • Interferon alpha/beta signaling, organism-specific biosystem (from REACTOME)
    Interferon alpha/beta signaling, organism-specific biosystemType I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, wher...
  • NS1 Mediated Effects on Host Pathways, organism-specific biosystem (from REACTOME)
    NS1 Mediated Effects on Host Pathways, organism-specific biosystemViral NS1 protein is a nuclear, dimeric protein that is highly expressed in infected cells and has dsRNA-binding activity. The RNA-binding domain lies within the N-terminal portion of the protein. Th...
  • Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystem (from REACTOME)
    Negative regulators of RIG-I/MDA5 signaling, organism-specific biosystemAs with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune...
  • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystem (from REACTOME)
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystemRIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. F...
  • Termination of translesion DNA synthesis, organism-specific biosystem (from REACTOME)
    Termination of translesion DNA synthesis, organism-specific biosystemThe initiation and extent of translesion DNA synthesis (TLS) has to be tightly controlled in order to limit TLS-induced mutagenesis, caused by the low fidelity of TLS-participating DNA polymerases. S...
  • Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template, organism-specific biosystem (from REACTOME)
    Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template, organism-specific biosystemUbiquitous environmental and endogenous genotoxic agents cause DNA lesions that can interfere with normal DNA metabolism including DNA replication, eventually resulting in mutations that lead to carc...
  • Type II interferon signaling (IFNG), organism-specific biosystem (from WikiPathways)
    Type II interferon signaling (IFNG), organism-specific biosystemAdapted from Raza et al. (2008). This pathway is initiated by IFNG binding to its receptor and a subsequent phosphorylation cascade involving a number of the JAK and STAT family of proteins. Several ...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein tag IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
ISG15-protein conjugation IDA
Inferred from Direct Assay
more info
PubMed 
ISG15-protein conjugation IMP
Inferred from Mutant Phenotype
more info
PubMed 
defense response to bacterium IMP
Inferred from Mutant Phenotype
more info
PubMed 
defense response to virus IMP
Inferred from Mutant Phenotype
more info
PubMed 
modification-dependent protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of type I interferon production TAS
Traceable Author Statement
more info
 
negative regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of erythrocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
regulation of interferon-gamma production IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to type I interferon IDA
Inferred from Direct Assay
more info
PubMed 
translesion synthesis TAS
Traceable Author Statement
more info
 
type I interferon signaling pathway TAS
Traceable Author Statement
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
extracellular region IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
Preferred Names
ubiquitin-like protein ISG15
Names
interferon, alpha-inducible protein (clone IFI-15K)
interferon-induced 17-kDa/15-kDa protein
interferon-stimulated protein, 15 kDa
ubiquitin cross-reactive protein

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033033.1 RefSeqGene

    Range
    5001..6074
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005101.3NP_005092.1  ubiquitin-like protein ISG15 precursor

    See identical proteins and their annotated locations for NP_005092.1

    Status: REVIEWED

    Source sequence(s)
    AL645608, BC009507, BM712238, BU161226, M13755
    Consensus CDS
    CCDS6.1
    UniProtKB/Swiss-Prot
    P05161
    Related
    ENSP00000368699, OTTHUMP00000038464, ENST00000379389, OTTHUMT00000097989
    Conserved Domains (3) summary
    cd01792
    Location:180
    ISG15_repeat1; ISG15 ubiquitin-like protein, first repeat of 2
    smart00213
    Location:82153
    UBQ; Ubiquitin homologues
    cl00155
    Location:84157
    UBQ; Ubiquitin-like proteins

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p2 Primary Assembly

    Range
    1013467..1014540
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 Alternate CHM1_1.1

    Range
    935863..936936
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)