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ISG15
HPA
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  • ISG15
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
GENERAL INFORMATIONi

General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.

Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

ISG15
Synonyms G1P2, IFI15, UCRP
Gene descriptioni

Full gene name according to HGNC.

ISG15 ubiquitin like modifier
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

Disease related genes
Human disease related genes
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Secreted, Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi

Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.

Chromosome 1
Cytoband p36.33
Chromosome location (bp) 1001138 - 1014540
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

3
Ensembl ENSG00000187608 (version 109)
Entrez gene 9636
HGNC HGNC:4053
UniProt P05161 (UniProt - Evidence at protein level)
neXtProt NX_P05161
GeneCards ISG15
Antibodypedia ISG15 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

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 1. 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 2. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses 3. Can also isgylate: EIF2AK2/PKR which results in its activation, RIGI 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 thereby 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. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL 4.... show less
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway
Gene summary (Entrez)i

Useful information about the gene from Entrez

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]... show less
PROTEIN INFORMATIONi

The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.

The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.

The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.

The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)
Transmembrane regions
(predicted)
ISG15-201
ENSP00000485313
ENST00000624652
A0A096LNZ9
[Direct mapping] Ubiquitin-like protein ISG15
Show all
Predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Immune system diseases
   Primary immunodeficiency
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0005515 [protein binding]
Show all
143 aa
15.6 kDa
No 0
ISG15-202
ENSP00000485643
ENST00000624697
A0A096LPJ4
[Direct mapping] Ubiquitin-like protein ISG15
Show all
Predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Human disease related genes
   Immune system diseases
   Primary immunodeficiency
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0005515 [protein binding]
Show all
157 aa
17 kDa
No 0
ISG15-203
ENSP00000496832
ENST00000649529
P05161
[Direct mapping] Ubiquitin-like protein ISG15
Show all
Predicted secreted proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Disease related genes
Human disease related genes
   Immune system diseases
   Primary immunodeficiency
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0002376 [immune system process]
GO:0003735 [structural constituent of ribosome]
GO:0005178 [integrin binding]
GO:0005515 [protein binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0007229 [integrin-mediated signaling pathway]
GO:0009615 [response to virus]
GO:0009617 [response to bacterium]
GO:0019941 [modification-dependent protein catabolic process]
GO:0022627 [cytosolic small ribosomal subunit]
GO:0030501 [positive regulation of bone mineralization]
GO:0031386 [protein tag]
GO:0031397 [negative regulation of protein ubiquitination]
GO:0031625 [ubiquitin protein ligase binding]
GO:0032020 [ISG15-protein conjugation]
GO:0032461 [positive regulation of protein oligomerization]
GO:0032649 [regulation of interferon-gamma production]
GO:0032728 [positive regulation of interferon-beta production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032733 [positive regulation of interleukin-10 production]
GO:0034340 [response to type I interferon]
GO:0042742 [defense response to bacterium]
GO:0045071 [negative regulation of viral genome replication]
GO:0045087 [innate immune response]
GO:0045648 [positive regulation of erythrocyte differentiation]
GO:0051607 [defense response to virus]
GO:0060339 [negative regulation of type I interferon-mediated signaling pathway]
GO:0070585 [protein localization to mitochondrion]
Show all
165 aa
17.9 kDa
No 0

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