ISG15 (ISG15 ubiquitin like modifier)

Gene

• Entrez ID: 9636
• Gene name: ISG15 ubiquitin like modifier
• Gene symbol: ISG15
• Synonyms: G1P2, IFI15, IMD38, IP17, UCRP, hUCRP
• Chromosome: 1
• Chromosome location: 1p36.33
• 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 ac

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs672601312	G>A,T	Uncertain-significance, pathogenic	Stop gained, coding sequence variant, missense variant
rs672601345	->G	Pathogenic	Coding sequence variant, frameshift variant
rs786201005	C>T	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021235	hsa-miR-146a-5p	Microarray	18057241
MIRT023954	hsa-miR-1-3p	Microarray	18668037

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005178	Function	Integrin binding	IPI	29100055
GO:0005515	Function	Protein binding	IPI	16189514, 16872604, 17597759, 18305167, 19270716, 20133869, 21245344, 21266548, 21808041, 25307056, 25416956, 28438633, 28931677, 30644842, 31515488, 32296183, 32814053, 32845033
GO:0005576	Component	Extracellular region	IDA	22859821
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0007229	Process	Integrin-mediated signaling pathway	IDA	29100055
GO:0016032	Process	Viral process	IEA
GO:0016567	Process	Protein ubiquitination	IBA	21873635
GO:0019941	Process	Modification-dependent protein catabolic process	IBA	21873635
GO:0019985	Process	Translesion synthesis	TAS
GO:0022627	Component	Cytosolic small ribosomal subunit	IBA	21873635
GO:0030501	Process	Positive regulation of bone mineralization	ISS
GO:0031386	Function	Protein tag	IBA	21873635
GO:0031397	Process	Negative regulation of protein ubiquitination	IDA	18305167
GO:0031625	Function	Ubiquitin protein ligase binding	IBA	21873635
GO:0032020	Process	ISG15-protein conjugation	IBA	21873635
GO:0032020	Process	ISG15-protein conjugation	IDA	16122702, 21543490
GO:0032020	Process	ISG15-protein conjugation	IMP	22859821
GO:0032480	Process	Negative regulation of type I interferon production	TAS
GO:0032609	Process	Interferon-gamma production	IDA	29100055
GO:0032613	Process	Interleukin-10 production	IDA	29100055
GO:0032649	Process	Regulation of interferon-gamma production	IMP	22859821
GO:0034340	Process	Response to type I interferon	IDA	22859821
GO:0042742	Process	Defense response to bacterium	IMP	22859821
GO:0045071	Process	Negative regulation of viral genome replication	IMP	19357168
GO:0045648	Process	Positive regulation of erythrocyte differentiation	IEA
GO:0051607	Process	Defense response to virus	IMP	19357168
GO:0060337	Process	Type I interferon signaling pathway	TAS

Other IDs

• MIM: 147571
• HGNC: 4053
• e!Ensembl: ENSG00000187608

Protein

• UniProt ID: P05161
• Protein name: Ubiquitin-like protein ISG15 (Interferon-induced 15 kDa protein) (Interferon-induced 17 kDa protein) (IP17) (Ubiquitin cross-reactive protein) (hUCRP)
• Protein 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 (PubMed:27564865, PubMed:39465252). IS
• PDB: 1Z2M, 2HJ8, 3PHX, 3PSE, 3R66, 3RT3, 3SDL, 5TL6, 5W8T, 5W8U, 6BI8, 6FFA, 6XA9, 7RBS, 7S6P, 8OIF, 8SE9, 8SEA, 8SEB, 8SV8
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00240	ubiquitin	5 → 78	Ubiquitin family	Domain
  PF00240	ubiquitin	84 → 155	Ubiquitin family	Domain

• Sequence:

  MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPL
  ASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDD
  LFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS

• Sequence length: 165

Pathways

KEGG:

RIG-I-like receptor signaling pathway
Human papillomavirus infection
Epstein-Barr virus infection
Coronavirus disease - COVID-19

Reactome:

ISG15 antiviral mechanism
NS1 Mediated Effects on Host Pathways
DDX58/IFIH1-mediated induction of interferon-alpha/beta
Termination of translesion DNA synthesis
Interferon alpha/beta signaling
Negative regulators of DDX58/IFIH1 signaling

Associated diseases

Unknown
Disease name	Disease term	dbSNP ID	References
Immunodeficiency, with basal ganglia calcification	IMMUNODEFICIENCY 38 WITH BASAL GANGLIA CALCIFICATION		22859821, 25307056, 23579383
Immunologic deficiency syndromes	Immunologic Deficiency Syndromes
Involutional depression	Involutional Depression		29175309
Involutional paraphrenia	Involutional paraphrenia		29175309
Liver carcinoma	Liver carcinoma		28919514
Mental depression	Major Depressive Disorder	rs587778876, rs587778877	29175309
Psychosis	Psychosis, Involutional		29175309