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

Summary

Official Symbol: ISG15provided by HGNC
Official Full Name: ISG15 ubiquitin like modifierprovided by HGNC
Primary source: HGNC:HGNC:4053
See related: Ensembl:ENSG00000187608 MIM:147571; AllianceGenome:HGNC:4053
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]
Expression: Broad expression in salivary gland (RPKM 43.3), spleen (RPKM 35.3) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.33

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (1013497..1014540)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (443628..444671)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (948877..949920)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ISG15 accelerates acute kidney injury and the subsequent AKI-to-CKD transition by promoting TGFbetaR1 ISGylation.
Title: ISG15 accelerates acute kidney injury and the subsequent AKI-to-CKD transition by promoting TGFβR1 ISGylation.
Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.
Title: Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.
ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.
Title: ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.
Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.
Title: Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.
ISG15-USP18 Dysregulation by Oxidative Stress Promotes IFN-gamma Secretion from CD8+ T Cells in Vitiligo.
Title: ISG15-USP18 Dysregulation by Oxidative Stress Promotes IFN-γ Secretion from CD8+ T Cells in Vitiligo.
Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.
Title: Case Report: ISG15 deficiency caused by novel variants in two families and effective treatment with Janus kinase inhibition.
A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia.
Title: A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia.
ISG15: its roles in SARS-CoV-2 and other viral infections.
Title: ISG15: its roles in SARS-CoV-2 and other viral infections.
ISG15 and ISGylation modulates cancer stem cell-like characteristics in promoting tumor growth of anaplastic thyroid carcinoma.
Title: ISG15 and ISGylation modulates cancer stem cell-like characteristics in promoting tumor growth of anaplastic thyroid carcinoma.
The role of interferon-stimulated gene 15 in the occurence and progression of cervical squamous cell carcinoma.
Title: The role of interferon-stimulated gene 15 in the occurence and progression of cervical squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (184)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency MedGen: C4015293 OMIM: 616126 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 dendritic cells	PubMed
	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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC84353P2 (e-PCR)
- UniSTS:273443

G62009 (e-PCR)
- UniSTS:139083

SHGC-74128 (e-PCR)
- UniSTS:57253

PMC135632P2 (e-PCR)
- UniSTS:270759

RH66824 (e-PCR)
- UniSTS:91321

SHGC-74084 (e-PCR)
- UniSTS:77499

RH80369 (e-PCR)
- UniSTS:87782

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tag activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tag activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tag activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in ISG15-protein conjugation	IBA Inferred from Biological aspect of Ancestor more info
involved_in ISG15-protein conjugation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within ISG15-protein conjugation	IEA Inferred from Electronic Annotation more info
involved_in ISG15-protein conjugation	IEA Inferred from Electronic Annotation more info
involved_in ISG15-protein conjugation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in defense response to bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune system process	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in integrin-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in modification-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within modification-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of type I interferon-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of viral genome replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of bone mineralization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of bone mineralization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-10 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of multicellular organismal process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein oligomerization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type II interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to mitochondrion	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of immune system process	IEA Inferred from Electronic Annotation more info
involved_in regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to type I interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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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

NCBI Reference Sequences (RefSeq)

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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

NG_033033.2 RefSeqGene

Range

17360..18403

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1231

mRNA and Protein(s)

NM_005101.4 → NP_005092.1 ubiquitin-like protein ISG15

See identical proteins and their annotated locations for NP_005092.1

Status: REVIEWED

Source sequence(s)

AL645608, BC009507, BU161226, M13755

Consensus CDS

CCDS6.1

UniProtKB/Swiss-Prot

P05161, Q5SVA4, Q7Z2G2, Q96GF0

UniProtKB/TrEMBL

A0A096LPJ4

Related

ENSP00000496832.1, ENST00000649529.1

Conserved Domains (3) summary

cd01792
Location:1 → 80

ISG15_repeat1; ISG15 ubiquitin-like protein, first repeat of 2

smart00213
Location:82 → 153

UBQ; Ubiquitin homologues

cl00155
Location:84 → 157

UBQ; Ubiquitin-like proteins