USP18 ubiquitin specific peptidase 18 [Homo sapiens (human)] - Gene

Summary

Official Symbol: USP18provided by HGNC
Official Full Name: ubiquitin specific peptidase 18provided by HGNC
Primary source: HGNC:HGNC:12616
See related: Ensembl:ENSG00000184979 MIM:607057; AllianceGenome:HGNC:12616
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ISG43; UBP43; PTORCH2
Summary: The protein encoded by this gene belongs to the ubiquitin-specific proteases (UBP) family of enzymes that cleave ubiquitin from ubiquitinated protein substrates. It is highly expressed in liver and thymus, and is localized to the nucleus. This protein efficiently cleaves only ISG15 (a ubiquitin-like protein) fusions, and deletion of this gene in mice results in a massive increase of ISG15 conjugates in tissues, indicating that this protein is a major ISG15-specific protease. Mice lacking this gene are also hypersensitive to interferon, suggesting a function of this protein in downregulating interferon responses, independent of its isopeptidase activity towards ISG15. [provided by RefSeq, Sep 2011]
Expression: Ubiquitous expression in fat (RPKM 6.5), spleen (RPKM 6.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.21

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (18150170..18177397)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (18822080..18849307)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (18632937..18660164)

Chromosome 22 - NC_000022.11 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Genome-wide DNA methylation analysis implicates enrichment of interferon pathway in African American patients with Systemic Lupus Erythematosus and European Americans with lupus nephritis.
Title: Genome-wide DNA methylation analysis implicates enrichment of interferon pathway in African American patients with Systemic Lupus Erythematosus and European Americans with lupus nephritis.
Tumor-promoting action of ubiquitin protease 43 in gastric cancer progression through deubiquitination and stabilization of stress-inducible phosphoprotein 1.
Title: Tumor-promoting action of ubiquitin protease 43 in gastric cancer progression through deubiquitination and stabilization of stress-inducible phosphoprotein 1.
USP18 promotes innate immune responses and apoptosis in influenza A virus-infected A549 cells via cGAS-STING pathway.
Title: USP18 promotes innate immune responses and apoptosis in influenza A virus-infected A549 cells via cGAS-STING pathway.
UBP43 promotes epithelial ovarian carcinogenesis via activation of beta-catenin signaling pathway.
Title: UBP43 promotes epithelial ovarian carcinogenesis via activation of β-catenin signaling pathway.
USP18 regulates the malignant phenotypes of glioblastoma stem cells.
Title: USP18 regulates the malignant phenotypes of glioblastoma stem cells.
Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis.
Title: Expansion of interferon inducible gene pool via USP18 inhibition promotes cancer cell pyroptosis.
Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.
Title: Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.
USP18 contributes to the proliferation and migration of ovarian cancer cells by regulating the AKT/mTOR signaling pathway.
Title: USP18 contributes to the proliferation and migration of ovarian cancer cells by regulating the AKT/mTOR signaling pathway.
A partial form of inherited human USP18 deficiency underlies infection and inflammation.
Title: A partial form of inherited human USP18 deficiency underlies infection and inflammation.

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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
Pseudo-TORCH syndrome 2 MedGen: C4479376 OMIM: 617397 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 and the viral protein Tat modulate the expression of ubiquitin specific peptidase 18 (USP18; ISG43) in immature dendritic cells and monocyte-derived macrophages	PubMed
Vpr	vpr	HIV-1 Vpr upregulates the gene expression of USP18 in human monocyte-derived dendritic cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ISG15-specific peptidase activity	EXP Inferred from Experiment more info	PubMed
enables cysteine-type deubiquitinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type deubiquitinase activity	TAS Traceable Author Statement more info
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in antiviral innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of type I interferon-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein deubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to stilbenoid	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: ubl carboxyl-terminal hydrolase 18

Names: 43 kDa ISG15-specific protease; ISG15-specific-processing protease; ubiquitin specific protease 18; ubl thioesterase 18; ubl thiolesterase 18

NP_059110.2

EC 3.4.19.12

XP_006724137.1

EC 3.4.19.12

XP_054181027.1

EC 3.4.19.12

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.

mRNA and Protein(s)

NM_017414.4 → NP_059110.2 ubl carboxyl-terminal hydrolase 18

See identical proteins and their annotated locations for NP_059110.2

Status: VALIDATED

Source sequence(s)

AC008079

Consensus CDS

CCDS13752.1

UniProtKB/Swiss-Prot

Q53Y90, Q6IAD9, Q9NY71, Q9UMW8

UniProtKB/TrEMBL

A0A8V8TMN0

Related

ENSP00000215794.7, ENST00000215794.8

Conserved Domains (1) summary

pfam00443
Location:55 → 367

UCH; Ubiquitin carboxyl-terminal hydrolase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

18150170..18177397

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006724074.4 → XP_006724137.1 ubl carboxyl-terminal hydrolase 18 isoform X1

Conserved Domains (2) summary

cd02257
Location:60 → 294

Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...

pfam00443
Location:4 → 293

UCH; Ubiquitin carboxyl-terminal hydrolase