USP18 ubiquitin specific peptidase 18 [Homo sapiens] - Gene

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Summary

Official Symbol: USP18provided by HGNC
Official Full Name: ubiquitin specific peptidase 18provided by HGNC
Primary source: HGNC:12616
See related: Ensembl:ENSG00000184979; HPRD:06136; MIM:607057; Vega:OTTHUMG00000150104
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
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]

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Genomic context

Location :: 22q11.21

Sequence :: Chromosome: 22; NC_000022.10 (18632758..18660164)

See USP18 in Epigenomics, MapViewer

Chromosome 22 - NC_000022.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

the existence of an N-terminal truncated isoform of USP18, whose expression is controlled on translational level by two independent mechanisms providing translational flexibility
Title: Two independent mechanisms promote expression of an N-terminal truncated USP18 isoform with higher DeISGylation activity in the nucleus.
Inhibition of R. conorii-induced ISG15 by RNA interference results in significant increase in the extent of rickettsial replication, whereas UBP43 knockdown yields a reciprocal inhibitory effect.
Title: Rickettsia conorii infection stimulates the expression of ISG15 and ISG15 protease UBP43 in human microvascular endothelial cells.
a model in which Usp18 inhibition promotes up-regulation of miR-7, which in turn inhibits EGFR expression and the tumorigenic activity of cancer cells.
Title: Usp18 regulates epidermal growth factor (EGF) receptor expression and cancer cell survival via microRNA-7.
Findings define the ubiquitin protease UBP43 as a novel candidate drug target for APL treatment.
Title: Blockade of the ubiquitin protease UBP43 destabilizes transcription factor PML/RARα and inhibits the growth of acute promyelocytic leukemia.
Findings suggest that USP18 may significantly limit operation of the extrinsic apoptotic pathway triggered by type I IFN and drugs.
Title: Identification of USP18 as an important regulator of the susceptibility to IFN-alpha and drug-induced apoptosis.
Epstein-Barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma
Title: Epstein-Barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma.
Ubp43 deficiency increases the resistance to oncogenic transformation by BCR-ABL
Title: Ubp43 regulates BCR-ABL leukemogenesis via the type 1 interferon receptor signaling.
UBP43 protein levels are regulated by proteolysis via the SCFSkp2 ubiquitin ligase
Title: The ISG15 isopeptidase UBP43 is regulated by proteolysis via the SCFSkp2 ubiquitin ligase.

Submit: New GeneRIF Correction

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9UMW8	P48551	IFNAR2	HPRD	PubMed
Q9UMW8	P05161	ISG15	HPRD	PubMed
BioGRID:116430	BioGRID:114995	ISG15	BioGRID	PubMed	Two-hybrid
BioGRID:116430	BioGRID:119727	KDM3B	BioGRID	PubMed	Affinity Capture-MS
BioGRID:116430	BioGRID:110721	MYL6	BioGRID	PubMed	Affinity Capture-MS
BioGRID:116430	BioGRID:110894	NME1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:116430	BioGRID:112393	SKP2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:116430	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:116430	BioGRID:131885	USP41	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
cysteine-type peptidase activity	IEA Inferred from Electronic Annotation more info
peptidase activity	IEA Inferred from Electronic Annotation more info
ubiquitin thiolesterase activity	IEA Inferred from Electronic Annotation more info
ubiquitin-specific protease activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
proteolysis	IEA Inferred from Electronic Annotation more info
regulation of type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info
type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info
ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: ubl carboxyl-terminal hydrolase 18

Names: ubl carboxyl-terminal hydrolase 18; hUBP43; ubl thioesterase 18; ubl thiolesterase 18; 43 kDa ISG15-specific protease; ubiquitin specific protease 18; ISG15-specific-processing protease

NP_059110.2

EC 3.1.2.-

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NCBI Reference Sequences (RefSeq)

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_017414.3 → NP_059110.2 ubl carboxyl-terminal hydrolase 18

Status: VALIDATED

Source sequence(s)

AC008079

Consensus CDS

CCDS13752.1

UniProtKB/TrEMBL

Q53Y90

UniProtKB/Swiss-Prot

Q9UMW8

Related

ENSP00000215794, OTTHUMP00000196334, ENST00000215794, OTTHUMT00000316368

Conserved Domains (2) summary

cl02553
Location:53 – 372
Blast Score: 447

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:53 – 367
Blast Score: 377

UCH; Ubiquitin carboxyl-terminal hydrolase

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000022.10 Reference GRCh37.p5 Primary Assembly

Range

18632758..18660164

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000154.1 Alternate HuRef

Range

2445183..2472579

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008079.24 (80962..108369)	None
genomic	CH471193.1	EAW57790.1
		EAW57791.1
mRNA	AF176642.2	AAD49967.1
mRNA	AI222587.1	None
mRNA	AJ243526.1	CAB76398.1
mRNA	AK313385.1	BAG36183.1
mRNA	AL136690.1	CAB66625.1
mRNA	BC014896.1	AAH14896.1
mRNA	BI752849.1	None
mRNA	BT006835.1	AAP35481.1
mRNA	BU584005.1	None
mRNA	CR457216.1	CAG33497.1
mRNA	CT841507.1	CAJ86437.1
other-genetic	AM393395.1	CAL38273.1
other-genetic	CU013072.1	CAK54503.1
other-genetic	CU013360.1	CAK54802.1