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 increa... See more...

Aliases for USP18 Gene

Aliases for USP18 Gene

  • Ubiquitin Specific Peptidase 18 2 3 5
  • Ubl Carboxyl-Terminal Hydrolase 18 2 3 4
  • ISG15-Specific-Processing Protease 3 4
  • Ubiquitin Specific Protease 18 2 3
  • 43 KDa ISG15-Specific Protease 3 4
  • Ubl Thioesterase 18 3 4
  • HUBP43 3 4
  • ISG43 3 4
  • Ubl Thiolesterase 18 3
  • EC 3.1.2.15 50
  • EC 3.4.19.- 4
  • PTORCH2 3
  • UBP43 3
  • USP18 5

External Ids for USP18 Gene

Previous GeneCards Identifiers for USP18 Gene

  • GC22P015573
  • GC22P017007
  • GC22P018632
  • GC22P002445

Summaries for USP18 Gene

Entrez Gene Summary for USP18 Gene

  • 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]

GeneCards Summary for USP18 Gene

USP18 (Ubiquitin Specific Peptidase 18) is a Protein Coding gene. Diseases associated with USP18 include Pseudo-Torch Syndrome 2 and Torch Syndrome. Among its related pathways are Immune response IFN alpha/beta signaling pathway and Peginterferon alpha-2a/Peginterferon alpha-2b Pathway (Hepatocyte), Pharmacodynamics. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and thiol-dependent ubiquitinyl hydrolase activity. An important paralog of this gene is USP41.

UniProtKB/Swiss-Prot Summary for USP18 Gene

  • Involved in the regulation of inflammatory response to interferon type 1 (PubMed:27325888). Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms.
  • [Isoform 2]: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (PubMed:22170061).

Gene Wiki entry for USP18 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP18 Gene

Genomics for USP18 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for USP18 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around USP18 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP18

Top Transcription factor binding sites by QIAGEN in the USP18 gene promoter:
  • HOXA5
  • HTF
  • Pax-2
  • Pax-2a
  • Pax-2b
  • POU2F1
  • POU2F1a
  • STAT1
  • STAT1alpha
  • STAT1beta

Genomic Locations for USP18 Gene

Latest Assembly
chr22:18,149,855-18,177,397
(GRCh38/hg38)
Size:
27,543 bases
Orientation:
Plus strand

Previous Assembly
chr22:18,632,937-18,660,164
(GRCh37/hg19 by Entrez Gene)
Size:
27,228 bases
Orientation:
Plus strand

chr22:18,632,666-18,660,164
(GRCh37/hg19 by Ensembl)
Size:
27,499 bases
Orientation:
Plus strand

Genomic View for USP18 Gene

Genes around USP18 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP18 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP18 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP18 Gene

Proteins for USP18 Gene

  • Protein details for USP18 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UMW8-UBP18_HUMAN
    Recommended name:
    Ubl carboxyl-terminal hydrolase 18
    Protein Accession:
    Q9UMW8
    Secondary Accessions:
    • Q53Y90
    • Q6IAD9
    • Q9NY71

    Protein attributes for USP18 Gene

    Size:
    372 amino acids
    Molecular mass:
    43011 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • [Isoform 2]: Produced by alternative initiation at a CTG start codon. An IRES Element in the 5' region contributes to expression.

    Alternative splice isoforms for USP18 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP18 Gene

Selected DME Specific Peptides for USP18 Gene

Q9UMW8:
  • VDGKWFCFNDS
  • LLLLEKMQDSRQKA
  • ILKRITVPR

Post-translational modifications for USP18 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for USP18 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for USP18
  • Boster Bio Antibodies for USP18
  • Santa Cruz Biotechnology (SCBT) Antibodies for USP18

Domains & Families for USP18 Gene

Gene Families for USP18 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for USP18 Gene

InterPro:
Blocks:
  • Ubiquitin thiolesterase, family 2

Suggested Antigen Peptide Sequences for USP18 Gene

GenScript: Design optimal peptide antigens:
  • Ubl thiolesterase 18 (UBP18_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UMW8

UniProtKB/Swiss-Prot:

UBP18_HUMAN :
  • Belongs to the peptidase C19 family.
Family:
  • Belongs to the peptidase C19 family.
genes like me logo Genes that share domains with USP18: view

Function for USP18 Gene

Molecular function for USP18 Gene

UniProtKB/Swiss-Prot Function:
Involved in the regulation of inflammatory response to interferon type 1 (PubMed:27325888). Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (PubMed:22170061).
GENATLAS Biochemistry:
ubiquitin specific protease 18,deubiquitin enzyme family

Enzyme Numbers (IUBMB) for USP18 Gene

Phenotypes From GWAS Catalog for USP18 Gene

Gene Ontology (GO) - Molecular Function for USP18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity IBA 21873635
GO:0004843 thiol-dependent ubiquitin-specific protease activity TAS,IBA 21873635
GO:0005515 protein binding IPI 16189514
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with USP18: view
genes like me logo Genes that share phenotypes with USP18: view

Human Phenotype Ontology for USP18 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for USP18 Gene

MGI Knock Outs for USP18:

miRNA for USP18 Gene

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP18

No data available for Transcription Factor Targets and HOMER Transcription for USP18 Gene

Localization for USP18 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP18 Gene

[Isoform 1]: Cytoplasm.
[Isoform 2]: Nucleus. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for USP18 gene
Compartment Confidence
cytosol 5
nucleus 4
extracellular 3
plasma membrane 2
mitochondrion 2
endosome 2
lysosome 2
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for USP18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0043231 intracellular membrane-bounded organelle IDA --
genes like me logo Genes that share ontologies with USP18: view

Pathways & Interactions for USP18 Gene

genes like me logo Genes that share pathways with USP18: view

Pathways by source for USP18 Gene

1 GeneGo (Thomson Reuters) pathway for USP18 Gene
  • Immune response IFN alpha/beta signaling pathway
1 Qiagen pathway for USP18 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis

Gene Ontology (GO) - Biological Process for USP18 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0016579 protein deubiquitination IBA,TAS --
GO:0018215 protein phosphopantetheinylation IEA --
GO:0050727 regulation of inflammatory response IMP 27325888
genes like me logo Genes that share ontologies with USP18: view

No data available for SIGNOR curated interactions for USP18 Gene

Drugs & Compounds for USP18 Gene

No Compound Related Data Available

Transcripts for USP18 Gene

mRNA/cDNA for USP18 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP18

Alternative Splicing Database (ASD) splice patterns (SP) for USP18 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11
SP1: -
SP2:
SP3:

Relevant External Links for USP18 Gene

GeneLoc Exon Structure for
USP18

Expression for USP18 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for USP18 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for USP18 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for USP18

SOURCE GeneReport for Unigene cluster for USP18 Gene:

Hs.38260

Evidence on tissue expression from TISSUES for USP18 Gene

  • Nervous system(4.5)
  • Liver(2.7)
  • Spleen(2.4)
  • Lymph node(2.2)
  • Blood(2.2)
genes like me logo Genes that share expression patterns with USP18: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP18 Gene

Orthologs for USP18 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for USP18 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia USP18 29 30
  • 99.01 (n)
OneToMany
Dog
(Canis familiaris)
Mammalia USP18 29
  • 84.68 (n)
-- 30
  • 80 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia USP18 29 30
  • 81.3 (n)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Usp18 29
  • 78.8 (n)
Mouse
(Mus musculus)
Mammalia Usp18 29 16 30
  • 77.69 (n)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 63 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 60 (a)
OneToMany
Chicken
(Gallus gallus)
Aves USP18 29
  • 60.84 (n)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia usp18 29
  • 50.49 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC100334535 29
  • 46.03 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Ubp64E 30
  • 6 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea T05H10.1 30
  • 7 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP15 30
  • 6 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 7 (a)
OneToMany
Species where no ortholog for USP18 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for USP18 Gene

ENSEMBL:
Gene Tree for USP18 (if available)
TreeFam:
Gene Tree for USP18 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for USP18: view image
Alliance of Genome Resources:
Additional Orthologs for USP18

Paralogs for USP18 Gene

Variants for USP18 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP18 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
997607 Pathogenic: Pseudo-TORCH syndrome 2 18,170,869(+) T/TCA
NM_017414.4(USP18):c.840_841insCA (p.Phe281fs)
FRAMESHIFT
rs1085307118 Pathogenic: Pseudo-TORCH syndrome 2 18,169,868(+) C/T
NM_017414.4(USP18):c.652C>T (p.Gln218Ter)
NONSENSE
rs115275255 Likely Benign: not provided 18,157,760(+) G/A
NM_017414.4(USP18):c.97G>A (p.Asp33Asn)
MISSENSE
rs1261330328 Likely Benign: not provided 18,170,827(+) G/A
NM_017414.4(USP18):c.798G>A (p.Thr266=)
SYNONYMOUS
rs138144879 Likely Benign: not provided 18,160,233(+) C/T
NM_017414.4(USP18):c.219C>T (p.Phe73=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for USP18 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for USP18 Gene

Variant ID Type Subtype PubMed ID
dgv1283e212 CNV gain 25503493
dgv173e55 CNV gain 17911159
dgv4466n100 CNV gain+loss 25217958
dgv4467n100 CNV gain 25217958
dgv99e203 CNV gain+loss 21179565
esv22247 CNV gain+loss 19812545
esv2751935 CNV loss 17911159
esv2758824 CNV gain+loss 17122850
esv32687 CNV gain+loss 17666407
esv3331783 CNV duplication 20981092
esv3575418 CNV gain 25503493
esv3893430 CNV gain 25118596
nsv1055756 CNV gain 25217958
nsv1058565 CNV gain 25217958
nsv1061694 CNV gain 25217958
nsv428385 CNV gain+loss 18775914
nsv469560 CNV gain 16826518
nsv471339 CNV gain 19718026
nsv471594 CNV gain+loss 15918152
nsv514961 CNV gain 21397061
nsv516997 CNV gain+loss 19592680
nsv962754 CNV duplication 23825009

Variation tolerance for USP18 Gene

Residual Variation Intolerance Score: 54.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.67; 31.85% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for USP18 Gene

Human Gene Mutation Database (HGMD)
USP18
SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP18
Leiden Open Variation Database (LOVD)
USP18

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP18 Gene

Disorders for USP18 Gene

MalaCards: The human disease database

(6) MalaCards diseases for USP18 Gene - From: OMI, CVR, GTR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search USP18 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

UBP18_HUMAN
  • Pseudo-TORCH syndrome 2 (PTORCH2) [MIM:617397]: An autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. {ECO:0000269 PubMed:27325888}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for USP18

genes like me logo Genes that share disorders with USP18: view

No data available for Genatlas for USP18 Gene

Publications for USP18 Gene

  1. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. (PMID: 27325888) Meuwissen ME … Mancini GM (The Journal of experimental medicine 2016) 3 4 72
  2. Cloning and characterization of a novel human ubiquitin-specific protease, a homologue of murine UBP43 (Usp18). (PMID: 10777664) Schwer H … Zhang DE (Genomics 2000) 3 4 22
  3. Two independent mechanisms promote expression of an N-terminal truncated USP18 isoform with higher DeISGylation activity in the nucleus. (PMID: 22170061) Burkart C … Zhang DE (The Journal of biological chemistry 2012) 3 4
  4. A genome annotation-driven approach to cloning the human ORFeome. (PMID: 15461802) Collins JE … Dunham I (Genome biology 2004) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for USP18 Gene

Sources for USP18 Gene