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Protein

Ubl carboxyl-terminal hydrolase 18

Gene

USP18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).1 Publication

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei64NucleophilePROSITE-ProRule annotation1
Active sitei318Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • ISG15-specific protease activity Source: Reactome
  • thiol-dependent ubiquitin-specific protease activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-912694. Regulation of IFNA signaling.

Protein family/group databases

MEROPSiC19.030.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubl carboxyl-terminal hydrolase 18 (EC:3.4.19.-)
Alternative name(s):
43 kDa ISG15-specific protease
Short name:
hUBP43
ISG15-specific-processing protease
Ubl thioesterase 18
Gene namesi
Name:USP18
Synonyms:ISG43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:12616. USP18.

Subcellular locationi

Isoform 1 :
  • Cytoplasm 1 Publication
Isoform 2 :
  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi11274.
OpenTargetsiENSG00000184979.
PharmGKBiPA37242.

Chemistry databases

ChEMBLiCHEMBL3407317.

Polymorphism and mutation databases

BioMutaiUSP18.
DMDMi10720335.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806441 – 372Ubl carboxyl-terminal hydrolase 18Add BLAST372

Proteomic databases

PaxDbiQ9UMW8.
PeptideAtlasiQ9UMW8.
PRIDEiQ9UMW8.

PTM databases

iPTMnetiQ9UMW8.
PhosphoSitePlusiQ9UMW8.

Expressioni

Gene expression databases

BgeeiENSG00000184979.
CleanExiHS_USP18.
GenevisibleiQ9UMW8. HS.

Organism-specific databases

HPAiHPA044768.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
IFNAR2P485514EBI-356206,EBI-958408
ISG15P051618EBI-356206,EBI-746466

Protein-protein interaction databases

BioGridi116430. 25 interactors.
DIPiDIP-42723N.
IntActiQ9UMW8. 21 interactors.
MINTiMINT-1134944.
STRINGi9606.ENSP00000215794.

Chemistry databases

BindingDBiQ9UMW8.

Structurei

3D structure databases

ProteinModelPortaliQ9UMW8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 370USPAdd BLAST316

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000294166.
HOVERGENiHBG054189.
InParanoidiQ9UMW8.
KOiK11846.
OMAiYCAYIRS.
OrthoDBiEOG091G0NHS.
PhylomeDBiQ9UMW8.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q9UMW8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSKAFGLLRQ ICQSILAESS QSPADLEEKK EEDSNMKREQ PRERPRAWDY
60 70 80 90 100
PHGLVGLHNI GQTCCLNSLI QVFVMNVDFT RILKRITVPR GADEQRRSVP
110 120 130 140 150
FQMLLLLEKM QDSRQKAVRP LELAYCLQKC NVPLFVQHDA AQLYLKLWNL
160 170 180 190 200
IKDQITDVHL VERLQALYTI RVKDSLICVD CAMESSRNSS MLTLPLSLFD
210 220 230 240 250
VDSKPLKTLE DALHCFFQPR ELSSKSKCFC ENCGKKTRGK QVLKLTHLPQ
260 270 280 290 300
TLTIHLMRFS IRNSQTRKIC HSLYFPQSLD FSQILPMKRE SCDAEEQSGG
310 320 330 340 350
QYELFAVIAH VGMADSGHYC VYIRNAVDGK WFCFNDSNIC LVSWEDIQCT
360 370
YGNPNYHWQE TAYLLVYMKM EC
Length:372
Mass (Da):43,011
Last modified:May 1, 2000 - v1
Checksum:i60248E8D4CC42BF0
GO
Isoform 2 (identifier: Q9UMW8-2) [UniParc]FASTAAdd to basket
Also known as: USP18-sf

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MSKAFGLLRQICQSIL → M

Note: Produced by alternative initiation at a CTG start codon. An IRES Element in the 5' region contributes to expression.
Show »
Length:357
Mass (Da):41,352
Checksum:i18E94FFF540F905F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti332F → S in CAB76398 (PubMed:10777664).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024589169T → M.1 PublicationCorresponds to variant rs3180408dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0552361 – 16MSKAF…CQSIL → M in isoform 2. CuratedAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176642 mRNA. Translation: AAD49967.1.
AJ243526 mRNA. Translation: CAB76398.1.
AL136690 mRNA. Translation: CAB66625.1.
BT006835 mRNA. Translation: AAP35481.1.
CT841507 mRNA. Translation: CAJ86437.1.
AK313385 mRNA. Translation: BAG36183.1.
CR457216 mRNA. Translation: CAG33497.1.
BC014896 mRNA. Translation: AAH14896.1.
CCDSiCCDS13752.1. [Q9UMW8-1]
RefSeqiNP_059110.2. NM_017414.3. [Q9UMW8-1]
UniGeneiHs.38260.

Genome annotation databases

EnsembliENST00000215794; ENSP00000215794; ENSG00000184979. [Q9UMW8-1]
GeneIDi11274.
KEGGihsa:11274.
UCSCiuc002zny.4. human. [Q9UMW8-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176642 mRNA. Translation: AAD49967.1.
AJ243526 mRNA. Translation: CAB76398.1.
AL136690 mRNA. Translation: CAB66625.1.
BT006835 mRNA. Translation: AAP35481.1.
CT841507 mRNA. Translation: CAJ86437.1.
AK313385 mRNA. Translation: BAG36183.1.
CR457216 mRNA. Translation: CAG33497.1.
BC014896 mRNA. Translation: AAH14896.1.
CCDSiCCDS13752.1. [Q9UMW8-1]
RefSeqiNP_059110.2. NM_017414.3. [Q9UMW8-1]
UniGeneiHs.38260.

3D structure databases

ProteinModelPortaliQ9UMW8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116430. 25 interactors.
DIPiDIP-42723N.
IntActiQ9UMW8. 21 interactors.
MINTiMINT-1134944.
STRINGi9606.ENSP00000215794.

Chemistry databases

BindingDBiQ9UMW8.
ChEMBLiCHEMBL3407317.

Protein family/group databases

MEROPSiC19.030.

PTM databases

iPTMnetiQ9UMW8.
PhosphoSitePlusiQ9UMW8.

Polymorphism and mutation databases

BioMutaiUSP18.
DMDMi10720335.

Proteomic databases

PaxDbiQ9UMW8.
PeptideAtlasiQ9UMW8.
PRIDEiQ9UMW8.

Protocols and materials databases

DNASUi11274.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215794; ENSP00000215794; ENSG00000184979. [Q9UMW8-1]
GeneIDi11274.
KEGGihsa:11274.
UCSCiuc002zny.4. human. [Q9UMW8-1]

Organism-specific databases

CTDi11274.
DisGeNETi11274.
GeneCardsiUSP18.
H-InvDBHIX0041132.
HGNCiHGNC:12616. USP18.
HPAiHPA044768.
MIMi607057. gene.
neXtProtiNX_Q9UMW8.
OpenTargetsiENSG00000184979.
PharmGKBiPA37242.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000294166.
HOVERGENiHBG054189.
InParanoidiQ9UMW8.
KOiK11846.
OMAiYCAYIRS.
OrthoDBiEOG091G0NHS.
PhylomeDBiQ9UMW8.

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-912694. Regulation of IFNA signaling.

Miscellaneous databases

GeneWikiiUSP18.
GenomeRNAii11274.
PROiQ9UMW8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184979.
CleanExiHS_USP18.
GenevisibleiQ9UMW8. HS.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP18_HUMAN
AccessioniPrimary (citable) accession number: Q9UMW8
Secondary accession number(s): Q53Y90, Q6IAD9, Q9NY71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.