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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei64 – 641NucleophilePROSITE-ProRule annotation
Active sitei318 – 3181Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.
REACT_25216. 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
ProteomesiUP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:12616. USP18.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37242.

Polymorphism and mutation databases

BioMutaiUSP18.
DMDMi10720335.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 372372Ubl carboxyl-terminal hydrolase 18PRO_0000080644Add
BLAST

Proteomic databases

MaxQBiQ9UMW8.
PaxDbiQ9UMW8.
PRIDEiQ9UMW8.

PTM databases

PhosphoSiteiQ9UMW8.

Expressioni

Gene expression databases

BgeeiQ9UMW8.
CleanExiHS_USP18.
GenevisibleiQ9UMW8. HS.

Organism-specific databases

HPAiHPA044768.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
IFNAR2P485514EBI-356206,EBI-958408
ISG15P051614EBI-356206,EBI-746466

Protein-protein interaction databases

BioGridi116430. 13 interactions.
IntActiQ9UMW8. 21 interactions.
MINTiMINT-1134944.
STRINGi9606.ENSP00000215794.

Structurei

3D structure databases

ProteinModelPortaliQ9UMW8.
SMRiQ9UMW8. Positions 53-371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini55 – 370316USPAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000294166.
HOVERGENiHBG054189.
InParanoidiQ9UMW8.
KOiK11846.
OMAiYCAYIRS.
OrthoDBiEOG7VHSXG.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti332 – 3321F → S in CAB76398 (PubMed:10777664).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti169 – 1691T → M.1 Publication
Corresponds to variant rs3180408 [ dbSNP | Ensembl ].
VAR_024589

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1616MSKAF…CQSIL → M in isoform 2. CuratedVSP_055236Add
BLAST

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.
GeneIDi11274.
KEGGihsa:11274.
UCSCiuc002zny.3. 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.
SMRiQ9UMW8. Positions 53-371.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116430. 13 interactions.
IntActiQ9UMW8. 21 interactions.
MINTiMINT-1134944.
STRINGi9606.ENSP00000215794.

Protein family/group databases

MEROPSiC19.030.

PTM databases

PhosphoSiteiQ9UMW8.

Polymorphism and mutation databases

BioMutaiUSP18.
DMDMi10720335.

Proteomic databases

MaxQBiQ9UMW8.
PaxDbiQ9UMW8.
PRIDEiQ9UMW8.

Protocols and materials databases

DNASUi11274.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215794; ENSP00000215794; ENSG00000184979.
GeneIDi11274.
KEGGihsa:11274.
UCSCiuc002zny.3. human. [Q9UMW8-1]

Organism-specific databases

CTDi11274.
GeneCardsiGC22P018632.
H-InvDBHIX0041132.
HGNCiHGNC:12616. USP18.
HPAiHPA044768.
MIMi607057. gene.
neXtProtiNX_Q9UMW8.
PharmGKBiPA37242.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000294166.
HOVERGENiHBG054189.
InParanoidiQ9UMW8.
KOiK11846.
OMAiYCAYIRS.
OrthoDBiEOG7VHSXG.
PhylomeDBiQ9UMW8.

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.
REACT_25216. Regulation of IFNA signaling.

Miscellaneous databases

GeneWikiiUSP18.
GenomeRNAii11274.
NextBioi42911.
PROiQ9UMW8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UMW8.
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...

Publicationsi

« Hide 'large scale' publications
  1. "RNase-L-dependent regulation of a novel interferon-stimulated gene: feedback inhibition of the interferon response."
    Li X.-L., Blackford J.A., Judge C.S., Liu M., Xiao W., Kalvakolanu D.V., Hassel B.A.
    Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Cloning and characterization of a novel human ubiquitin-specific protease, a homologue of murine UBP43 (Usp18)."
    Schwer H., Liu L.Q., Zhou L., Little M.T., Pan Z., Hetherington C.J.
    Genomics 65:44-52(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Ovary.
  7. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-169.
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Uterus.
  9. "UBP43 (USP18) specifically removes ISG15 from conjugated proteins."
    Malakhov M.P., Malakhova O.A., Kim K.I., Ritchie K.J., Zhang D.-E.
    J. Biol. Chem. 277:9976-9981(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  10. "Two independent mechanisms promote expression of an N-terminal truncated USP18 isoform with higher DeISGylation activity in the nucleus."
    Burkart C., Fan J.B., Zhang D.E.
    J. Biol. Chem. 287:4883-4893(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE INITIATION (ISOFORM 2), CTG START CODON (ISOFORM 2), FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION.

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: July 22, 2015
This is version 137 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

External Data

Dasty 3

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 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.