Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9UMW8 (UBP18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP18
Synonyms:ISG43
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length372 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10

Isoform 2:Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (Ref.10). Ref.10

Catalytic activity

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).

Subcellular location

Isoform 1: Cytoplasm Ref.10.

Isoform 2: Nucleus Ref.10.

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 USP domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IFNAR2P485514EBI-356206,EBI-958408

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: Q9UMW8-1)

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.
Isoform 2 (identifier: Q9UMW8-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 372372Ubl carboxyl-terminal hydrolase 18
PRO_0000080644

Regions

Domain55 – 370316USP

Sites

Active site641Nucleophile By similarity
Active site3181Proton acceptor By similarity

Natural variations

Alternative sequence1 – 1616MSKAF…CQSIL → M in isoform 2.
VSP_055236
Natural variant1691T → M. Ref.7
Corresponds to variant rs3180408 [ dbSNP | Ensembl ].
VAR_024589

Experimental info

Sequence conflict3321F → S in CAB76398. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 60248E8D4CC42BF0

FASTA37243,011
        10         20         30         40         50         60 
MSKAFGLLRQ ICQSILAESS QSPADLEEKK EEDSNMKREQ PRERPRAWDY PHGLVGLHNI 

        70         80         90        100        110        120 
GQTCCLNSLI QVFVMNVDFT RILKRITVPR GADEQRRSVP FQMLLLLEKM QDSRQKAVRP 

       130        140        150        160        170        180 
LELAYCLQKC NVPLFVQHDA AQLYLKLWNL IKDQITDVHL VERLQALYTI RVKDSLICVD 

       190        200        210        220        230        240 
CAMESSRNSS MLTLPLSLFD VDSKPLKTLE DALHCFFQPR ELSSKSKCFC ENCGKKTRGK 

       250        260        270        280        290        300 
QVLKLTHLPQ TLTIHLMRFS IRNSQTRKIC HSLYFPQSLD FSQILPMKRE SCDAEEQSGG 

       310        320        330        340        350        360 
QYELFAVIAH VGMADSGHYC VYIRNAVDGK WFCFNDSNIC LVSWEDIQCT YGNPNYHWQE 

       370 
TAYLLVYMKM EC 

« Hide

Isoform 2 (USP18-sf) [UniParc].

Checksum: 18E94FFF540F905F
Show »

FASTA35741,352

References

« Hide 'large scale' references
[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]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
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]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13752.1.
RefSeqNP_059110.2. NM_017414.3.
UniGeneHs.38260.

3D structure databases

ProteinModelPortalQ9UMW8.
SMRQ9UMW8. Positions 53-371.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116430. 9 interactions.
IntActQ9UMW8. 8 interactions.
MINTMINT-1134944.
STRING9606.ENSP00000215794.

Protein family/group databases

MEROPSC19.030.

PTM databases

PhosphoSiteQ9UMW8.

Polymorphism databases

DMDM10720335.

Proteomic databases

MaxQBQ9UMW8.
PaxDbQ9UMW8.
PRIDEQ9UMW8.

Protocols and materials databases

DNASU11274.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000215794; ENSP00000215794; ENSG00000184979.
GeneID11274.
KEGGhsa:11274.
UCSCuc002zny.3. human.

Organism-specific databases

CTD11274.
GeneCardsGC22P018632.
H-InvDBHIX0041132.
HGNCHGNC:12616. USP18.
HPAHPA044768.
MIM607057. gene.
neXtProtNX_Q9UMW8.
PharmGKBPA37242.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000294166.
HOVERGENHBG054189.
InParanoidQ9UMW8.
KOK11846.
OMAIRNSVDG.
OrthoDBEOG7VHSXG.
PhylomeDBQ9UMW8.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9UMW8.
BgeeQ9UMW8.
CleanExHS_USP18.
GenevestigatorQ9UMW8.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUSP18.
GenomeRNAi11274.
NextBio42911.
PROQ9UMW8.
SOURCESearch...

Entry information

Entry nameUBP18_HUMAN
AccessionPrimary (citable) accession number: Q9UMW8
Secondary accession number(s): Q53Y90, Q6IAD9, Q9NY71
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM