Q9UMW8 (UBP18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	USP18
Synonyms:	ISG43

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	372 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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).
Sequence similarities	Belongs to the peptidase C19 family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: LIFEdb
Molecular_function	ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 372	372	Ubl carboxyl-terminal hydrolase 18		PRO_0000080644
Sites
	Active site	64	1	Nucleophile By similarity
	Active site	318	1	Proton acceptor By similarity
Natural variations
	Natural variant	169	1	T → M. Ref.4 Corresponds to variant rs3180408 [ dbSNP | Ensembl ].		VAR_024589
Experimental info
	Sequence conflict	332	1	F → S in CAB76398. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UMW8 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 60248E8D4CC42BF0	FASTA	372	43,011
	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

References

	« Hide 'large scale' referencesShow '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].
[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].
[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. , 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]. Tissue: Brain.
[4]	"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], VARIANT MET-169.
[5]	"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]. Tissue: Uterus.
[6]	"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.
+	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. CR457216 mRNA. Translation: CAG33497.1. BC014896 mRNA. Translation: AAH14896.1.
IPI	IPI00183040.
RefSeq	NP_059110.2. NM_017414.3.
UniGene	Hs.38260.
3D structure databases
ProteinModelPortal	Q9UMW8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UMW8. 5 interactions.
MINT	MINT-1134944.
STRING	9606.ENSP00000215794.
Protein family/group databases
MEROPS	C19.030.
PTM databases
PhosphoSite	Q9UMW8.
Polymorphism databases
DMDM	10720335.
Proteomic databases
PaxDb	Q9UMW8.
PRIDE	Q9UMW8.
Protocols and materials databases
DNASU	11274.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000215794; ENSP00000215794; ENSG00000184979.
GeneID	11274.
KEGG	hsa:11274.
UCSC	uc002zny.3. human.
Organism-specific databases
CTD	11274.
GeneCards	GC22P018632.
H-InvDB	HIX0041132.
HGNC	HGNC:12616. USP18.
HPA	HPA044768.
MIM	607057. gene.
neXtProt	NX_Q9UMW8.
PharmGKB	PA37242.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5077.
HOGENOM	HOG000294166.
HOVERGEN	HBG054189.
InParanoid	Q9UMW8.
KO	K11846.
OMA	LYLTVWN.
OrthoDB	EOG4C2HBB.
PhylomeDB	Q9UMW8.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9UMW8.
Bgee	Q9UMW8.
CleanEx	HS_USP18.
Genevestigator	Q9UMW8.
GermOnline	ENSG00000184979. Homo sapiens.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF00443. UCH. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	11274.
NextBio	42911.
SOURCE	Search...

Entry information

Entry name

UBP18_HUMAN

Accession

Primary (citable) accession number: Q9UMW8
Secondary accession number(s): Q6IAD9, Q9NY71

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.