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Q9UMW8

- UBP18_HUMAN

UniProt

Q9UMW8 - UBP18_HUMAN

Protein

Ubl carboxyl-terminal hydrolase 18

Gene

USP18

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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

    1. protein binding Source: IntAct
    2. ubiquitin-specific protease activity Source: ProtInc

    GO - Biological processi

    1. cytokine-mediated signaling pathway Source: Reactome
    2. regulation of type I interferon-mediated signaling pathway Source: Reactome
    3. type I interferon signaling pathway Source: Reactome
    4. ubiquitin-dependent protein catabolic process Source: InterPro

    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: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:12616. USP18.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: LIFEdb

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA37242.

    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

    ArrayExpressiQ9UMW8.
    BgeeiQ9UMW8.
    CleanExiHS_USP18.
    GenevestigatoriQ9UMW8.

    Organism-specific databases

    HPAiHPA044768.

    Interactioni

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi116430. 10 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.
    HOGENOMiHOG000294166.
    HOVERGENiHBG054189.
    InParanoidiQ9UMW8.
    KOiK11846.
    OMAiIRNSVDG.
    OrthoDBiEOG7VHSXG.
    PhylomeDBiQ9UMW8.

    Family and domain databases

    InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [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. Align

    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

    MSKAFGLLRQ ICQSILAESS QSPADLEEKK EEDSNMKREQ PRERPRAWDY    50
    PHGLVGLHNI GQTCCLNSLI QVFVMNVDFT RILKRITVPR GADEQRRSVP 100
    FQMLLLLEKM QDSRQKAVRP LELAYCLQKC NVPLFVQHDA AQLYLKLWNL 150
    IKDQITDVHL VERLQALYTI RVKDSLICVD CAMESSRNSS MLTLPLSLFD 200
    VDSKPLKTLE DALHCFFQPR ELSSKSKCFC ENCGKKTRGK QVLKLTHLPQ 250
    TLTIHLMRFS IRNSQTRKIC HSLYFPQSLD FSQILPMKRE SCDAEEQSGG 300
    QYELFAVIAH VGMADSGHYC VYIRNAVDGK WFCFNDSNIC LVSWEDIQCT 350
    YGNPNYHWQE TAYLLVYMKM EC 372
    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:
    EMBL
    GenBank
    DDBJ
    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.
    UniGeneiHs.38260.

    Genome annotation databases

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

    Polymorphism databases

    DMDMi10720335.

    Keywords - Coding sequence diversityi

    Alternative initiation, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS13752.1. [Q9UMW8-1 ]
    RefSeqi NP_059110.2. NM_017414.3.
    UniGenei Hs.38260.

    3D structure databases

    ProteinModelPortali Q9UMW8.
    SMRi Q9UMW8. Positions 53-371.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116430. 10 interactions.
    IntActi Q9UMW8. 21 interactions.
    MINTi MINT-1134944.
    STRINGi 9606.ENSP00000215794.

    Protein family/group databases

    MEROPSi C19.030.

    PTM databases

    PhosphoSitei Q9UMW8.

    Polymorphism databases

    DMDMi 10720335.

    Proteomic databases

    MaxQBi Q9UMW8.
    PaxDbi Q9UMW8.
    PRIDEi Q9UMW8.

    Protocols and materials databases

    DNASUi 11274.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000215794 ; ENSP00000215794 ; ENSG00000184979 . [Q9UMW8-1 ]
    GeneIDi 11274.
    KEGGi hsa:11274.
    UCSCi uc002zny.3. human. [Q9UMW8-1 ]

    Organism-specific databases

    CTDi 11274.
    GeneCardsi GC22P018632.
    H-InvDB HIX0041132.
    HGNCi HGNC:12616. USP18.
    HPAi HPA044768.
    MIMi 607057. gene.
    neXtProti NX_Q9UMW8.
    PharmGKBi PA37242.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5077.
    HOGENOMi HOG000294166.
    HOVERGENi HBG054189.
    InParanoidi Q9UMW8.
    KOi K11846.
    OMAi IRNSVDG.
    OrthoDBi EOG7VHSXG.
    PhylomeDBi Q9UMW8.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.
    REACT_25216. Regulation of IFNA signaling.

    Miscellaneous databases

    GeneWikii USP18.
    GenomeRNAii 11274.
    NextBioi 42911.
    PROi Q9UMW8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UMW8.
    Bgeei Q9UMW8.
    CleanExi HS_USP18.
    Genevestigatori Q9UMW8.

    Family and domain databases

    InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [Graphical view ]
    Pfami PF00443. UCH. 1 hit.
    [Graphical view ]
    PROSITEi PS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 128 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