ID   UBP18_HUMAN             Reviewed;         372 AA.
AC   Q9UMW8; Q53Y90; Q6IAD9; Q9NY71;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 195.
DE   RecName: Full=Ubl carboxyl-terminal hydrolase 18;
DE            EC=3.4.19.12 {ECO:0000269|PubMed:23825189};
DE   AltName: Full=43 kDa ISG15-specific protease;
DE            Short=hUBP43;
DE   AltName: Full=ISG15-specific-processing protease;
DE   AltName: Full=Ubl thioesterase 18;
GN   Name=USP18; Synonyms=ISG43;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Li X.-L., Blackford J.A., Judge C.S., Liu M., Xiao W., Kalvakolanu D.V.,
RA   Hassel B.A.;
RT   "RNase-L-dependent regulation of a novel interferon-stimulated gene:
RT   feedback inhibition of the interferon response.";
RL   Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=10777664; DOI=10.1006/geno.2000.6148;
RA   Schwer H., Liu L.Q., Zhou L., Little M.T., Pan Z., Hetherington C.J.;
RT   "Cloning and characterization of a novel human ubiquitin-specific protease,
RT   a homologue of murine UBP43 (Usp18).";
RL   Genomics 65:44-52(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Ovary;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-169.
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Uterus;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   INDUCTION BY TYPE I INTERFERON.
RX   PubMed=11313150; DOI=10.1016/s0378-1119(01)00384-5;
RA   Kang D., Jiang H., Wu Q., Pestka S., Fisher P.B.;
RT   "Cloning and characterization of human ubiquitin-processing protease-43
RT   from terminally differentiated human melanoma cells using a rapid
RT   subtraction hybridization protocol RaSH.";
RL   Gene 267:233-242(2001).
RN   [10]
RP   FUNCTION.
RX   PubMed=11788588; DOI=10.1074/jbc.m109078200;
RA   Malakhov M.P., Malakhova O.A., Kim K.I., Ritchie K.J., Zhang D.-E.;
RT   "UBP43 (USP18) specifically removes ISG15 from conjugated proteins.";
RL   J. Biol. Chem. 277:9976-9981(2002).
RN   [11]
RP   ALTERNATIVE INITIATION (ISOFORM 2), CTG START CODON (ISOFORM 2), FUNCTION
RP   (ISOFORM 2), AND SUBCELLULAR LOCATION.
RX   PubMed=22170061; DOI=10.1074/jbc.m111.255570;
RA   Burkart C., Fan J.B., Zhang D.E.;
RT   "Two independent mechanisms promote expression of an N-terminal truncated
RT   USP18 isoform with higher DeISGylation activity in the nucleus.";
RL   J. Biol. Chem. 287:4883-4893(2012).
RN   [12]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-64.
RX   PubMed=23825189; DOI=10.1084/jem.20122327;
RA   Liu X., Li H., Zhong B., Blonska M., Gorjestani S., Yan M., Tian Q.,
RA   Zhang D.E., Lin X., Dong C.;
RT   "USP18 inhibits NF-kappaB and NFAT activation during Th17 differentiation
RT   by deubiquitinating the TAK1-TAB1 complex.";
RL   J. Exp. Med. 210:1575-1590(2013).
RN   [13]
RP   FUNCTION, INVOLVEMENT IN PTORCH2, AND VARIANT PTORCH2 218-GLN--CYS-372 DEL.
RX   PubMed=27325888; DOI=10.1084/jem.20151529;
RA   Meuwissen M.E., Schot R., Buta S., Oudesluijs G., Tinschert S., Speer S.D.,
RA   Li Z., van Unen L., Heijsman D., Goldmann T., Lequin M.H., Kros J.M.,
RA   Stam W., Hermann M., Willemsen R., Brouwer R.W., Van Ijcken W.F.,
RA   Martin-Fernandez M., de Coo I., Dudink J., de Vries F.A.,
RA   Bertoli Avella A., Prinz M., Crow Y.J., Verheijen F.W., Pellegrini S.,
RA   Bogunovic D., Mancini G.M.;
RT   "Human USP18 deficiency underlies type 1 interferonopathy leading to severe
RT   pseudo-TORCH syndrome.";
RL   J. Exp. Med. 213:1163-1174(2016).
RN   [14]
RP   FUNCTION, AND INTERACTION WITH USP20 AND STING1.
RX   PubMed=27801882; DOI=10.1038/cr.2016.125;
RA   Zhang M., Zhang M.X., Zhang Q., Zhu G.F., Yuan L., Zhang D.E., Zhu Q.,
RA   Yao J., Shu H.B., Zhong B.;
RT   "USP18 recruits USP20 to promote innate antiviral response through
RT   deubiquitinating STING/MITA.";
RL   Cell Res. 26:1302-1319(2016).
RN   [15]
RP   FUNCTION, INTERACTION WITH IFNAR2 AND STAT2, AND REGION.
RX   PubMed=28165510; DOI=10.1038/nsmb.3378;
RA   Arimoto K.I., Loechte S., Stoner S.A., Burkart C., Zhang Y., Miyauchi S.,
RA   Wilmes S., Fan J.B., Heinisch J.J., Li Z., Yan M., Pellegrini S.,
RA   Colland F., Piehler J., Zhang D.E.;
RT   "STAT2 is an essential adaptor in USP18-mediated suppression of type I
RT   interferon signaling.";
RL   Nat. Struct. Mol. Biol. 24:279-289(2017).
RN   [16]
RP   INTERACTION WITH STAT2.
RX   PubMed=31836668; DOI=10.1126/sciimmunol.aav7501;
RA   Duncan C.J.A., Thompson B.J., Chen R., Rice G.I., Gothe F., Young D.F.,
RA   Lovell S.C., Shuttleworth V.G., Brocklebank V., Corner B., Skelton A.J.,
RA   Bondet V., Coxhead J., Duffy D., Fourrage C., Livingston J.H., Pavaine J.,
RA   Cheesman E., Bitetti S., Grainger A., Acres M., Innes B.A., Mikulasova A.,
RA   Sun R., Hussain R., Wright R., Wynn R., Zarhrate M., Zeef L.A.H., Wood K.,
RA   Hughes S.M., Harris C.L., Engelhardt K.R., Crow Y.J., Randall R.E.,
RA   Kavanagh D., Hambleton S., Briggs T.A.;
RT   "Severe type I interferonopathy and unrestrained interferon signaling due
RT   to a homozygous germline mutation in STAT2.";
RL   Sci. Immunol. 4:0-0(2019).
RN   [17]
RP   INTERACTION WITH STAT2.
RX   PubMed=32092142; DOI=10.1084/jem.20192319;
RA   Gruber C., Martin-Fernandez M., Ailal F., Qiu X., Taft J., Altman J.,
RA   Rosain J., Buta S., Bousfiha A., Casanova J.L., Bustamante J.,
RA   Bogunovic D.;
RT   "Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a
RT   patient with type I interferonopathy.";
RL   J. Exp. Med. 217:0-0(2020).
CC   -!- FUNCTION: Interferon-induced ISG15-specific protease that plays a
CC       crucial role for maintaining a proper balance of ISG15-conjugated
CC       proteins in cells (PubMed:11788588). Regulates protein ISGylation by
CC       efficiently cleaving ISG15 conjugates linked via isopeptide bonds.
CC       Regulates T-cell activation and T-helper 17 (Th17) cell differentiation
CC       by deubiquitinating TAK1, likely to keep TAK1-TAB complexes in steady
CC       conditions (PubMed:23825189). In turn, restricts activation of NF-
CC       kappa-B, NFAT, and JNK as well as expression of IL2 in T-cells after
CC       TCR activation (PubMed:23825189). Acts as a molecular adapter with
CC       USP20 to promote innate antiviral response through deubiquitinating
CC       STING1 (PubMed:27801882). Involved also in the negative regulation of
CC       the inflammatory response triggered by type I interferon
CC       (PubMed:28165510, PubMed:27325888). Upon recruitment by STAT2 to the
CC       type I interferon receptor subunit IFNAR2 interferes with the assembly
CC       of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative
CC       regulator of the type I interferon signaling pathway (PubMed:28165510).
CC       {ECO:0000269|PubMed:11788588, ECO:0000269|PubMed:23825189,
CC       ECO:0000269|PubMed:27325888, ECO:0000269|PubMed:27801882,
CC       ECO:0000269|PubMed:28165510}.
CC   -!- FUNCTION: [Isoform 2]: Has enzymatic activity similar to isoform 1 and
CC       interferes with type I interferon signaling. Major deISGylation enzyme
CC       for nuclear proteins (PubMed:22170061). {ECO:0000269|PubMed:22170061}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:27801882};
CC   -!- SUBUNIT: Interacts with STAT2; the interaction is direct
CC       (PubMed:28165510, PubMed:31836668, PubMed:32092142). Interacts with
CC       IFNAR2; indirectly via STAT2, it negatively regulates the assembly of
CC       the ternary interferon-IFNAR1-IFNAR2 complex and inhibits type I
CC       interferon signaling (PubMed:28165510). Interacts with STING1.
CC       Interacts with USP20. {ECO:0000269|PubMed:28165510,
CC       ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142}.
CC   -!- INTERACTION:
CC       Q9UMW8; P42858: HTT; NbExp=3; IntAct=EBI-356206, EBI-466029;
CC       Q9UMW8; P48551: IFNAR2; NbExp=4; IntAct=EBI-356206, EBI-958408;
CC       Q9UMW8; P05161: ISG15; NbExp=9; IntAct=EBI-356206, EBI-746466;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC       {ECO:0000269|PubMed:22170061}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC       {ECO:0000269|PubMed:22170061}. Cytoplasm {ECO:0000269|PubMed:22170061}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9UMW8-1; Sequence=Displayed;
CC       Name=2; Synonyms=USP18-sf;
CC         IsoId=Q9UMW8-2; Sequence=VSP_055236;
CC   -!- INDUCTION: By type I interferon, predominantly IFN-beta.
CC       {ECO:0000269|PubMed:11313150}.
CC   -!- DISEASE: Pseudo-TORCH syndrome 2 (PTORCH2) [MIM:617397]: An autosomal
CC       recessive multisystem disorder characterized by antenatal onset of
CC       intracranial hemorrhage, calcification, brain malformations, liver
CC       dysfunction, and often thrombocytopenia. Affected individuals tend to
CC       have respiratory insufficiency and seizures, and die in infancy. The
CC       phenotype resembles the sequelae of intrauterine infection, but there
CC       is no evidence of an infectious agent. {ECO:0000269|PubMed:27325888}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at a CTG
CC       start codon. An IRES Element in the 5' region contributes to
CC       expression. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AF176642; AAD49967.1; -; mRNA.
DR   EMBL; AJ243526; CAB76398.1; -; mRNA.
DR   EMBL; AL136690; CAB66625.1; -; mRNA.
DR   EMBL; BT006835; AAP35481.1; -; mRNA.
DR   EMBL; CT841507; CAJ86437.1; -; mRNA.
DR   EMBL; AK313385; BAG36183.1; -; mRNA.
DR   EMBL; CR457216; CAG33497.1; -; mRNA.
DR   EMBL; BC014896; AAH14896.1; -; mRNA.
DR   CCDS; CCDS13752.1; -. [Q9UMW8-1]
DR   RefSeq; NP_059110.2; NM_017414.3. [Q9UMW8-1]
DR   AlphaFoldDB; Q9UMW8; -.
DR   SMR; Q9UMW8; -.
DR   BioGRID; 116430; 51.
DR   DIP; DIP-42723N; -.
DR   IntAct; Q9UMW8; 23.
DR   MINT; Q9UMW8; -.
DR   STRING; 9606.ENSP00000215794; -.
DR   BindingDB; Q9UMW8; -.
DR   ChEMBL; CHEMBL3407317; -.
DR   MEROPS; C19.030; -.
DR   iPTMnet; Q9UMW8; -.
DR   PhosphoSitePlus; Q9UMW8; -.
DR   BioMuta; USP18; -.
DR   DMDM; 10720335; -.
DR   jPOST; Q9UMW8; -.
DR   MassIVE; Q9UMW8; -.
DR   MaxQB; Q9UMW8; -.
DR   PaxDb; 9606-ENSP00000215794; -.
DR   PeptideAtlas; Q9UMW8; -.
DR   ProteomicsDB; 85214; -. [Q9UMW8-1]
DR   Antibodypedia; 22768; 138 antibodies from 32 providers.
DR   CPTC; Q9UMW8; 1 antibody.
DR   DNASU; 11274; -.
DR   Ensembl; ENST00000215794.8; ENSP00000215794.7; ENSG00000184979.11. [Q9UMW8-1]
DR   GeneID; 11274; -.
DR   KEGG; hsa:11274; -.
DR   MANE-Select; ENST00000215794.8; ENSP00000215794.7; NM_017414.4; NP_059110.2.
DR   UCSC; uc002zny.4; human. [Q9UMW8-1]
DR   AGR; HGNC:12616; -.
DR   CTD; 11274; -.
DR   DisGeNET; 11274; -.
DR   GeneCards; USP18; -.
DR   HGNC; HGNC:12616; USP18.
DR   HPA; ENSG00000184979; Low tissue specificity.
DR   MalaCards; USP18; -.
DR   MIM; 607057; gene.
DR   MIM; 617397; phenotype.
DR   neXtProt; NX_Q9UMW8; -.
DR   OpenTargets; ENSG00000184979; -.
DR   Orphanet; 481665; USP18 deficiency.
DR   PharmGKB; PA37242; -.
DR   VEuPathDB; HostDB:ENSG00000184979; -.
DR   eggNOG; KOG1863; Eukaryota.
DR   GeneTree; ENSGT00940000161720; -.
DR   HOGENOM; CLU_062837_0_0_1; -.
DR   InParanoid; Q9UMW8; -.
DR   OMA; CAYIRNS; -.
DR   OrthoDB; 24284at2759; -.
DR   PhylomeDB; Q9UMW8; -.
DR   PathwayCommons; Q9UMW8; -.
DR   Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR   Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR   Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR   Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling.
DR   Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling.
DR   SignaLink; Q9UMW8; -.
DR   BioGRID-ORCS; 11274; 92 hits in 1196 CRISPR screens.
DR   GeneWiki; USP18; -.
DR   GenomeRNAi; 11274; -.
DR   Pharos; Q9UMW8; Tbio.
DR   PRO; PR:Q9UMW8; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q9UMW8; Protein.
DR   Bgee; ENSG00000184979; Expressed in primordial germ cell in gonad and 106 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IC:UniProt.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:LIFEdb.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR   GO; GO:0019785; F:ISG15-specific peptidase activity; EXP:Reactome.
DR   GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt.
DR   GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt.
DR   GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR   GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR   GO; GO:0035634; P:response to stilbenoid; IEA:Ensembl.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF796; UBL CARBOXYL-TERMINAL HYDROLASE 18-RELATED; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; Q9UMW8; HS.
PE   1: Evidence at protein level;
KW   Alternative initiation; Cytoplasm; Hydrolase; Nucleus; Protease;
KW   Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..372
FT                   /note="Ubl carboxyl-terminal hydrolase 18"
FT                   /id="PRO_0000080644"
FT   DOMAIN          55..370
FT                   /note="USP"
FT                   /evidence="ECO:0000255"
FT   REGION          19..45
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          36..51
FT                   /note="Mediates interaction with IFNAR2"
FT                   /evidence="ECO:0000269|PubMed:28165510"
FT   REGION          51..112
FT                   /note="Mediates interaction with STAT2"
FT                   /evidence="ECO:0000269|PubMed:28165510"
FT   REGION          303..312
FT                   /note="Mediates interaction with STAT2 and necessary for
FT                   the negative regulation of the type I IFN signaling
FT                   pathway"
FT                   /evidence="ECO:0000269|PubMed:28165510"
FT   REGION          313..372
FT                   /note="Mediates interaction with IFNAR2"
FT                   /evidence="ECO:0000269|PubMed:28165510"
FT   COMPBIAS        23..45
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        64
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        318
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   VAR_SEQ         1..16
FT                   /note="MSKAFGLLRQICQSIL -> M (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_055236"
FT   VARIANT         169
FT                   /note="T -> M (in dbSNP:rs3180408)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_024589"
FT   VARIANT         218..372
FT                   /note="Missing (in PTORCH2)"
FT                   /evidence="ECO:0000269|PubMed:27325888"
FT                   /id="VAR_078772"
FT   MUTAGEN         64
FT                   /note="C->S: Abolishes deubiquitinating activity."
FT                   /evidence="ECO:0000269|PubMed:23825189"
FT   CONFLICT        332
FT                   /note="F -> S (in Ref. 2; CAB76398)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   372 AA;  43011 MW;  60248E8D4CC42BF0 CRC64;
     MSKAFGLLRQ ICQSILAESS QSPADLEEKK EEDSNMKREQ PRERPRAWDY PHGLVGLHNI
     GQTCCLNSLI QVFVMNVDFT RILKRITVPR GADEQRRSVP FQMLLLLEKM QDSRQKAVRP
     LELAYCLQKC NVPLFVQHDA AQLYLKLWNL IKDQITDVHL VERLQALYTI RVKDSLICVD
     CAMESSRNSS MLTLPLSLFD VDSKPLKTLE DALHCFFQPR ELSSKSKCFC ENCGKKTRGK
     QVLKLTHLPQ TLTIHLMRFS IRNSQTRKIC HSLYFPQSLD FSQILPMKRE SCDAEEQSGG
     QYELFAVIAH VGMADSGHYC VYIRNAVDGK WFCFNDSNIC LVSWEDIQCT YGNPNYHWQE
     TAYLLVYMKM EC
//