UBP18_MOUSE
ID UBP18_MOUSE Reviewed; 368 AA.
AC Q9WTV6; Q3U7P3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Ubl carboxyl-terminal hydrolase 18;
DE EC=3.4.19.-;
DE AltName: Full=43 kDa ISG15-specific protease;
DE AltName: Full=ISG15-specific-processing protease;
DE AltName: Full=Ubl thioesterase 18;
GN Name=Usp18; Synonyms=Ubp43;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymus;
RX PubMed=10082570; DOI=10.1128/mcb.19.4.3029;
RA Liu L., Ilaria R. Jr., Kingsley P.D., Iwama A., van Etten R.A., Palis J.,
RA Zhang D.-E.;
RT "A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion
RT protein AML1-ETO-expressing mice, functions in hematopoietic cell
RT differentiation.";
RL Mol. Cell. Biol. 19:3029-3038(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
CC -!- FUNCTION: Involved in the negative regulation of the inflammatory
CC response triggered by type I interferon. Upon recruitment by STAT2 to
CC the type I IFN receptor subunit IFNAR2 interferes with the assembly of
CC the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative
CC regulator of the type I IFN signaling pathway. Also regulates protein
CC ISGylation. Can efficiently cleave only ISG15 fusions including native
CC ISG15 conjugates linked via isopeptide bonds. Necessary to maintain a
CC critical cellular balance of ISG15-conjugated proteins in both healthy
CC and stressed organisms. {ECO:0000250|UniProtKB:Q9UMW8}.
CC -!- SUBUNIT: Interacts with STAT2; the interaction is direct. Interacts
CC with IFNAR2; indirectly via STAT2, it negatively regulates the assembly
CC of the ternary interferon-IFNAR1-IFNAR2 complex and inhibits type I
CC interferon signaling. {ECO:0000250|UniProtKB:Q9UMW8}.
CC -!- INTERACTION:
CC Q9WTV6; Q64339: Isg15; NbExp=4; IntAct=EBI-9119995, EBI-8345781;
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AF069502; AAD21222.1; -; mRNA.
DR EMBL; AK152034; BAE30893.1; -; mRNA.
DR EMBL; AK152574; BAE31326.1; -; mRNA.
DR EMBL; AK153312; BAE31893.1; -; mRNA.
DR CCDS; CCDS20489.1; -.
DR RefSeq; NP_036039.2; NM_011909.2.
DR PDB; 5CHT; X-ray; 2.80 A; A/B=46-368.
DR PDB; 5CHV; X-ray; 3.00 A; A/B=46-368.
DR PDBsum; 5CHT; -.
DR PDBsum; 5CHV; -.
DR AlphaFoldDB; Q9WTV6; -.
DR SMR; Q9WTV6; -.
DR BioGRID; 204902; 5.
DR IntAct; Q9WTV6; 1.
DR MINT; Q9WTV6; -.
DR STRING; 10090.ENSMUSP00000032198; -.
DR MEROPS; C19.030; -.
DR PhosphoSitePlus; Q9WTV6; -.
DR MaxQB; Q9WTV6; -.
DR PaxDb; Q9WTV6; -.
DR PRIDE; Q9WTV6; -.
DR ProteomicsDB; 298096; -.
DR DNASU; 24110; -.
DR Ensembl; ENSMUST00000032198; ENSMUSP00000032198; ENSMUSG00000030107.
DR GeneID; 24110; -.
DR KEGG; mmu:24110; -.
DR UCSC; uc009dog.2; mouse.
DR CTD; 11274; -.
DR MGI; MGI:1344364; Usp18.
DR VEuPathDB; HostDB:ENSMUSG00000030107; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000161720; -.
DR HOGENOM; CLU_062837_0_0_1; -.
DR InParanoid; Q9WTV6; -.
DR OMA; CAYIRNS; -.
DR OrthoDB; 147564at2759; -.
DR PhylomeDB; Q9WTV6; -.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR BioGRID-ORCS; 24110; 18 hits in 74 CRISPR screens.
DR ChiTaRS; Usp18; mouse.
DR PRO; PR:Q9WTV6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9WTV6; protein.
DR Bgee; ENSMUSG00000030107; Expressed in small intestine Peyer's patch and 124 other tissues.
DR ExpressionAtlas; Q9WTV6; baseline and differential.
DR Genevisible; Q9WTV6; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0019785; F:ISG15-specific peptidase activity; IMP:MGI.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0035634; P:response to stilbenoid; IEP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
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 Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation pathway.
FT CHAIN 1..368
FT /note="Ubl carboxyl-terminal hydrolase 18"
FT /id="PRO_0000080645"
FT DOMAIN 52..366
FT /note="USP"
FT /evidence="ECO:0000255"
FT REGION 31..48
FT /note="Mediates interaction with IFNAR2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMW8"
FT REGION 48..109
FT /note="Mediates interaction with STAT2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMW8"
FT REGION 299..308
FT /note="Mediates interaction with STAT2 and necessary for
FT the negative regulation of the type I IFN signaling
FT pathway"
FT /evidence="ECO:0000250|UniProtKB:Q9UMW8"
FT REGION 309..368
FT /note="Mediates interaction with IFNAR2"
FT /evidence="ECO:0000250|UniProtKB:Q9UMW8"
FT ACT_SITE 61
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 314
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT CONFLICT 115
FT /note="V -> L (in Ref. 1; AAD21222)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="S -> T (in Ref. 1; AAD21222)"
FT /evidence="ECO:0000305"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 74..81
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 96..109
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 131..135
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 137..151
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 167..178
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 183..193
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 206..213
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:5CHT"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 235..243
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 246..252
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:5CHV"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:5CHV"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 298..309
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 312..320
FT /evidence="ECO:0007829|PDB:5CHT"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:5CHT"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5CHT"
FT STRAND 357..365
FT /evidence="ECO:0007829|PDB:5CHT"
SQ SEQUENCE 368 AA; 42472 MW; 19A4458FEB44CC22 CRC64;
MGKGFGLLRK PCQSVVAEPQ QYSALEEERT MKRKRVLSRD LCSAWDSPHG LVGLHNIGQT
CCLNSLLQVF MMNMDFRMIL KRITVPRSAE ERKRSVPFQL LLLLEKMQDS RQKAVLPTEL
VQCLQKYNVP LFVQHDAAQL YLTIWNLTKD QITDTDLTER LQGLFTIWTQ ESLICVGCTA
ESSRRSKLLT LSLPLFDKDA KPLKTLEDAL RCFVQPKELA SSDMCCESCG EKTPWKQVLK
LTHLPQTLTI HLMRFSARNS RTEKICHSVN FPQSLDFSQV LPTEEDLGDT KEQSEIHYEL
FAVIAHVGMA DFGHYCAYIR NPVDGKWFCF NDSHVCWVTW KDVQCTYGNH RYRWRETAYL
LVYTKTGS
