ISG15_HUMAN
ID ISG15_HUMAN Reviewed; 165 AA.
AC P05161; Q5SVA4; Q7Z2G2; Q96GF0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Ubiquitin-like protein ISG15;
DE AltName: Full=Interferon-induced 15 kDa protein;
DE AltName: Full=Interferon-induced 17 kDa protein;
DE Short=IP17;
DE AltName: Full=Ubiquitin cross-reactive protein;
DE Short=hUCRP;
DE Flags: Precursor;
GN Name=ISG15 {ECO:0000312|HGNC:HGNC:4053}; Synonyms=G1P2, UCRP;
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].
RX PubMed=3087979; DOI=10.1016/s0021-9258(19)84453-8;
RA Blomstrom D.C., Fahey D., Kutny R., Korant B.D., Knight E. Jr.;
RT "Molecular characterization of the interferon-induced 15-kDa protein.
RT Molecular cloning and nucleotide and amino acid sequence.";
RL J. Biol. Chem. 261:8811-8816(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3476954; DOI=10.1073/pnas.84.18.6394;
RA Reich N., Evans B., Levy D., Fahey D., Knight E. Jr., Darnell J.E. Jr.;
RT "Interferon-induced transcription of a gene encoding a 15-kDa protein
RT depends on an upstream enhancer element.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6394-6398(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEOLYTIC PROCESSING.
RX PubMed=3350799; DOI=10.1016/s0021-9258(18)68812-x;
RA Knight E. Jr., Fahey D., Cordova B., Hillman M. Jr., Kutny R., Reich N.,
RA Blomstrom D.C.;
RT "A 15-kDa interferon-induced protein is derived by COOH-terminal processing
RT of a 17-kDa precursor.";
RL J. Biol. Chem. 263:4520-4522(1988).
RN [4]
RP ERRATUM OF PUBMED:3350799.
RA Knight E. Jr., Fahey D., Cordova B., Hillman M. Jr., Kutny R., Reich N.,
RA Blomstrom D.C.;
RL J. Biol. Chem. 263:10040-10040(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-83.
RC TISSUE=Testis;
RA Kamitani T., Fukuda-Kamitani T.;
RT "Conjugation by ubiquitin-like proteins.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-83.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-83.
RC TISSUE=Colon;
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 [10]
RP PROTEIN SEQUENCE OF 2-38 AND 151-165, AND PROTEOLYTIC PROCESSING.
RX PubMed=2477469; DOI=10.1089/jir.1989.9.493;
RA Feltham N., Hillman M. Jr., Cordova B., Fahey D., Larsen B.,
RA Blomstrom D.C., Knight E. Jr.;
RT "A 15-kD interferon-induced protein and its 17-kD precursor: expression in
RT Escherichia coli, purification, and characterization.";
RL J. Interferon Res. 9:493-507(1989).
RN [11]
RP SIMILARITY TO UBIQUITIN.
RX PubMed=2440890; DOI=10.1016/s0021-9258(18)60961-5;
RA Haas A.L., Ahrens P., Bright P.M., Ankel H.;
RT "Interferon induces a 15-kilodalton protein exhibiting marked homology to
RT ubiquitin.";
RL J. Biol. Chem. 262:11315-11323(1987).
RN [12]
RP FUNCTION.
RX PubMed=1373138; DOI=10.1016/s0021-9258(18)42585-9;
RA Loeb K.R., Haas A.L.;
RT "The interferon-inducible 15-kDa ubiquitin homolog conjugates to
RT intracellular proteins.";
RL J. Biol. Chem. 267:7806-7813(1992).
RN [13]
RP FUNCTION.
RX PubMed=7526157; DOI=10.1128/mcb.14.12.8408-8419.1994;
RA Loeb K.R., Haas A.L.;
RT "Conjugates of ubiquitin cross-reactive protein distribute in a
RT cytoskeletal pattern.";
RL Mol. Cell. Biol. 14:8408-8419(1994).
RN [14]
RP FUNCTION.
RX PubMed=8550581; DOI=10.1074/jbc.271.1.324;
RA Narasimhan J., Potter J.L., Haas A.L.;
RT "Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct
RT from that of ubiquitin.";
RL J. Biol. Chem. 271:324-330(1996).
RN [15]
RP FUNCTION.
RX PubMed=2005397;
RA Knight E. Jr., Cordova B.;
RT "IFN-induced 15-kDa protein is released from human lymphocytes and
RT monocytes.";
RL J. Immunol. 146:2280-2284(1991).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=7490683; DOI=10.1002/path.1711770210;
RA Lowe J., McDermott H., Loeb K., Landon M., Haas A.L., Mayer R.J.;
RT "Immunohistochemical localization of ubiquitin cross-reactive protein in
RT human tissues.";
RL J. Pathol. 177:163-169(1995).
RN [17]
RP INTERACTION WITH UBE1L AND INFLUENZA B NS1.
RX PubMed=11157743; DOI=10.1093/emboj/20.3.362;
RA Yuan W., Krug R.M.;
RT "Influenza B virus NS1 protein inhibits conjugation of the interferon
RT (IFN)-induced ubiquitin-like ISG15 protein.";
RL EMBO J. 20:362-371(2001).
RN [18]
RP CHARACTERIZATION.
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 [19]
RP INTERACTION WITH UBE2E2.
RX PubMed=15131269; DOI=10.1073/pnas.0402528101;
RA Zhao C., Beaudenon S.L., Kelley M.L., Waddell M.B., Yuan W., Schulman B.A.,
RA Huibregtse J.M., Krug R.M.;
RT "The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-
RT alpha/beta-induced ubiquitin-like protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7578-7582(2004).
RN [20]
RP FUNCTION IN UBE2N ISGYLATION.
RX PubMed=16112642; DOI=10.1016/j.bbrc.2005.08.034;
RA Takeuchi T., Yokosawa H.;
RT "ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating
RT activity.";
RL Biochem. Biophys. Res. Commun. 336:9-13(2005).
RN [21]
RP FUNCTION IN UBE2E1 AND UBE2L6 ISGYLATION.
RX PubMed=16428300; DOI=10.1093/jb/mvi172;
RA Takeuchi T., Iwahara S., Saeki Y., Sasajima H., Yokosawa H.;
RT "Link between the ubiquitin conjugation system and the ISG15 conjugation
RT system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme.";
RL J. Biochem. 138:711-719(2005).
RN [22]
RP FUNCTION IN IFIT1; DDX58 AND MX1 ISGYLATION.
RX PubMed=16009940; DOI=10.1073/pnas.0504754102;
RA Zhao C., Denison C., Huibregtse J.M., Gygi S.P., Krug R.M.;
RT "Human ISG15 conjugation targets both IFN-induced and constitutively
RT expressed proteins functioning in diverse cellular pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10200-10205(2005).
RN [23]
RP FUNCTION IN PPM1B ISGYLATION.
RX PubMed=16872604; DOI=10.1016/j.febslet.2006.07.032;
RA Takeuchi T., Kobayashi T., Tamura S., Yokosawa H.;
RT "Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation.";
RL FEBS Lett. 580:4521-4526(2006).
RN [24]
RP FUNCTION IN HIV-1 RESTRICTION.
RX PubMed=16434471; DOI=10.1073/pnas.0510518103;
RA Okumura A., Lu G., Pitha-Rowe I., Pitha P.M.;
RT "Innate antiviral response targets HIV-1 release by the induction of
RT ubiquitin-like protein ISG15.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1440-1445(2006).
RN [25]
RP DOMAINS UBIQUITIN-LIKE 1 AND 2.
RX PubMed=18356159; DOI=10.1074/jbc.m800162200;
RA Chang Y.G., Yan X.Z., Xie Y.Y., Gao X.C., Song A.X., Zhang D.E., Hu H.Y.;
RT "Different roles for two ubiquitin-like domains of ISG15 in protein
RT modification.";
RL J. Biol. Chem. 283:13370-13377(2008).
RN [26]
RP S-NITROSYLATION AT CYS-78.
RX PubMed=18606809; DOI=10.1074/jbc.m803795200;
RA Okumura F., Lenschow D.J., Zhang D.E.;
RT "Nitrosylation of ISG15 prevents the disulfide bond-mediated dimerization
RT of ISG15 and contributes to effective ISGylation.";
RL J. Biol. Chem. 283:24484-24488(2008).
RN [27]
RP FUNCTION IN EBOLA VIRUS RESTRICTION, AND INTERACTION WITH NEDD4.
RX PubMed=18305167; DOI=10.1073/pnas.0710629105;
RA Okumura A., Pitha P.M., Harty R.N.;
RT "ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by
RT blocking Nedd4 ligase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3974-3979(2008).
RN [28]
RP FUNCTION IN FLNB ISGYLATION.
RX PubMed=19270716; DOI=10.1038/embor.2009.23;
RA Jeon Y.J., Choi J.S., Lee J.Y., Yu K.R., Kim S.M., Ka S.H., Oh K.H.,
RA Kim K.I., Zhang D.E., Bang O.S., Chung C.H.;
RT "ISG15 modification of filamin B negatively regulates the type I
RT interferon-induced JNK signalling pathway.";
RL EMBO Rep. 10:374-380(2009).
RN [29]
RP REVIEW.
RX PubMed=19680460; DOI=10.1159/000226245;
RA Harty R.N., Pitha P.M., Okumura A.;
RT "Antiviral activity of innate immune protein ISG15.";
RL J. Innate Immun. 1:397-404(2009).
RN [30]
RP FUNCTION IN INFLUENZA A VIRUS RESTRICTION.
RX PubMed=19357168; DOI=10.1128/jvi.01667-08;
RA Hsiang T.Y., Zhao C., Krug R.M.;
RT "Interferon-induced ISG15 conjugation inhibits influenza A virus gene
RT expression and replication in human cells.";
RL J. Virol. 83:5971-5977(2009).
RN [31]
RP REVIEW.
RX PubMed=20153823; DOI=10.1016/j.bbadis.2010.02.006;
RA Jeon Y.J., Yoo H.M., Chung C.H.;
RT "ISG15 and immune diseases.";
RL Biochim. Biophys. Acta 1802:485-496(2010).
RN [32]
RP REVIEW.
RX PubMed=20946978; DOI=10.1016/j.cell.2010.09.033;
RA Skaug B., Chen Z.J.;
RT "Emerging role of ISG15 in antiviral immunity.";
RL Cell 143:187-190(2010).
RN [33]
RP FUNCTION.
RX PubMed=20639253; DOI=10.1136/gut.2009.195545;
RA Broering R., Zhang X., Kottilil S., Trippler M., Jiang M., Lu M.,
RA Gerken G., Schlaak J.F.;
RT "The interferon stimulated gene 15 functions as a proviral factor for the
RT hepatitis C virus and as a regulator of the IFN response.";
RL Gut 59:1111-1119(2010).
RN [34]
RP FUNCTION IN IRF3 ISGYLATION.
RX PubMed=20308324; DOI=10.1128/mcb.01466-09;
RA Shi H.X., Yang K., Liu X., Liu X.Y., Wei B., Shan Y.F., Zhu L.H., Wang C.;
RT "Positive regulation of interferon regulatory factor 3 activation by Herc5
RT via ISG15 modification.";
RL Mol. Cell. Biol. 30:2424-2436(2010).
RN [35]
RP FUNCTION IN INFLUENZA A VIRUS NS1 ISGYLATION.
RX PubMed=20133869; DOI=10.1073/pnas.0909144107;
RA Zhao C., Hsiang T.Y., Kuo R.L., Krug R.M.;
RT "ISG15 conjugation system targets the viral NS1 protein in influenza A
RT virus-infected cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2253-2258(2010).
RN [36]
RP REVIEW.
RX PubMed=21994614; DOI=10.3390/v2102154;
RA Lenschow D.J.;
RT "Antiviral properties of ISG15.";
RL Viruses 2:2154-2168(2010).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [38]
RP REVIEW.
RX PubMed=21190487; DOI=10.1089/jir.2010.0110;
RA Zhang D., Zhang D.E.;
RT "Interferon-stimulated gene 15 and the protein ISGylation system.";
RL J. Interferon Cytokine Res. 31:119-130(2011).
RN [39]
RP FUNCTION IN CHMP5; CHMP2A; CHMP4B AND CHMP6 ISGYLATION.
RX PubMed=21543490; DOI=10.1128/jvi.02610-10;
RA Kuang Z., Seo E.J., Leis J.;
RT "Mechanism of inhibition of retrovirus release from cells by interferon-
RT induced gene ISG15.";
RL J. Virol. 85:7153-7161(2011).
RN [40]
RP INTERACTION WITH CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS RNA-DIRECTED RNA
RP POLYMERASE L (MICROBIAL INFECTION).
RX PubMed=21266548; DOI=10.1073/pnas.1015287108;
RA Akutsu M., Ye Y., Virdee S., Chin J.W., Komander D.;
RT "Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian
RT tumor domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2228-2233(2011).
RN [41]
RP INTERACTION WITH CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS RNA-DIRECTED RNA
RP POLYMERASE L (MICROBIAL INFECTION).
RX PubMed=21245344; DOI=10.1073/pnas.1013388108;
RA James T.W., Frias-Staheli N., Bacik J.P., Levingston Macleod J.M.,
RA Khajehpour M., Garcia-Sastre A., Mark B.L.;
RT "Structural basis for the removal of ubiquitin and interferon-stimulated
RT gene 15 by a viral ovarian tumor domain-containing protease.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2222-2227(2011).
RN [42]
RP REVIEW.
RX PubMed=22666250; DOI=10.1155/2012/532723;
RA Seo E.J., Leis J.;
RT "Budding of enveloped viruses: interferon-induced ISG15-antivirus
RT mechanisms targeting the release process.";
RL Adv. Virol. 2012:532723-532723(2012).
RN [43]
RP REVIEW.
RX PubMed=22906767; DOI=10.1016/j.cytogfr.2012.07.003;
RA Sgorbissa A., Brancolini C.;
RT "IFNs, ISGylation and cancer: Cui prodest?";
RL Cytokine Growth Factor Rev. 23:307-314(2012).
RN [44]
RP FUNCTION IN UBE2N AND UBA7 ISGYLATION, AND DISULFIDE BOND.
RX PubMed=22693631; DOI=10.1371/journal.pone.0038294;
RA Bade V.N., Nickels J., Keusekotten K., Praefcke G.J.;
RT "Covalent protein modification with ISG15 via a conserved cysteine in the
RT hinge region.";
RL PLoS ONE 7:E38294-E38294(2012).
RN [45]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP INVOLVEMENT IN IMD38.
RX PubMed=22859821; DOI=10.1126/science.1224026;
RA Bogunovic D., Byun M., Durfee L.A., Abhyankar A., Sanal O., Mansouri D.,
RA Salem S., Radovanovic I., Grant A.V., Adimi P., Mansouri N., Okada S.,
RA Bryant V.L., Kong X.F., Kreins A., Velez M.M., Boisson B., Khalilzadeh S.,
RA Ozcelik U., Darazam I.A., Schoggins J.W., Rice C.M., Al-Muhsen S., Behr M.,
RA Vogt G., Puel A., Bustamante J., Gros P., Huibregtse J.M., Abel L.,
RA Boisson-Dupuis S., Casanova J.L.;
RT "Mycobacterial disease and impaired IFN-gamma immunity in humans with
RT inherited ISG15 deficiency.";
RL Science 337:1684-1688(2012).
RN [46]
RP REVIEW.
RX PubMed=22964713; DOI=10.1038/cr.2012.133;
RA Fan J.B., Zhang D.E.;
RT "ISG15 regulates IFN-? immunity in human mycobacterial disease.";
RL Cell Res. 23:173-175(2013).
RN [47]
RP REVIEW.
RX PubMed=23579383; DOI=10.1038/emm.2013.36;
RA Bogunovic D., Boisson-Dupuis S., Casanova J.L.;
RT "ISG15: leading a double life as a secreted molecule.";
RL Exp. Mol. Med. 45:E18-E18(2013).
RN [48]
RP FUNCTION IN EIF2AK2 ISGYLATION.
RX PubMed=23229543; DOI=10.1074/jbc.m112.401851;
RA Okumura F., Okumura A.J., Uematsu K., Hatakeyama S., Zhang D.E., Kamura T.;
RT "Activation of double-stranded RNA-activated protein kinase (PKR) by
RT interferon-stimulated gene 15 (ISG15) modification down-regulates protein
RT translation.";
RL J. Biol. Chem. 288:2839-2847(2013).
RN [49]
RP REVIEW.
RX PubMed=23414970; DOI=10.1016/j.tim.2013.01.005;
RA Zhao C., Collins M.N., Hsiang T.Y., Krug R.M.;
RT "Interferon-induced ISG15 pathway: an ongoing virus-host battle.";
RL Trends Microbiol. 21:181-186(2013).
RN [50]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [51]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN E3.
RX PubMed=24257616; DOI=10.1128/jvi.03293-13;
RA Eduardo-Correia B., Martinez-Romero C., Garcia-Sastre A., Guerra S.;
RT "ISG15 is counteracted by vaccinia virus E3 protein and controls the
RT proinflammatory response against viral infection.";
RL J. Virol. 88:2312-2318(2014).
RN [52]
RP FUNCTION, AND MUTAGENESIS OF ARG-44; SER-83; TYR-96; ARG-99; THR-101;
RP GLN-102 AND THR-103.
RX PubMed=29100055; DOI=10.1016/j.molcel.2017.10.003;
RA Swaim C.D., Scott A.F., Canadeo L.A., Huibregtse J.M.;
RT "Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin
RT receptor.";
RL Mol. Cell 68:581-590(2017).
RN [53]
RP FUNCTION.
RX PubMed=33727702; DOI=10.1038/s41564-021-00884-1;
RA Liu G., Lee J.H., Parker Z.M., Acharya D., Chiang J.J., van Gent M.,
RA Riedl W., Davis-Gardner M.E., Wies E., Chiang C., Gack M.U.;
RT "ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-
RT CoV-2 papain-like protease to evade host innate immunity.";
RL Nat. Microbiol. 6:467-478(2021).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-155 OF MUTANT SER-78.
RX PubMed=15917233; DOI=10.1074/jbc.m502814200;
RA Narasimhan J., Wang M., Fu Z., Klein J.M., Haas A.L., Kim J.J.;
RT "Crystal structure of the interferon-induced ubiquitin-like protein
RT ISG15.";
RL J. Biol. Chem. 280:27356-27365(2005).
RN [55]
RP STRUCTURE BY NMR OF 79-157.
RG Northeast structural genomics consortium (NESG);
RT "Solution NMR structure of the C-terminal domain of the interferon alpha-
RT inducible ISG15 protein from Homo sapiens.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Ubiquitin-like protein which plays a key role in the innate
CC immune response to viral infection either via its conjugation to a
CC target protein (ISGylation) or via its action as a free or unconjugated
CC protein. ISGylation involves a cascade of enzymatic reactions involving
CC E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a
CC lysine residue in the target protein (PubMed:33727702). Its target
CC proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A,
CC CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes
CC IFIH1/MDA5 oligomerization and triggers activation of innate immunity
CC against a range of viruses, including coronaviruses, flaviviruses and
CC picornaviruses (PubMed:33727702). Can also isgylate: EIF2AK2/PKR which
CC results in its activation, DDX58/RIG-I which inhibits its function in
CC antiviral signaling response, EIF4E2 which enhances its cap structure-
CC binding activity and translation-inhibition activity, UBE2N and UBE2E1
CC which negatively regulates their activity, IRF3 which inhibits its
CC ubiquitination and degradation and FLNB which prevents its ability to
CC interact with the upstream activators of the JNK cascade thereby
CC inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity
CC towards both DNA and RNA viruses, including influenza A, HIV-1 and
CC Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral
CC budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and
CC disrupts their interaction, thereby preventing assembly and release of
CC virions from infected cells. Inhibits Ebola virus budding mediated by
CC the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and
CC its ability to ubiquitinate VP40. ISGylates influenza A virus NS1
CC protein which causes a loss of function of the protein and the
CC inhibition of virus replication. The secreted form of ISG15 can: induce
CC natural killer cell proliferation, act as a chemotactic factor for
CC neutrophils and act as a IFN-gamma-inducing cytokine playing an
CC essential role in antimycobacterial immunity. The secreted form acts
CC through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC
CC family tyrosine kinases including LYN, HCK and FGR which leads to
CC secretion of IFNG and IL10; the interaction is mediated by ITGAL
CC (PubMed:29100055). {ECO:0000269|PubMed:1373138,
CC ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642,
CC ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471,
CC ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167,
CC ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168,
CC ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869,
CC ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253,
CC ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631,
CC ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543,
CC ECO:0000269|PubMed:29100055, ECO:0000269|PubMed:33727702,
CC ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:2440890). Interacts with,
CC and is conjugated to its targets by UBE1L (E1 enzyme) and UBE2E2 (E2
CC enzyme) (PubMed:11157743, PubMed:15131269). Interacts with NEDD4
CC (PubMed:18305167). {ECO:0000269|PubMed:11157743,
CC ECO:0000269|PubMed:15131269, ECO:0000269|PubMed:18305167,
CC ECO:0000269|PubMed:2440890}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein
CC E3. {ECO:0000269|PubMed:24257616}.
CC -!- SUBUNIT: (Microbial infection) Interaction with influenza B NS1 protein
CC inhibits its conjugation. {ECO:0000269|PubMed:11157743}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with Crimean-
CC Congo hemorrhagic fever virus (CCHFV) RNA-directed RNA polymerase L
CC (via N-terminus); the deISGylase activity of the viral protein
CC interferes with antiviral signaling pathways mediated by NF-kappaB and
CC IRF signalings. {ECO:0000269|PubMed:21266548}.
CC -!- INTERACTION:
CC P05161; O75369: FLNB; NbExp=4; IntAct=EBI-746466, EBI-352089;
CC P05161; Q9BYX4: IFIH1; NbExp=7; IntAct=EBI-746466, EBI-6115771;
CC P05161; Q14653: IRF3; NbExp=2; IntAct=EBI-746466, EBI-2650369;
CC P05161; O75688: PPM1B; NbExp=2; IntAct=EBI-746466, EBI-1047039;
CC P05161; O60260-5: PRKN; NbExp=3; IntAct=EBI-746466, EBI-21251460;
CC P05161; P41226: UBA7; NbExp=10; IntAct=EBI-746466, EBI-751921;
CC P05161; Q9UMW8: USP18; NbExp=9; IntAct=EBI-746466, EBI-356206;
CC P05161; PRO_0000338257 [P0C6U8]: 1a; Xeno; NbExp=5; IntAct=EBI-746466, EBI-25635190;
CC P05161; Q6TQR6: L; Xeno; NbExp=5; IntAct=EBI-746466, EBI-4403908;
CC P05161; P03495: NS; Xeno; NbExp=4; IntAct=EBI-746466, EBI-2548993;
CC P05161; P03502: NS; Xeno; NbExp=4; IntAct=EBI-746466, EBI-15938710;
CC P05161; K0BWD0: orf1ab; Xeno; NbExp=4; IntAct=EBI-746466, EBI-25565992;
CC P05161; PRO_0000422441 [K9N7C7]: rep; Xeno; NbExp=4; IntAct=EBI-746466, EBI-25592237;
CC P05161; PRO_0000037311 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-746466, EBI-25474079;
CC P05161; PRO_0000449621 [P0DTD1]: rep; Xeno; NbExp=13; IntAct=EBI-746466, EBI-25492388;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22859821}. Secreted
CC {ECO:0000269|PubMed:22859821}. Note=Exists in three distinct states:
CC free within the cell, released into the extracellular space, or
CC conjugated to target proteins.
CC -!- TISSUE SPECIFICITY: Detected in lymphoid cells, striated and smooth
CC muscle, several epithelia and neurons. Expressed in neutrophils,
CC monocytes and lymphocytes. Enhanced expression seen in pancreatic
CC adenocarcinoma, endometrial cancer, and bladder cancer, as compared to
CC non-cancerous tissue. In bladder cancer, the increase in expression
CC exhibits a striking positive correlation with more advanced stages of
CC the disease. {ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:7490683}.
CC -!- INDUCTION: Strongly induced upon exposure to type I interferons,
CC viruses, LPS, and other stresses, including certain genotoxic stresses.
CC {ECO:0000269|PubMed:22859821}.
CC -!- DOMAIN: Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are
CC required for its efficient conjugation to cellular proteins. The two
CC domains play different roles in the ISGylation pathway: Ubiquitin-like
CC 2 domain is necessary for the first two steps allowing the linking of
CC ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is
CC essential for the final, E3-mediated transfer of ISG15, from the E2 to
CC the Lys of the target protein (PubMed:18356159).
CC {ECO:0000269|PubMed:18356159}.
CC -!- PTM: S-nitrosylation decreases its dimerization, thereby increasing the
CC availability as well as the solubility of monomeric ISG15 for its
CC conjugation to cellular proteins. {ECO:0000269|PubMed:18606809}.
CC -!- PTM: Induced as an inactive, precursor protein that is cleaved by
CC specific proteases to expose the C-terminal diglycine (LRLRGG) motif.
CC This motif is essential not only for its conjugation to substrates but
CC also for its recognition by the relevant processing proteases.
CC {ECO:0000269|PubMed:2477469, ECO:0000269|PubMed:3350799}.
CC -!- DISEASE: Immunodeficiency 38, with basal ganglia calcification (IMD38)
CC [MIM:616126]: A primary immunodeficiency predisposing individuals to
CC severe clinical disease upon infection with weakly virulent
CC mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin
CC (BCG) vaccines. Patients are also susceptible to Salmonella and
CC Mycobacterium tuberculosis infections. Affected individuals have
CC intracranial calcification. {ECO:0000269|PubMed:22859821}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=On guard - Issue 240 of
CC October 2021;
CC URL="https://web.expasy.org/spotlight/back_issues/234/";
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DR EMBL; M13755; AAA36038.1; -; mRNA.
DR EMBL; M21786; AAA36128.1; -; Genomic_DNA.
DR EMBL; AY168648; AAN86983.1; -; mRNA.
DR EMBL; BT007297; AAP35961.1; -; mRNA.
DR EMBL; AL645608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471183; EAW56295.1; -; Genomic_DNA.
DR EMBL; BC009507; AAH09507.1; -; mRNA.
DR CCDS; CCDS6.1; -.
DR PIR; A28304; A28138.
DR RefSeq; NP_005092.1; NM_005101.3.
DR PDB; 1Z2M; X-ray; 2.50 A; A=1-155.
DR PDB; 2HJ8; NMR; -; A=79-157.
DR PDB; 3PHX; X-ray; 1.60 A; B=79-156.
DR PDB; 3PSE; X-ray; 2.30 A; B=1-156.
DR PDB; 3R66; X-ray; 2.30 A; C/D=1-157.
DR PDB; 3RT3; X-ray; 2.01 A; B=1-158.
DR PDB; 3SDL; X-ray; 2.29 A; C/D=1-157.
DR PDB; 5TL6; X-ray; 2.62 A; A/C=80-157.
DR PDB; 5W8T; X-ray; 2.76 A; B/D=80-156.
DR PDB; 5W8U; X-ray; 2.41 A; B/D=80-156.
DR PDB; 6BI8; X-ray; 3.00 A; C/D=1-156.
DR PDB; 6FFA; X-ray; 1.50 A; B=79-155.
DR PDB; 6XA9; X-ray; 2.90 A; B/D/F=79-157.
DR PDB; 7RBS; X-ray; 2.98 A; B/D/F/H/J=2-157.
DR PDB; 7S6P; X-ray; 2.15 A; A/B/C/D/E/F=2-157.
DR PDBsum; 1Z2M; -.
DR PDBsum; 2HJ8; -.
DR PDBsum; 3PHX; -.
DR PDBsum; 3PSE; -.
DR PDBsum; 3R66; -.
DR PDBsum; 3RT3; -.
DR PDBsum; 3SDL; -.
DR PDBsum; 5TL6; -.
DR PDBsum; 5W8T; -.
DR PDBsum; 5W8U; -.
DR PDBsum; 6BI8; -.
DR PDBsum; 6FFA; -.
DR PDBsum; 6XA9; -.
DR PDBsum; 7RBS; -.
DR PDBsum; 7S6P; -.
DR AlphaFoldDB; P05161; -.
DR BMRB; P05161; -.
DR SMR; P05161; -.
DR BioGRID; 114995; 398.
DR DIP; DIP-29814N; -.
DR IntAct; P05161; 64.
DR MINT; P05161; -.
DR STRING; 9606.ENSP00000368699; -.
DR GlyGen; P05161; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P05161; -.
DR PhosphoSitePlus; P05161; -.
DR BioMuta; ISG15; -.
DR DMDM; 52001470; -.
DR EPD; P05161; -.
DR jPOST; P05161; -.
DR MassIVE; P05161; -.
DR MaxQB; P05161; -.
DR PaxDb; P05161; -.
DR PeptideAtlas; P05161; -.
DR PRIDE; P05161; -.
DR ProteomicsDB; 51809; -.
DR TopDownProteomics; P05161; -.
DR Antibodypedia; 809; 575 antibodies from 40 providers.
DR DNASU; 9636; -.
DR Ensembl; ENST00000649529.1; ENSP00000496832.1; ENSG00000187608.10.
DR GeneID; 9636; -.
DR KEGG; hsa:9636; -.
DR MANE-Select; ENST00000649529.1; ENSP00000496832.1; NM_005101.4; NP_005092.1.
DR UCSC; uc001acj.5; human.
DR CTD; 9636; -.
DR DisGeNET; 9636; -.
DR GeneCards; ISG15; -.
DR HGNC; HGNC:4053; ISG15.
DR HPA; ENSG00000187608; Tissue enhanced (salivary).
DR MalaCards; ISG15; -.
DR MIM; 147571; gene.
DR MIM; 616126; phenotype.
DR neXtProt; NX_P05161; -.
DR OpenTargets; ENSG00000187608; -.
DR Orphanet; 319563; Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency.
DR PharmGKB; PA28465; -.
DR VEuPathDB; HostDB:ENSG00000187608; -.
DR eggNOG; KOG0001; Eukaryota.
DR GeneTree; ENSGT00940000162007; -.
DR InParanoid; P05161; -.
DR OMA; QCTVFMN; -.
DR OrthoDB; 1367357at2759; -.
DR PhylomeDB; P05161; -.
DR TreeFam; TF338379; -.
DR PathwayCommons; P05161; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-168276; NS1 Mediated Effects on Host Pathways.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; P05161; -.
DR BioGRID-ORCS; 9636; 25 hits in 1081 CRISPR screens.
DR ChiTaRS; ISG15; human.
DR EvolutionaryTrace; P05161; -.
DR GeneWiki; ISG15; -.
DR GenomeRNAi; 9636; -.
DR Pharos; P05161; Tbio.
DR PRO; PR:P05161; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P05161; protein.
DR Bgee; ENSG00000187608; Expressed in decidua and 204 other tissues.
DR ExpressionAtlas; P05161; baseline and differential.
DR Genevisible; P05161; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0031386; F:protein tag; IBA:GO_Central.
DR GO; GO:0003735; F:structural constituent of ribosome; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0032020; P:ISG15-protein conjugation; IDA:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB.
DR GO; GO:0032461; P:positive regulation of protein oligomerization; IDA:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; IDA:UniProtKB.
DR GO; GO:0032649; P:regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR019956; Ubiquitin_dom.
DR Pfam; PF00240; ubiquitin; 2.
DR PRINTS; PR00348; UBIQUITIN.
DR SMART; SM00213; UBQ; 2.
DR SUPFAM; SSF54236; SSF54236; 2.
DR PROSITE; PS50053; UBIQUITIN_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Host-virus interaction; Immunity; Innate immunity;
KW Isopeptide bond; Reference proteome; Repeat; S-nitrosylation; Secreted;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2477469"
FT CHAIN 2..157
FT /note="Ubiquitin-like protein ISG15"
FT /id="PRO_0000035986"
FT PROPEP 158..165
FT /note="Removed in mature form"
FT /id="PRO_0000035987"
FT DOMAIN 2..78
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 79..157
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REGION 153..157
FT /note="Involved in the ligation of specific target
FT proteins"
FT /evidence="ECO:0000250"
FT MOTIF 152..157
FT /note="LRLRGG"
FT SITE 153
FT /note="Interacts with activating enzyme"
FT /evidence="ECO:0000250"
FT MOD_RES 78
FT /note="S-nitrosocysteine; alternate"
FT /evidence="ECO:0000269|PubMed:18606809"
FT DISULFID 78
FT /note="Interchain (with C-87 in UBE2N); alternate"
FT /evidence="ECO:0000269|PubMed:22693631"
FT CROSSLNK 157
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor proteins)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT VARIANT 83
FT /note="S -> N (in dbSNP:rs1921)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_016181"
FT MUTAGEN 44
FT /note="R->A: Does not affect ISG15 signaling, interaction
FT with ITGAL or activation of SRC family tyrosine kinases."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 83
FT /note="S->A: Does not affect ISG15 signaling, interaction
FT with ITGAL or activation of SRC family tyrosine kinases."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 96
FT /note="Y->L: Reduces ISG15 signaling. Strongly reduces
FT ISG15 signaling and abolishes interaction with ITGAL and
FT activation of SRC family tyrosine kinases; when associated
FT with D-102."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 99
FT /note="R->A: Strongly reduces ISG15 signaling and abolishes
FT interaction with ITGAL."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 101
FT /note="T->A: Strongly reduces ISG15 signaling and abolishes
FT interaction with ITGAL and activation of SRC family
FT tyrosine kinases."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 102
FT /note="Q->D: Reduces ISG15 signaling. Strongly reduces
FT ISG15 signaling and abolishes interaction with ITGAL and
FT activation of SRC family tyrosine kinases; when associated
FT with L-96."
FT /evidence="ECO:0000269|PubMed:29100055"
FT MUTAGEN 103
FT /note="T->A: Strongly reduces ISG15 signaling and abolishes
FT interaction with ITGAL."
FT /evidence="ECO:0000269|PubMed:29100055"
FT CONFLICT 35
FT /note="K -> N (in Ref. 2; AAA36128)"
FT /evidence="ECO:0000305"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:6BI8"
FT STRAND 14..18
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:6BI8"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:3RT3"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:7S6P"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:6BI8"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:3RT3"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:6FFA"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:6FFA"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:6FFA"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:6FFA"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:6FFA"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:5TL6"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:6FFA"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:6FFA"
SQ SEQUENCE 165 AA; 17888 MW; B6858A15AB0FFFDE CRC64;
MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS GVALQDRVPL
ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL TQTVAHLKQQ VSGLEGVQDD
LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM NLRLRGGGTE PGGRS
