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P05161

- ISG15_HUMAN

UniProt

P05161 - ISG15_HUMAN

Protein

Ubiquitin-like protein ISG15

Gene

ISG15

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade therby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity.19 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei153 – 1531Activating enzymeBy similarity

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. protein tag Source: Ensembl

    GO - Biological processi

    1. cytokine-mediated signaling pathway Source: Reactome
    2. defense response to bacterium Source: UniProtKB
    3. defense response to virus Source: UniProtKB
    4. innate immune response Source: Reactome
    5. ISG15-protein conjugation Source: UniProtKB
    6. modification-dependent protein catabolic process Source: Ensembl
    7. negative regulation of protein ubiquitination Source: UniProtKB
    8. negative regulation of type I interferon production Source: Reactome
    9. negative regulation of viral genome replication Source: UniProtKB
    10. positive regulation of erythrocyte differentiation Source: Ensembl
    11. regulation of interferon-gamma production Source: UniProtKB
    12. response to type I interferon Source: UniProtKB
    13. type I interferon signaling pathway Source: Reactome
    14. viral process Source: UniProtKB-KW

    Keywords - Biological processi

    Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_115831. ISG15 antiviral mechanism.
    REACT_25162. Interferon alpha/beta signaling.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin-like protein ISG15
    Alternative name(s):
    Interferon-induced 15 kDa protein
    Interferon-induced 17 kDa protein
    Short name:
    IP17
    Ubiquitin cross-reactive protein
    Short name:
    hUCRP
    Gene namesi
    Name:ISG15
    Synonyms:G1P2, UCRP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:4053. ISG15.

    Subcellular locationi

    Cytoplasm 1 Publication. Secreted 1 Publication
    Note: Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. extracellular region Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Secreted

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti319563. Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency.
    PharmGKBiPA28465.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 157156Ubiquitin-like protein ISG15PRO_0000035986Add
    BLAST
    Propeptidei158 – 1658Removed in mature formPRO_0000035987

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei78 – 781S-nitrosocysteine; alternate1 Publication
    Disulfide bondi78 – 78Interchain (with C-87 in UBE2N); alternate1 Publication
    Cross-linki157 – 157Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)PROSITE-ProRule annotation

    Post-translational modificationi

    S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.1 Publication
    Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases.2 Publications

    Keywords - PTMi

    Disulfide bond, Isopeptide bond, S-nitrosylation

    Proteomic databases

    MaxQBiP05161.
    PaxDbiP05161.
    PeptideAtlasiP05161.
    PRIDEiP05161.

    PTM databases

    PhosphoSiteiP05161.

    Expressioni

    Tissue specificityi

    Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons. Expressed in neutrophils, monocytes and lymphocytes. Enhanced expression seen in pancreatic adenocarcinoma, endometrial cancer, and bladder cancer, as compared to non-cancerous tissue. In bladder cancer, the increase in expression exhibits a striking positive correlation with more advanced stages of the disease.2 Publications

    Inductioni

    Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including certain genotoxic stresses.1 Publication

    Gene expression databases

    BgeeiP05161.
    CleanExiHS_ISG15.
    GenevestigatoriP05161.

    Organism-specific databases

    HPAiHPA004627.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked. Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) Probable. Interaction with influenza B NS1 protein inhibits its conjugation. Interacts with NEDD4.4 PublicationsCurated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FLNBO753694EBI-746466,EBI-352089
    PPM1BO756882EBI-746466,EBI-1047039

    Protein-protein interaction databases

    BioGridi114995. 179 interactions.
    DIPiDIP-29814N.
    IntActiP05161. 4 interactions.
    MINTiMINT-1440156.
    STRINGi9606.ENSP00000368699.

    Structurei

    Secondary structure

    1
    165
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 96
    Beta strandi14 – 185
    Helixi25 – 3612
    Helixi40 – 423
    Beta strandi43 – 486
    Beta strandi56 – 583
    Helixi60 – 634
    Beta strandi70 – 756
    Beta strandi82 – 876
    Beta strandi93 – 986
    Helixi104 – 11512
    Helixi119 – 1213
    Beta strandi122 – 1265
    Helixi137 – 1404
    Beta strandi147 – 1526

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1Z2MX-ray2.50A1-155[»]
    2HJ8NMR-A79-157[»]
    3PHXX-ray1.60B79-156[»]
    3PSEX-ray2.30B1-156[»]
    3R66X-ray2.30C/D1-157[»]
    3RT3X-ray2.01B1-158[»]
    3SDLX-ray2.29C/D1-157[»]
    ProteinModelPortaliP05161.
    SMRiP05161. Positions 4-154.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05161.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 7877Ubiquitin-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini79 – 15779Ubiquitin-like 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni153 – 1575Involved in the ligation of specific target proteinsBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi152 – 1576LRLRGG

    Domaini

    Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein (PubMed:18356159).1 Publication

    Sequence similaritiesi

    Contains 2 ubiquitin-like domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG5272.
    HOGENOMiHOG000233942.
    HOVERGENiHBG000057.
    InParanoidiP05161.
    KOiK12159.
    OMAiFWLTFEG.
    OrthoDBiEOG7B05FG.
    PhylomeDBiP05161.
    TreeFamiTF338379.

    Family and domain databases

    InterProiIPR019956. Ubiquitin.
    IPR000626. Ubiquitin-like.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PfamiPF00240. ubiquitin. 2 hits.
    [Graphical view]
    PRINTSiPR00348. UBIQUITIN.
    SMARTiSM00213. UBQ. 2 hits.
    [Graphical view]
    SUPFAMiSSF54236. SSF54236. 2 hits.
    PROSITEiPS50053. UBIQUITIN_2. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P05161-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS    50
    GVALQDRVPL ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL 100
    TQTVAHLKQQ VSGLEGVQDD LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM 150
    NLRLRGGGTE PGGRS 165
    Length:165
    Mass (Da):17,888
    Last modified:January 23, 2007 - v5
    Checksum:iB6858A15AB0FFFDE
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti35 – 351K → N in AAA36128. (PubMed:3476954)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti83 – 831S → N.3 Publications
    Corresponds to variant rs1921 [ dbSNP | Ensembl ].
    VAR_016181

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13755 mRNA. Translation: AAA36038.1.
    M21786 Genomic DNA. Translation: AAA36128.1.
    AY168648 mRNA. Translation: AAN86983.1.
    BT007297 mRNA. Translation: AAP35961.1.
    AL645608 Genomic DNA. Translation: CAI15574.1.
    CH471183 Genomic DNA. Translation: EAW56295.1.
    BC009507 mRNA. Translation: AAH09507.1.
    CCDSiCCDS6.1.
    PIRiA28304. A28138.
    RefSeqiNP_005092.1. NM_005101.3.
    UniGeneiHs.458485.

    Genome annotation databases

    EnsembliENST00000379389; ENSP00000368699; ENSG00000187608.
    GeneIDi9636.
    KEGGihsa:9636.
    UCSCiuc001acj.4. human.

    Polymorphism databases

    DMDMi52001470.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M13755 mRNA. Translation: AAA36038.1 .
    M21786 Genomic DNA. Translation: AAA36128.1 .
    AY168648 mRNA. Translation: AAN86983.1 .
    BT007297 mRNA. Translation: AAP35961.1 .
    AL645608 Genomic DNA. Translation: CAI15574.1 .
    CH471183 Genomic DNA. Translation: EAW56295.1 .
    BC009507 mRNA. Translation: AAH09507.1 .
    CCDSi CCDS6.1.
    PIRi A28304. A28138.
    RefSeqi NP_005092.1. NM_005101.3.
    UniGenei Hs.458485.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1Z2M X-ray 2.50 A 1-155 [» ]
    2HJ8 NMR - A 79-157 [» ]
    3PHX X-ray 1.60 B 79-156 [» ]
    3PSE X-ray 2.30 B 1-156 [» ]
    3R66 X-ray 2.30 C/D 1-157 [» ]
    3RT3 X-ray 2.01 B 1-158 [» ]
    3SDL X-ray 2.29 C/D 1-157 [» ]
    ProteinModelPortali P05161.
    SMRi P05161. Positions 4-154.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114995. 179 interactions.
    DIPi DIP-29814N.
    IntActi P05161. 4 interactions.
    MINTi MINT-1440156.
    STRINGi 9606.ENSP00000368699.

    PTM databases

    PhosphoSitei P05161.

    Polymorphism databases

    DMDMi 52001470.

    Proteomic databases

    MaxQBi P05161.
    PaxDbi P05161.
    PeptideAtlasi P05161.
    PRIDEi P05161.

    Protocols and materials databases

    DNASUi 9636.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000379389 ; ENSP00000368699 ; ENSG00000187608 .
    GeneIDi 9636.
    KEGGi hsa:9636.
    UCSCi uc001acj.4. human.

    Organism-specific databases

    CTDi 9636.
    GeneCardsi GC01P000938.
    HGNCi HGNC:4053. ISG15.
    HPAi HPA004627.
    MIMi 147571. gene.
    neXtProti NX_P05161.
    Orphaneti 319563. Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency.
    PharmGKBi PA28465.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5272.
    HOGENOMi HOG000233942.
    HOVERGENi HBG000057.
    InParanoidi P05161.
    KOi K12159.
    OMAi FWLTFEG.
    OrthoDBi EOG7B05FG.
    PhylomeDBi P05161.
    TreeFami TF338379.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.
    REACT_25162. Interferon alpha/beta signaling.
    REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Miscellaneous databases

    EvolutionaryTracei P05161.
    GeneWikii ISG15.
    GenomeRNAii 9636.
    NextBioi 36167.
    PROi P05161.
    SOURCEi Search...

    Gene expression databases

    Bgeei P05161.
    CleanExi HS_ISG15.
    Genevestigatori P05161.

    Family and domain databases

    InterProi IPR019956. Ubiquitin.
    IPR000626. Ubiquitin-like.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    Pfami PF00240. ubiquitin. 2 hits.
    [Graphical view ]
    PRINTSi PR00348. UBIQUITIN.
    SMARTi SM00213. UBQ. 2 hits.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 2 hits.
    PROSITEi PS50053. UBIQUITIN_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence."
      Blomstrom D.C., Fahey D., Kutny R., Korant B.D., Knight E. Jr.
      J. Biol. Chem. 261:8811-8816(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element."
      Reich N., Evans B., Levy D., Fahey D., Knight E. Jr., Darnell J.E. Jr.
      Proc. Natl. Acad. Sci. U.S.A. 84:6394-6398(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "A 15-kDa interferon-induced protein is derived by COOH-terminal processing of a 17-kDa precursor."
      Knight E. Jr., Fahey D., Cordova B., Hillman M. Jr., Kutny R., Reich N., Blomstrom D.C.
      J. Biol. Chem. 263:4520-4522(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING.
    4. Erratum
      Knight E. Jr., Fahey D., Cordova B., Hillman M. Jr., Kutny R., Reich N., Blomstrom D.C.
      J. Biol. Chem. 263:10040-10040(1988)
    5. "Conjugation by ubiquitin-like proteins."
      Kamitani T., Fukuda-Kamitani T.
      Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-83.
      Tissue: Testis.
    6. "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], VARIANT ASN-83.
    7. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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], VARIANT ASN-83.
      Tissue: Colon.
    10. "A 15-kD interferon-induced protein and its 17-kD precursor: expression in Escherichia coli, purification, and characterization."
      Feltham N., Hillman M. Jr., Cordova B., Fahey D., Larsen B., Blomstrom D.C., Knight E. Jr.
      J. Interferon Res. 9:493-507(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-38 AND 151-165, PROTEOLYTIC PROCESSING.
    11. "Interferon induces a 15-kilodalton protein exhibiting marked homology to ubiquitin."
      Haas A.L., Ahrens P., Bright P.M., Ankel H.
      J. Biol. Chem. 262:11315-11323(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: SIMILARITY TO UBIQUITIN.
    12. "The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins."
      Loeb K.R., Haas A.L.
      J. Biol. Chem. 267:7806-7813(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern."
      Loeb K.R., Haas A.L.
      Mol. Cell. Biol. 14:8408-8419(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from that of ubiquitin."
      Narasimhan J., Potter J.L., Haas A.L.
      J. Biol. Chem. 271:324-330(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "IFN-induced 15-kDa protein is released from human lymphocytes and monocytes."
      Knight E. Jr., Cordova B.
      J. Immunol. 146:2280-2284(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    16. "Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues."
      Lowe J., McDermott H., Loeb K., Landon M., Haas A.L., Mayer R.J.
      J. Pathol. 177:163-169(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    17. "Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein."
      Yuan W., Krug R.M.
      EMBO J. 20:362-371(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBE1L AND INFLUENZA B NS1.
    18. "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.
    19. "The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-alpha/beta-induced ubiquitin-like protein."
      Zhao C., Beaudenon S.L., Kelley M.L., Waddell M.B., Yuan W., Schulman B.A., Huibregtse J.M., Krug R.M.
      Proc. Natl. Acad. Sci. U.S.A. 101:7578-7582(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH UBE2E2.
    20. "ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating activity."
      Takeuchi T., Yokosawa H.
      Biochem. Biophys. Res. Commun. 336:9-13(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBE2N ISGYLATION.
    21. "Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme."
      Takeuchi T., Iwahara S., Saeki Y., Sasajima H., Yokosawa H.
      J. Biochem. 138:711-719(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBE2E1 AND UBE2L6 ISGYLATION.
    22. "Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways."
      Zhao C., Denison C., Huibregtse J.M., Gygi S.P., Krug R.M.
      Proc. Natl. Acad. Sci. U.S.A. 102:10200-10205(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IFIT1; DDX58 AND MX1 ISGYLATION.
    23. "Negative regulation of protein phosphatase 2Cbeta by ISG15 conjugation."
      Takeuchi T., Kobayashi T., Tamura S., Yokosawa H.
      FEBS Lett. 580:4521-4526(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PPM1B ISGYLATION.
    24. "Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15."
      Okumura A., Lu G., Pitha-Rowe I., Pitha P.M.
      Proc. Natl. Acad. Sci. U.S.A. 103:1440-1445(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HIV-1 RESTRICTION.
    25. "Different roles for two ubiquitin-like domains of ISG15 in protein modification."
      Chang Y.G., Yan X.Z., Xie Y.Y., Gao X.C., Song A.X., Zhang D.E., Hu H.Y.
      J. Biol. Chem. 283:13370-13377(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAINS UBIQUITIN-LIKE 1 AND 2.
    26. "Nitrosylation of ISG15 prevents the disulfide bond-mediated dimerization of ISG15 and contributes to effective ISGylation."
      Okumura F., Lenschow D.J., Zhang D.E.
      J. Biol. Chem. 283:24484-24488(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: S-NITROSYLATION AT CYS-78.
    27. "ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity."
      Okumura A., Pitha P.M., Harty R.N.
      Proc. Natl. Acad. Sci. U.S.A. 105:3974-3979(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN EBOLA VIRUS RESTRICTION, INTERACTION WITH NEDD4.
    28. "ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway."
      Jeon Y.J., Choi J.S., Lee J.Y., Yu K.R., Kim S.M., Ka S.H., Oh K.H., Kim K.I., Zhang D.E., Bang O.S., Chung C.H.
      EMBO Rep. 10:374-380(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN FLNB ISGYLATION.
    29. "Antiviral activity of innate immune protein ISG15."
      Harty R.N., Pitha P.M., Okumura A.
      J. Innate Immun. 1:397-404(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    30. "Interferon-induced ISG15 conjugation inhibits influenza A virus gene expression and replication in human cells."
      Hsiang T.Y., Zhao C., Krug R.M.
      J. Virol. 83:5971-5977(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INFLUENZA A VIRUS RESTRICTION.
    31. Cited for: REVIEW.
    32. "Emerging role of ISG15 in antiviral immunity."
      Skaug B., Chen Z.J.
      Cell 143:187-190(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    33. "The interferon stimulated gene 15 functions as a proviral factor for the hepatitis C virus and as a regulator of the IFN response."
      Broering R., Zhang X., Kottilil S., Trippler M., Jiang M., Lu M., Gerken G., Schlaak J.F.
      Gut 59:1111-1119(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    34. "Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification."
      Shi H.X., Yang K., Liu X., Liu X.Y., Wei B., Shan Y.F., Zhu L.H., Wang C.
      Mol. Cell. Biol. 30:2424-2436(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IRF3 ISGYLATION.
    35. "ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells."
      Zhao C., Hsiang T.Y., Kuo R.L., Krug R.M.
      Proc. Natl. Acad. Sci. U.S.A. 107:2253-2258(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN INFLUENZA A VIRUS NS1 ISGYLATION.
    36. Cited for: REVIEW.
    37. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    38. "Interferon-stimulated gene 15 and the protein ISGylation system."
      Zhang D., Zhang D.E.
      J. Interferon Cytokine Res. 31:119-130(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    39. "Mechanism of inhibition of retrovirus release from cells by interferon-induced gene ISG15."
      Kuang Z., Seo E.J., Leis J.
      J. Virol. 85:7153-7161(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CHMP5; CHMP2A; CHMP4B AND CHMP6 ISGYLATION.
    40. "Budding of enveloped viruses: interferon-induced ISG15-antivirus mechanisms targeting the release process."
      Seo E.J., Leis J.
      Adv. Virol. 2012:532723-532723(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    41. Cited for: REVIEW.
    42. "Covalent protein modification with ISG15 via a conserved cysteine in the hinge region."
      Bade V.N., Nickels J., Keusekotten K., Praefcke G.J.
      PLoS ONE 7:E38294-E38294(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN UBE2N AND UBA7 ISGYLATION, DISULFIDE BOND.
    43. Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    44. "ISG15 regulates IFN-? immunity in human mycobacterial disease."
      Fan J.B., Zhang D.E.
      Cell Res. 23:173-175(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    45. "ISG15: leading a double life as a secreted molecule."
      Bogunovic D., Boisson-Dupuis S., Casanova J.L.
      Exp. Mol. Med. 45:E18-E18(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    46. "Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation."
      Okumura F., Okumura A.J., Uematsu K., Hatakeyama S., Zhang D.E., Kamura T.
      J. Biol. Chem. 288:2839-2847(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN EIF2AK2 ISGYLATION.
    47. "Interferon-induced ISG15 pathway: an ongoing virus-host battle."
      Zhao C., Collins M.N., Hsiang T.Y., Krug R.M.
      Trends Microbiol. 21:181-186(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    48. "Crystal structure of the interferon-induced ubiquitin-like protein ISG15."
      Narasimhan J., Wang M., Fu Z., Klein J.M., Haas A.L., Kim J.J.
      J. Biol. Chem. 280:27356-27365(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-155 OF MUTANT SER-78.
    49. "Solution NMR structure of the C-terminal domain of the interferon alpha-inducible ISG15 protein from Homo sapiens."
      Northeast structural genomics consortium (NESG)
      Submitted (FEB-2009) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 79-157.

    Entry informationi

    Entry nameiISG15_HUMAN
    AccessioniPrimary (citable) accession number: P05161
    Secondary accession number(s): Q5SVA4, Q7Z2G2, Q96GF0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 165 of the entry and version 5 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

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3