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P05161

- ISG15_HUMAN

UniProt

P05161 - ISG15_HUMAN

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Protein

Ubiquitin-like protein ISG15

Gene

ISG15

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

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 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
Complete GO annotation...

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
Complete GO annotation...

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. 183 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.
GeneTreeiENSGT00760000119340.
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

        10         20         30         40         50
MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS
60 70 80 90 100
GVALQDRVPL ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL
110 120 130 140 150
TQTVAHLKQQ VSGLEGVQDD LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM
160
NLRLRGGGTE PGGRS
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. 183 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.
GeneTreei ENSGT00760000119340.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 166 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

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