Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P05161 (ISG15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ISG15
Synonyms:G1P2, UCRP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length165 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.12 Ref.13 Ref.14 Ref.15 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.27 Ref.28 Ref.30 Ref.33 Ref.34 Ref.35 Ref.39 Ref.42 Ref.43 Ref.46

Subunit structure

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. Ref.17 Ref.19 Ref.27 Ref.42

Subcellular location

Cytoplasm. Secreted. Note: Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins. Ref.43

Tissue specificity

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. Ref.16 Ref.43

Induction

Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including certain genotoxic stresses. Ref.43

Domain

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 (Ref.25). Ref.25

Post-translational modification

S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.

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. Ref.3 Ref.10

Sequence similarities

Contains 2 ubiquitin-like domains.

Ontologies

Keywords
   Biological processAntiviral defense
Host-virus interaction
Immunity
Innate immunity
Ubl conjugation pathway
   Cellular componentCytoplasm
Secreted
   Coding sequence diversityPolymorphism
   DomainRepeat
   PTMDisulfide bond
Isopeptide bond
S-nitrosylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processISG15-protein conjugation

Inferred from direct assay Ref.39. Source: UniProtKB

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to bacterium

Inferred from mutant phenotype Ref.43. Source: UniProtKB

defense response to virus

Inferred from mutant phenotype Ref.30. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

modification-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein ubiquitination

Inferred from direct assay Ref.27. Source: UniProtKB

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

negative regulation of viral genome replication

Inferred from mutant phenotype Ref.30. Source: UniProtKB

positive regulation of erythrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of interferon-gamma production

Inferred from mutant phenotype Ref.43. Source: UniProtKB

response to type I interferon

Inferred from direct assay Ref.43. Source: UniProtKB

type I interferon signaling pathway

Traceable author statement. Source: Reactome

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

extracellular region

Inferred from direct assay Ref.43. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.27. Source: UniProtKB

protein tag

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 157156Ubiquitin-like protein ISG15
PRO_0000035986
Propeptide158 – 1658Removed in mature form
PRO_0000035987

Regions

Domain2 – 7877Ubiquitin-like 1
Domain79 – 15779Ubiquitin-like 2
Region153 – 1575Involved in the ligation of specific target proteins By similarity
Motif152 – 1576LRLRGG

Sites

Binding site1531Activating enzyme By similarity

Amino acid modifications

Modified residue781S-nitrosocysteine; alternate Ref.26
Disulfide bond78Interchain (with C-87 in UBE2N); alternate Ref.42
Cross-link157Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins) By similarity

Natural variations

Natural variant831S → N. Ref.5 Ref.6 Ref.9
Corresponds to variant rs1921 [ dbSNP | Ensembl ].
VAR_016181

Experimental info

Sequence conflict351K → N in AAA36128. Ref.2

Secondary structure

............................. 165
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05161 [UniParc].

Last modified January 23, 2007. Version 5.
Checksum: B6858A15AB0FFFDE

FASTA16517,888
        10         20         30         40         50         60 
MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS GVALQDRVPL 

        70         80         90        100        110        120 
ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL TQTVAHLKQQ VSGLEGVQDD 

       130        140        150        160 
LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM NLRLRGGGTE PGGRS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"ISG15 and immune diseases."
Jeon Y.J., Yoo H.M., Chung C.H.
Biochim. Biophys. Acta 1802:485-496(2010) [PubMed] [Europe PMC] [Abstract]
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]"Antiviral properties of ISG15."
Lenschow D.J.
Viruses 2:2154-2168(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[37]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"IFNs, ISGylation and cancer: Cui prodest?"
Sgorbissa A., Brancolini C.
Cytokine Growth Factor Rev. 23:307-314(2012) [PubMed] [Europe PMC] [Abstract]
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]"Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency."
Bogunovic D., Byun M., Durfee L.A., Abhyankar A., Sanal O., Mansouri D., Salem S., Radovanovic I., Grant A.V., Adimi P., Mansouri N., Okada S., Bryant V.L., Kong X.F., Kreins A., Velez M.M., Boisson B., Khalilzadeh S. expand/collapse author list , Ozcelik U., Darazam I.A., Schoggins J.W., Rice C.M., Al-Muhsen S., Behr M., Vogt G., Puel A., Bustamante J., Gros P., Huibregtse J.M., Abel L., Boisson-Dupuis S., Casanova J.L.
Science 337:1684-1688(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS6.1.
PIRA28138. A28304.
RefSeqNP_005092.1. NM_005101.3.
UniGeneHs.458485.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP05161.
SMRP05161. Positions 4-154.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114995. 178 interactions.
DIPDIP-29814N.
IntActP05161. 4 interactions.
MINTMINT-1440156.
STRING9606.ENSP00000368699.

PTM databases

PhosphoSiteP05161.

Polymorphism databases

DMDM52001470.

Proteomic databases

MaxQBP05161.
PaxDbP05161.
PeptideAtlasP05161.
PRIDEP05161.

Protocols and materials databases

DNASU9636.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379389; ENSP00000368699; ENSG00000187608.
GeneID9636.
KEGGhsa:9636.
UCSCuc001acj.4. human.

Organism-specific databases

CTD9636.
GeneCardsGC01P000938.
HGNCHGNC:4053. ISG15.
HPAHPA004627.
MIM147571. gene.
neXtProtNX_P05161.
Orphanet319563. Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency.
PharmGKBPA28465.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5272.
HOGENOMHOG000233942.
HOVERGENHBG000057.
InParanoidP05161.
KOK12159.
OMAFWLTFEG.
OrthoDBEOG7B05FG.
PhylomeDBP05161.
TreeFamTF338379.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP05161.
CleanExHS_ISG15.
GenevestigatorP05161.

Family and domain databases

InterProIPR019956. Ubiquitin.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF00240. ubiquitin. 2 hits.
[Graphical view]
PRINTSPR00348. UBIQUITIN.
SMARTSM00213. UBQ. 2 hits.
[Graphical view]
SUPFAMSSF54236. SSF54236. 2 hits.
PROSITEPS50053. UBIQUITIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05161.
GeneWikiISG15.
GenomeRNAi9636.
NextBio36167.
PROP05161.
SOURCESearch...

Entry information

Entry nameISG15_HUMAN
AccessionPrimary (citable) accession number: P05161
Secondary accession number(s): Q5SVA4, Q7Z2G2, Q96GF0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 163 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM