Q64339 (ISG15_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	Isg15
Synonyms:	G1p2, Ucrp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	161 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections By similarity. In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy.
Subunit structure	Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) By similarity.
Subcellular location	Cytoplasm. Secreted By similarity. Note: UCRP conjugates seem to be noncovalently associated with the intermediate filaments and distributed in a punctate pattern. Also secreted By similarity.
Induction	By type I interferons.
Sequence similarities	Contains 2 ubiquitin-like domains.
Mass spectrometry	Molecular mass is 17015 Da from positions 2 - 155. Determined by MALDI. Ref.5

Ontologies

Keywords
Biological process	Antiviral defense Ubl conjugation pathway
Cellular component	Cytoplasm Secreted
Domain	Repeat
PTM	Isopeptide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ISG15-protein conjugation Inferred from direct assay PubMed 16139798. Source: MGI defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from direct assay PubMed 15485925. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein tag Inferred from direct assay PubMed 16139798. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 155	154	Ubiquitin-like protein ISG15		PRO_0000035988
	Propeptide	156 – 161	6	Removed in mature form By similarity		PRO_0000035989
Regions
	Domain	2 – 76	75	Ubiquitin-like 1
	Domain	77 – 155	79	Ubiquitin-like 2
	Region	151 – 155	5	Involved in the ligation of specific target proteins By similarity
Sites
	Binding site	151	1	Activating enzyme By similarity
Amino acid modifications
	Cross-link	155		Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins) By similarity
Experimental info
	Sequence conflict	111 – 115	5	QREQV → SGTS in CAA39939. Ref.1
	Sequence conflict	111 – 115	5	QREQV → SGTS in AAB02697. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q64339 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 9C70D9A507979171	FASTA	161	17,898
	10 20 30 40 50 60 MAWDLKVKML GGNDFLVSVT NSMTVSELKK QIAQKIGVPA FQQRLAHQTA VLQDGLTLSS 70 80 90 100 110 120 LGLGPSSTVM LVVQNCSEPL SILVRNERGH SNIYEVFLTQ TVDTLKKKVS QREQVHEDQF 130 140 150 160 WLSFEGRPME DKELLGEYGL KPQCTVIKHL RLRGGGGDQC A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence and deduced amino acid sequence of a cDNA encoding an interferon-induced mouse 15-KDa protein." Fahey D. Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Sequence differences between murine ISG15, human ISG15 and ubiquitin: a functional divergence from ubiquitin." Garlie N.K., Haas A.L., D'Cunha J., Schilling D., Knight E. Jr., Borden E.C. Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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]. Tissue: Mammary gland.
[4]	"Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog." Hamerman J.A., Hayashi F., Schroeder L.A., Gygi S.P., Haas A.L., Hampson L., Coughlin P., Aebersold R., Aderem A. J. Immunol. 168:2415-2423(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 9-30; 36-44 AND 89-106, CONJUGATION TO SERPINA3G.
[5]	"Identification of a ubiquitin family protein as a novel neutrophil chemotactic factor." Owhashi M., Taoka Y., Ishii K., Nakazawa S., Uemura H., Kambara H. Biochem. Biophys. Res. Commun. 309:533-539(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, CHEMOTACTIC ACTIVITY, MASS SPECTROMETRY.
[6]	"High-throughput immunoblotting. Ubiquitin-like protein ISG15 modifies key regulators of signal transduction." Malakhov M.P., Kim K.I., Malakhova O.A., Jacobs B.S., Borden E.C., Zhang D.-E. J. Biol. Chem. 278:16608-16613(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CONJUGATION TO JAK1; MAPK3 AND PLCG1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X56602 mRNA. Translation: CAA39939.1. U58202 Genomic DNA. Translation: AAB02697.1. BC031424 mRNA. Translation: AAH31424.1. BC083156 mRNA. Translation: AAH83156.1.
IPI	IPI00555085.
PIR	S26434.
RefSeq	NP_056598.2. NM_015783.3.
UniGene	Mm.451527. Mm.4950.
3D structure databases
ProteinModelPortal	Q64339.
SMR	Q64339. Positions 3-154.
ModBase	Search...
PTM databases
PhosphoSite	Q64339.
Proteomic databases
PaxDb	Q64339.
PRIDE	Q64339.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000085425; ENSMUSP00000082548; ENSMUSG00000035692.
GeneID	100038882.
KEGG	mmu:100038882.
Organism-specific databases
CTD	9636.
MGI	MGI:1855694. Isg15.
Phylogenomic databases
eggNOG	COG5272.
GeneTree	ENSGT00550000074658.
HOGENOM	HOG000233942.
HOVERGEN	HBG000057.
InParanoid	Q64339.
KO	K12159.
OMA	FWLTFEG.
OrthoDB	EOG4CNQSF.
Gene expression databases
ArrayExpress	Q64339.
Bgee	Q64339.
CleanEx	MM_ISG15.
Genevestigator	Q64339.
Family and domain databases
InterPro	IPR000626. Ubiquitin. IPR019955. Ubiquitin_supergroup. [Graphical view]
Pfam	PF00240. ubiquitin. 2 hits. [Graphical view]
SMART	SM00213. UBQ. 2 hits. [Graphical view]
PROSITE	PS50053. UBIQUITIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	445160.
SOURCE	Search...

Entry information

Entry name

ISG15_MOUSE

Accession

Primary (citable) accession number: Q64339
Secondary accession number(s): Q8K0H3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 114 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program