#ID(s) interactor A	ID(s) interactor B	Alt. ID(s) interactor A	Alt. ID(s) interactor B	Alias(es) interactor A	Alias(es) interactor B	Interaction detection method(s)	Publication 1st author(s)	Publication Identifier(s)	Taxid interactor A	Taxid interactor B	Interaction type(s)	Source database(s)	Interaction identifier(s)	Confidence value(s)	Expansion method(s)	Biological role(s) interactor A	Biological role(s) interactor B	Experimental role(s) interactor A	Experimental role(s) interactor B	Type(s) interactor A	Type(s) interactor B	Xref(s) interactor A	Xref(s) interactor B	Interaction Xref(s)	Annotation(s) interactor A	Annotation(s) interactor B	Interaction annotation(s)	Host organism(s)	Interaction parameter(s)	Creation date	Update date	Checksum(s) interactor A	Checksum(s) interactor B	Interaction Checksum(s)	Negative	Feature(s) interactor A	Feature(s) interactor B	Stoichiometry(s) interactor A	Stoichiometry(s) interactor B	Identification method participant A	Identification method participant B
uniprotkb:Q64339	uniprotkb:Q9WTV6	intact:EBI-8345781|uniprotkb:Q8K0H3|intact:MINT-4139466|ensembl:ENSMUSP00000082548	intact:EBI-9119995|uniprotkb:Q3U7P3|ensembl:ENSMUSP00000032198	psi-mi:isg15_mouse(display_long)|uniprotkb:Isg15(gene name)|psi-mi:Isg15(display_short)|uniprotkb:G1p2(gene name synonym)|uniprotkb:Ucrp(gene name synonym)|uniprotkb:Interferon-induced 15 kDa protein(gene name synonym)|uniprotkb:Interferon-induced 17 kDa protein(gene name synonym)|uniprotkb:Ubiquitin cross-reactive protein(gene name synonym)	psi-mi:ubp18_mouse(display_long)|uniprotkb:Usp18(gene name)|psi-mi:Usp18(display_short)|uniprotkb:Ubp43(gene name synonym)|uniprotkb:43 kDa ISG15-specific protease(gene name synonym)|uniprotkb:ISG15-specific-processing protease(gene name synonym)|uniprotkb:Ubl thioesterase 18(gene name synonym)	psi-mi:"MI:1247"(microscale thermophoresis)	Basters et al. (2014)	pubmed:24533902|imex:IM-22234	taxid:10090(mouse)|taxid:10090(Mus musculus)	taxid:10090(mouse)|taxid:10090(Mus musculus)	psi-mi:"MI:0407"(direct interaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-9119984|imex:IM-22234-1	-	-	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0499"(unspecified role)	psi-mi:"MI:0497"(neutral component)	psi-mi:"MI:0497"(neutral component)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_056598.2|ensembl:ENSMUSG00000035692(gene)|ensembl:ENSMUST00000085425(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005737"(cytoplasm)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|go:"GO:0009617"(response to bacterium)|go:"GO:0019941"(modification-dependent protein catabolic process)|go:"GO:0022627"(cytosolic small ribosomal subunit)|go:"GO:0030501"(positive regulation of bone mineralization)|go:"GO:0031386"(protein tag)|go:"GO:0031397"(negative regulation of protein ubiquitination)|go:"GO:0031625"(ubiquitin protein ligase binding)|go:"GO:0032020"(ISG15-protein conjugation)|go:"GO:0032461"(positive regulation of protein oligomerization)|go:"GO:0032649"(regulation of interferon-gamma production)|go:"GO:0032728"(positive regulation of interferon-beta production)|go:"GO:0032729"(positive regulation of interferon-gamma production)|go:"GO:0032733"(positive regulation of interleukin-10 production)|go:"GO:0034340"(response to type I interferon)|go:"GO:0042742"(defense response to bacterium)|go:"GO:0045071"(negative regulation of viral genome replication)|go:"GO:0045648"(positive regulation of erythrocyte differentiation)|go:"GO:0051607"(defense response to virus)|go:"GO:0060339"(negative regulation of type I interferon-mediated signaling pathway)|go:"GO:0070585"(protein localization to mitochondrion)|interpro:IPR000626(Ubiquitin)|interpro:IPR029071|mint:Q64339|rcsb pdb:5CHF|rcsb pdb:5CHV|rcsb pdb:5CHW|rcsb pdb:5JZE|rcsb pdb:5TL7|rcsb pdb:5TLA|rcsb pdb:6J62|rcsb pdb:6YVA|reactome:R-MMU-1169408|reactome:R-MMU-5656169	refseq:NP_036039.2|ensembl:ENSMUSG00000030107(gene)|ensembl:ENSMUST00000032198(transcript)|go:"GO:0004197"(cysteine-type endopeptidase activity)|go:"GO:0004843"(thiol-dependent deubiquitinase)|go:"GO:0005634"(nucleus)|go:"GO:0005829"(cytosol)|go:"GO:0006511"(ubiquitin-dependent protein catabolic process)|go:"GO:0009617"(response to bacterium)|go:"GO:0016579"(protein deubiquitination)|go:"GO:0019785"(ISG15-specific protease activity)|go:"GO:0035634"(response to stilbenoid)|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0050727"(regulation of inflammatory response)|go:"GO:0060339"(negative regulation of type I interferon-mediated signaling pathway)|interpro:IPR001394(Peptidase C19, ubiquitin carboxyl-terminal hydrolase 2)|interpro:IPR018200|interpro:IPR028889|interpro:IPR038765|rcsb pdb:5CHT|rcsb pdb:5CHV|reactome:R-MMU-1169408|reactome:R-MMU-5689880|reactome:R-MMU-912694	-	function:"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"|comment:mint|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	-	figure legend:f3a|comment:"Purified ISG15-C76S and fluorescence-labelled USP18 were used for microscale  thermophoresis to determine the binding affinity. The binding data could be fitted assuming a  1:1 stoichiometry of USP18 and ISG15-C76S in the formed complex, showing that ISG15  bound specifically to one site. The USP18-ISG15 complex displayed a Kd of 1.3±0.2 FM (Fig.  3)."|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kd:1.3x10^-6	2014/02/07	2014/10/16	rogid:rLwDq3/OLBVXU0U9MVyiTeULqog10090	rogid:O0NdHT+5B0FrZAHxFjPRBQv/6HY10090	intact-crc:8A403DA58454C41C|rigid:GiZOD3rFy7McSSX/+5on4TETPr0	false	-	-	-	-	psi-mi:"MI:0396"(predetermined participant)	psi-mi:"MI:0396"(predetermined participant)
uniprotkb:Q64339	uniprotkb:Q9WTV6	intact:EBI-8345781|uniprotkb:Q8K0H3|intact:MINT-4139466|ensembl:ENSMUSP00000082548	intact:EBI-9119995|uniprotkb:Q3U7P3|ensembl:ENSMUSP00000032198	psi-mi:isg15_mouse(display_long)|uniprotkb:Isg15(gene name)|psi-mi:Isg15(display_short)|uniprotkb:G1p2(gene name synonym)|uniprotkb:Ucrp(gene name synonym)|uniprotkb:Interferon-induced 15 kDa protein(gene name synonym)|uniprotkb:Interferon-induced 17 kDa protein(gene name synonym)|uniprotkb:Ubiquitin cross-reactive protein(gene name synonym)	psi-mi:ubp18_mouse(display_long)|uniprotkb:Usp18(gene name)|psi-mi:Usp18(display_short)|uniprotkb:Ubp43(gene name synonym)|uniprotkb:43 kDa ISG15-specific protease(gene name synonym)|uniprotkb:ISG15-specific-processing protease(gene name synonym)|uniprotkb:Ubl thioesterase 18(gene name synonym)	psi-mi:"MI:0415"(enzymatic study)	Basters et al. (2014)	pubmed:24533902|imex:IM-22234	taxid:10090(mouse)|taxid:10090(Mus musculus)	taxid:10090(mouse)|taxid:10090(Mus musculus)	psi-mi:"MI:0194"(cleavage reaction)	psi-mi:"MI:0471"(MINT)	intact:EBI-9120027|imex:IM-22234-2	-	-	psi-mi:"MI:0502"(enzyme target)	psi-mi:"MI:0501"(enzyme)	psi-mi:"MI:0497"(neutral component)	psi-mi:"MI:0497"(neutral component)	psi-mi:"MI:0326"(protein)	psi-mi:"MI:0326"(protein)	refseq:NP_056598.2|ensembl:ENSMUSG00000035692(gene)|ensembl:ENSMUST00000085425(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005737"(cytoplasm)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|go:"GO:0009617"(response to bacterium)|go:"GO:0019941"(modification-dependent protein catabolic process)|go:"GO:0022627"(cytosolic small ribosomal subunit)|go:"GO:0030501"(positive regulation of bone mineralization)|go:"GO:0031386"(protein tag)|go:"GO:0031397"(negative regulation of protein ubiquitination)|go:"GO:0031625"(ubiquitin protein ligase binding)|go:"GO:0032020"(ISG15-protein conjugation)|go:"GO:0032461"(positive regulation of protein oligomerization)|go:"GO:0032649"(regulation of interferon-gamma production)|go:"GO:0032728"(positive regulation of interferon-beta production)|go:"GO:0032729"(positive regulation of interferon-gamma production)|go:"GO:0032733"(positive regulation of interleukin-10 production)|go:"GO:0034340"(response to type I interferon)|go:"GO:0042742"(defense response to bacterium)|go:"GO:0045071"(negative regulation of viral genome replication)|go:"GO:0045648"(positive regulation of erythrocyte differentiation)|go:"GO:0051607"(defense response to virus)|go:"GO:0060339"(negative regulation of type I interferon-mediated signaling pathway)|go:"GO:0070585"(protein localization to mitochondrion)|interpro:IPR000626(Ubiquitin)|interpro:IPR029071|mint:Q64339|rcsb pdb:5CHF|rcsb pdb:5CHV|rcsb pdb:5CHW|rcsb pdb:5JZE|rcsb pdb:5TL7|rcsb pdb:5TLA|rcsb pdb:6J62|rcsb pdb:6YVA|reactome:R-MMU-1169408|reactome:R-MMU-5656169	refseq:NP_036039.2|ensembl:ENSMUSG00000030107(gene)|ensembl:ENSMUST00000032198(transcript)|go:"GO:0004197"(cysteine-type endopeptidase activity)|go:"GO:0004843"(thiol-dependent deubiquitinase)|go:"GO:0005634"(nucleus)|go:"GO:0005829"(cytosol)|go:"GO:0006511"(ubiquitin-dependent protein catabolic process)|go:"GO:0009617"(response to bacterium)|go:"GO:0016579"(protein deubiquitination)|go:"GO:0019785"(ISG15-specific protease activity)|go:"GO:0035634"(response to stilbenoid)|go:"GO:0043231"(intracellular membrane-bounded organelle)|go:"GO:0050727"(regulation of inflammatory response)|go:"GO:0060339"(negative regulation of type I interferon-mediated signaling pathway)|interpro:IPR001394(Peptidase C19, ubiquitin carboxyl-terminal hydrolase 2)|interpro:IPR018200|interpro:IPR028889|interpro:IPR038765|rcsb pdb:5CHT|rcsb pdb:5CHV|reactome:R-MMU-1169408|reactome:R-MMU-5689880|reactome:R-MMU-912694	-	function:"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"|comment:mint|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	-	figure legend:f4b f4c f4e|comment:"The activity of USP18 was quantified by using a newly developed ISG15-based fluorescence  polarization (FP) assay reagent (Fig. 4A). The advantage of this reagent over conventional  ISG15-based reagents, such as ISG15-amidomethylcoumarin (ISG15-AMC), is the presence  of a native isopeptide linkage between the C-terminal Gly of ISG15 and a Lys side chain  resembling natural ISG15-linked substrates more closely [13]. The substrate was synthesized  from murine ISG15-C76S and TAMRA-(γ-thioK)-G peptide using the reported general  method for the synthesis of analogous Ub and Ub-like protein-based FP reagents [30].  Incubation of a fixed concentration of 100 nM of this substrate with different concentrations  of USP18 resulted in a dose-dependent decrease of the polarization value (in mP) indicating  proteolytic cleavage of the substrate (Fig. 4C)."|comment:"Using the assay described above, we determined the Michaelis-Menten kinetic parameters of  USP18 in a buffer with physiological pH and salt concentration. The parameters were  obtained by incubating different amounts of the substrate with a fixed concentration of USP18  (Fig. 4B). The measurements revealed a Km=4.6±0.2 μM, a Vmax=0.14±0.003 FM min-1, a  kcat=of 0.23±0.004 sec-1, and catalytic efficiency kcat/Km=5 104±2 104 M-1 sec-1 for USP18"|full coverage:Only protein-protein interactions|curation depth:imex curation	taxid:-1(in vitro)|taxid:-1(In vitro)	kcat:0.23(second -1)	2014/02/07	2014/10/16	rogid:rLwDq3/OLBVXU0U9MVyiTeULqog10090	rogid:O0NdHT+5B0FrZAHxFjPRBQv/6HY10090	intact-crc:914ADCCF48445E03|rigid:GiZOD3rFy7McSSX/+5on4TETPr0	false	-	-	-	-	psi-mi:"MI:0867"(tag visualisation by fluorescence)	psi-mi:"MI:0396"(predetermined participant)