#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:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0114"(x-ray crystallography) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691145|wwpdb:6xaa|imex:IM-28190-1 - - 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:Table 1|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/29 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:4JI0hhoEoVAmfKOyHyVoYLYpVV0 false modified glycine residue:75-75|sufficient binding region:1-75 sufficient binding region:746-1060 1 1 psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:P05161 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-746466|uniprotkb:Q7Z2G2|uniprotkb:Q96GF0|intact:EBI-1056284|uniprotkb:Q5SVA4|ensembl:ENSP00000496832 intact:EBI-25492388 psi-mi:isg15_human(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:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0114"(x-ray crystallography) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0407"(direct interaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691177|wwpdb:6xa9|imex:IM-28190-3 - - 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_005092.1|ensembl:ENSG00000187608(gene)|ensembl:ENST00000649529(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005737"(cytoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|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:IPR019956|interpro:IPR029071|mint:P05161|rcsb pdb:1Z2M|rcsb pdb:2HJ8|rcsb pdb:3PHX|rcsb pdb:3PSE|rcsb pdb:3R66|rcsb pdb:3RT3|rcsb pdb:3SDL|rcsb pdb:5TL6|rcsb pdb:5W8T|rcsb pdb:5W8U|rcsb pdb:6BI8|rcsb pdb:6FFA|rcsb pdb:6XA9|reactome:R-HSA-1169408|reactome:R-HSA-168276|reactome:R-HSA-168928|reactome:R-HSA-5656169|reactome:R-HSA-909733|reactome:R-HSA-936440|dip:DIP-29814N intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:Table 1|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/29 rogid:k01VuKv72XNTX3hhlIT4Lr0Xl849606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:sAbJ18A/aEiem/M8llIq8nKXmD4 false modified glycine residue:156-156|sufficient binding region:79-156 sufficient binding region:746-1060 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0435"(protease assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-25691704|imex:IM-28190-11 - - 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:Appendix Fig S1B, 2C, Figure 3D, 5 E/F, 6E|comment:Very high activity and striking Lys48-polyubiquitin specificity was observed for SARS2 PLpro.|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/30 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:4JI0hhoEoVAmfKOyHyVoYLYpVV0 false cross linker:48-48 mutation disrupting interaction rate:814-814|mutation decreasing interaction rate:911-912|mutation with no effect:901-901|mutation with no effect:916-916|mutation decreasing interaction rate:977-977|mutation decreasing interaction rate:970-970|sufficient binding region:746-1060 3 - psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) uniprotkb:P05161 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-746466|uniprotkb:Q7Z2G2|uniprotkb:Q96GF0|intact:EBI-1056284|uniprotkb:Q5SVA4|ensembl:ENSP00000496832 intact:EBI-25492388 psi-mi:isg15_human(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:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0435"(protease assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-25691730|imex:IM-28190-13 - - 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_005092.1|ensembl:ENSG00000187608(gene)|ensembl:ENST00000649529(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005737"(cytoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|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:IPR019956|interpro:IPR029071|mint:P05161|rcsb pdb:1Z2M|rcsb pdb:2HJ8|rcsb pdb:3PHX|rcsb pdb:3PSE|rcsb pdb:3R66|rcsb pdb:3RT3|rcsb pdb:3SDL|rcsb pdb:5TL6|rcsb pdb:5W8T|rcsb pdb:5W8U|rcsb pdb:6BI8|rcsb pdb:6FFA|rcsb pdb:6XA9|reactome:R-HSA-1169408|reactome:R-HSA-168276|reactome:R-HSA-168928|reactome:R-HSA-5656169|reactome:R-HSA-909733|reactome:R-HSA-936440|dip:DIP-29814N intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:Appendix Fig S1C, EV3-E/F,Figure 3F, Ext. Data 2C,5 E/F|comment:"The K232E (p.Lys977Glu) mutation (Ext. fig 5); it is unclear what the effect of this mutation is on proISG15 cleavage."|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/30 rogid:k01VuKv72XNTX3hhlIT4Lr0Xl849606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:sAbJ18A/aEiem/M8llIq8nKXmD4 false mutation:78-78|sufficient binding region:2-165|his tag:n-n mutation decreasing interaction rate:901-901|sufficient binding region:746-1060|mutation decreasing interaction rate:916-916|mutation decreasing interaction rate:911-912|mutation with no effect:977-977|mutation with no effect:970-970|mutation decreasing interaction rate:814-814 - - psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) uniprotkb:P05161 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-746466|uniprotkb:Q7Z2G2|uniprotkb:Q96GF0|intact:EBI-1056284|uniprotkb:Q5SVA4|ensembl:ENSP00000496832 intact:EBI-25492388 psi-mi:isg15_human(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:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0435"(protease assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0570"(protein cleavage) psi-mi:"MI:0469"(IntAct) intact:EBI-25691929|imex:IM-28190-15 - - 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_005092.1|ensembl:ENSG00000187608(gene)|ensembl:ENST00000649529(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005737"(cytoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|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:IPR019956|interpro:IPR029071|mint:P05161|rcsb pdb:1Z2M|rcsb pdb:2HJ8|rcsb pdb:3PHX|rcsb pdb:3PSE|rcsb pdb:3R66|rcsb pdb:3RT3|rcsb pdb:3SDL|rcsb pdb:5TL6|rcsb pdb:5W8T|rcsb pdb:5W8U|rcsb pdb:6BI8|rcsb pdb:6FFA|rcsb pdb:6XA9|reactome:R-HSA-1169408|reactome:R-HSA-168276|reactome:R-HSA-168928|reactome:R-HSA-5656169|reactome:R-HSA-909733|reactome:R-HSA-936440|dip:DIP-29814N intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:Appendix Fig S1D, Figure 3E, Ext. Data 2D,6D|comment:cleavage was less rapid with the Pro-CTD construct than the 2-165 construct.|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/30 rogid:k01VuKv72XNTX3hhlIT4Lr0Xl849606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:sAbJ18A/aEiem/M8llIq8nKXmD4 false mutation:78-78|sufficient binding region:79-165|his tag:n-n mutation decreasing interaction rate:814-814|sufficient binding region:746-1060 - - psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) psi-mi:"MI:0818"(molecular weight estimation by coomasie staining) uniprotkb:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691515|imex:IM-28190-5 - - 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:"(1D),Appendix Figure S1A, 2B, Ext.Data 2A"|kinetics:Kcat/Km =86/M/sec for WT;Y171R = 51/M/sec;N156E=62/M/sec|comment:"PLpro N156E (and, to a lesser degree, Y171R) resulted in selective decrease of activity in ISG15 cleavage assays, with little impact on ubiquitin cleavage."|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/30 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:4JI0hhoEoVAmfKOyHyVoYLYpVV0 false tetramethyl rhodamine label:?-? mutation decreasing interaction rate:901-901|sufficient binding region:746-1060|mutation decreasing interaction rate:916-916 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:Q64339 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-8345781|uniprotkb:Q8K0H3|intact:MINT-4139466|ensembl:ENSMUSP00000082548 intact:EBI-25492388 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:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:10090(mouse)|taxid:10090(Mus musculus) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691525|imex:IM-28190-7 - - 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 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - 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 chain-seq-start:819|chain-seq-end:2763 figure legend:"(1D),Appendix Figure S1A, 2B, 3C, Ext.Data 2A, 6C"|kinetics:Kcat/Km =30210 /M/sec WT; N156E=4803/M/sec;Y171R=8399 /M/sec;Arg166Ser/Glu167Arg =4336/M/sec;F69S=11690/M/sec.|comment:SARS2 PLpro hydrolysed an ISG15-TAMRA fluorescent substrate 350-fold more efficiently as compared to ubiquitin-TAMRA.|comment:"PLpro N156E (and, to a lesser degree, Y171R) resulted in selective decrease of activity in ISG15 cleavage assays, with little impact on ubiquitin cleavage."|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/29 rogid:rLwDq3/OLBVXU0U9MVyiTeULqog10090 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:mfpKiuCaISm+UZ69yteAmRckTBo false tetramethyl rhodamine label:c-c|sufficient binding region:1-154|mutation:76-76,144-144 mutation decreasing interaction rate:901-901|mutation decreasing interaction rate:916-916|mutation decreasing interaction rate:911-912|sufficient binding region:746-1060|mutation decreasing interaction rate:814-814 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:P05161 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-746466|uniprotkb:Q7Z2G2|uniprotkb:Q96GF0|intact:EBI-1056284|uniprotkb:Q5SVA4|ensembl:ENSP00000496832 intact:EBI-25492388 psi-mi:isg15_human(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:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691550|imex:IM-28190-9 - - 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_005092.1|ensembl:ENSG00000187608(gene)|ensembl:ENST00000649529(transcript)|go:"GO:0005178"(integrin binding)|go:"GO:0005576"(extracellular region)|go:"GO:0005634"(nucleus)|go:"GO:0005654"(nucleoplasm)|go:"GO:0005737"(cytoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0007229"(integrin-mediated signaling pathway)|go:"GO:0009615"(response to virus)|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:IPR019956|interpro:IPR029071|mint:P05161|rcsb pdb:1Z2M|rcsb pdb:2HJ8|rcsb pdb:3PHX|rcsb pdb:3PSE|rcsb pdb:3R66|rcsb pdb:3RT3|rcsb pdb:3SDL|rcsb pdb:5TL6|rcsb pdb:5W8T|rcsb pdb:5W8U|rcsb pdb:6BI8|rcsb pdb:6FFA|rcsb pdb:6XA9|reactome:R-HSA-1169408|reactome:R-HSA-168276|reactome:R-HSA-168928|reactome:R-HSA-5656169|reactome:R-HSA-909733|reactome:R-HSA-936440|dip:DIP-29814N intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:"(1D),Appendix Figure S1A, Ext.Data 2A"|kinetics:Kcat/Km =14040 /M/sec.|comment:"A substrate comprising only the C-terminal ubiquitin-like fold of ISG15, (ISG15 CTD -TAMRA) was still cleaved with 160-fold higher efficiency compared to ubiquitin."|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/06/29 rogid:k01VuKv72XNTX3hhlIT4Lr0Xl849606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:sAbJ18A/aEiem/M8llIq8nKXmD4 false sufficient binding region:79-156|tetramethyl rhodamine label:?-? sufficient binding region:746-1060 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25820898|imex:IM-28190-20 - - 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:"(1D),Appendix Figure S1A, figure 3C"|kinetics:KG‐TAMRA peptide was hydrolysed 19‐fold faster - Kcat/Km=1,634/M/sec, when linked to a non‐cleavable Lys48‐diubiquitin. PLpro F69S Kcat/Km=45/M/Sec|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) - 2020/06/24 2020/09/01 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:4JI0hhoEoVAmfKOyHyVoYLYpVV0 false tetramethyl rhodamine label:?-? mutation decreasing interaction rate:901-901|sufficient binding region:746-1060|mutation decreasing interaction rate:916-916|mutation disrupting interaction rate:814-814 2 - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25691987|imex:IM-28190-17 - - 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:4B, EV4|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) ic50:0.81x10^-6(molar) 2020/06/24 2020/06/30 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 rigid:4JI0hhoEoVAmfKOyHyVoYLYpVV0 false tetramethyl rhodamine label:c-c sufficient binding region:746-1060 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) uniprotkb:J3QS39 uniprotkb:P0DTD1-PRO_0000449621 intact:EBI-25691162|ensembl:ENSP00000464510 intact:EBI-25492388 psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:p0dtd1-pro_0000449621(display_long)|uniprotkb:rep(gene name)|psi-mi:rep(display_short)|uniprotkb:ORF1ab polyprotein(gene name synonym)|uniprotkb:1a-1b(orf name) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:2697049(SARS-CoV-2)|taxid:2697049(SARS-CoV-2) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25692004|imex:IM-28190-19 - psi-mi:"MI:1060"(spoke expansion) 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) ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 intact:EBI-25492095(chain-parent)|uniprotkb:P0DTD1(chain-parent) - - chain-seq-start:819|chain-seq-end:2763 figure legend:4B, 5C|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) ic50:0.81x10^-6(molar) 2020/06/24 2020/06/30 rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 rogid:edNmSGWH7aKPoOZtWjGjL1M0aK42697049 - false tetramethyl rhodamine label:c-c sufficient binding region:746-1060 - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant) chebi:"CHEBI:156041" uniprotkb:J3QS39 intact:EBI-25692013 intact:EBI-25691162|ensembl:ENSP00000464510 psi-mi:rac5c(display_short)|psi-mi:"CHEBI:156041"(display_long) psi-mi:j3qs39_human(display_long)|uniprotkb:UBB(gene name)|psi-mi:UBB(display_short) psi-mi:"MI:0990"(cleavage assay) Klemm et al. (2020) imex:IM-28190|pubmed:32845033 taxid:-2(chemical synthesis)|taxid:-2("Chemical synthesis (Chemical synthesis)") taxid:9606(human)|taxid:9606(Homo sapiens) psi-mi:"MI:0194"(cleavage reaction) psi-mi:"MI:0469"(IntAct) intact:EBI-25692004|imex:IM-28190-19 - psi-mi:"MI:1060"(spoke expansion) psi-mi:"MI:0586"(inhibitor) psi-mi:"MI:0502"(enzyme target) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0497"(neutral component) psi-mi:"MI:0328"(small molecule) psi-mi:"MI:0326"(protein) - ensembl:ENSG00000170315(gene)|ensembl:ENST00000578706(transcript)|interpro:IPR000626(Ubiquitin)|interpro:IPR019954|interpro:IPR019956|interpro:IPR029071|rcsb pdb:6NJ9|rcsb pdb:6NOG|rcsb pdb:6XQC|rcsb pdb:7BBD|rcsb pdb:7BU0 - - - figure legend:4B, 5C|dataset:Coronavirus - Interactions investigated in the context of Coronavirus|dataset:Virus - Publications including interactions involving viral proteins|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:-1(in vitro)|taxid:-1(In vitro) ic50:0.81x10^-6(molar) 2020/06/24 2020/06/30 - rogid:i4v/hqty6KDy/B1ALYsfEjF7CGY9606 - false - tetramethyl rhodamine label:c-c - - psi-mi:"MI:0396"(predetermined participant) psi-mi:"MI:0396"(predetermined participant)