IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ http://www.ebi.ac.uk/ freitas-2020-3 in vitro In vitro protease assay protease assay weight identificat confirmation by molecular weight weight identificat Freitas BT., Durie IA., Murray J., Longo JE., Miller HC., Crich D., Hogan RJ., Tripp RA., Pegan SD. Virus - Publications including interactions involving viral proteins The catalytic core of SARS-CoV-2 PLpro (orf1ab 1564-1876) is stated to be 315 aa in methods, but aas 1564-1876 is only 313 residues. Trihalo compounds in Mini-PROTEAN TGX Stain-Free Gels react with tryptophan residues in proteins in a UV-induced 1-minute reaction to produce fluorescence. spegan@uga.edu,scott.d.pegan.mil@mail.mil ACS infectious diseases 2020 Only protein-protein interactions imex curation imex curation Coronavirus - Interactions investigated in the context of Coronavirus freitas-2020-1 in vitro In vitro cleavage cleavage assay cleavage predetermined predetermined participant predetermined Freitas BT., Durie IA., Murray J., Longo JE., Miller HC., Crich D., Hogan RJ., Tripp RA., Pegan SD. Virus - Publications including interactions involving viral proteins The catalytic core of SARS-CoV-2 PLpro (orf1ab 1564-1876) is stated to be 315 aa in methods, but aas 1564-1876 is only 313 residues. The increase in AMC fluorescence was observed after the cleavage of AMC from Ub-AMC and ISG15-AMC. spegan@uga.edu,scott.d.pegan.mil@mail.mil ACS infectious diseases 2020 Only protein-protein interactions imex curation imex curation Coronavirus - Interactions investigated in the context of Coronavirus freitas-2020-2 in vitro In vitro deubiquitinase assay deubiquitinase assay deubiquitinase assay weight by comassie molecular weight estimation by coomasie staining weight by comassie Freitas BT., Durie IA., Murray J., Longo JE., Miller HC., Crich D., Hogan RJ., Tripp RA., Pegan SD. Virus - Publications including interactions involving viral proteins The catalytic core of SARS-CoV-2 PLpro (orf1ab 1564-1876) is stated to be 315 aa in methods, but aas 1564-1876 is only 313 residues. spegan@uga.edu,scott.d.pegan.mil@mail.mil ACS infectious diseases 2020 Only protein-protein interactions imex curation imex curation Coronavirus - Interactions investigated in the context of Coronavirus p0dtd1-pro_0000449621 Papain-like protease nsp3 rep ORF1ab polyprotein 1a-1b protein protein SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 2019-nCoV APTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTEVNEFACVVADAVIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPPDEDEEEGDCEEEEFEPSTQYEYGTEDDYQGKPLEFGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIEVNSFSGYLKLTDNVYIKNADIVEEAKKVKPTVVVNAANVYLKHGGGVAGALNKATNNAMQVESDDYIATNGPLKVGGSCVLSGHNLAKHCLHVVGPNVNKGEDIQLLKSAYENFNQHEVLLAPLLSAGIFGADPIHSLRVCVDTVRTNVYLAVFDKNLYDKLVSSFLEMKSEKQVEQKIAEIPKEEVKPFITESKPSVEQRKQDDKKIKACVEEVTTTLEETKFLTENLLLYIDINGNLHPDSATLVSDIDITFLKKDAPYIVGDVVQEGVLTAVVIPTKKAGGTTEMLAKALRKVPTDNYITTYPGQGLNGYTVEEAKTVLKKCKSAFYILPSIISNEKQEILGTVSWNLREMLAHAEETRKLMPVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTTVASLINTLNDLNETLVTMPLGYVTHGLNLEEAARYMRSLKVPATVSVSSPDAVTAYNGYLTSSSKTPEEHFIETISLAGSYKDWSYSGQSTQLGIEFLKRGDKSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDNINLHTQVVDMSMTYGQQFGPTYLDGADVTKIKPHNSHEGKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQIELKFNPPALQDAYYRARAGEAANFCALILAYCNKTVGELGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGVQIPCTCGKQATKYLVQQESPFVMMSAPPAQYELKHGTFTCASEYTGNYQCGHYKHITSKETLYCIDGALLTKSSEYKGPITDVFYKENSYTTTIKPVTYKLDGVVCTEIDPKLDNYYKKDNSYFTEQPIDLVPNQPYPNASFDNFKFVCDNIKFADDLNQLTGYKKPASRELKVTFFPDLNGDVVAIDYKHYTPSFKKGAKLLHKPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGMDNLACEDLKPVSEEVVENPTIQKDVLECNVKTTEVVGDIILKPANNSLKITEEVGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYMPYFFTLLLQLCTFTRSTNSRIKASMPTTIAKNTVKSVGKFCLEASFNYLKSPNFSKLINIIIWFLLLSVCLGSLIYSTAALGVLMSNLGMPSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSGLDSLDTYPSLETIQITISSFKWDLTAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVHFISNSWLMWLIINLVQMAPISAMVRMYIFFASFYYVWKSYVHVVDGCNSSTCMMCYKRNRATRVECTTIVNGVRRSFYVYANGGKGFCKLHNWNCVNCDTFCAGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVTVKNGSIHLYFDKAGQKTYERHSLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCEESSAKSASVYYSQLMCQPILLLDQALVSDVGDSAEVAVKMFDAYVNTFSSTFNVPMEKLKTLVATAEAELAKNVSLDNVLSTFISAARQGFVDSDVETKDVVECLKLSHQSDIEVTGDSCNNYMLTYNKVENMTPRDLGACIDCSARHINAQVAKSHNIALIWNVKDFMSLSEQLRKQIRSAAKKNNLPFKLTCATTRQVVNVVTTKIALKGG 819 2763 isg15_human Ubiquitin-like protein ISG15 ISG15 G1P2 UCRP Interferon-induced 15 kDa protein Interferon-induced 17 kDa protein Ubiquitin cross-reactive protein protein protein human Homo sapiens Human MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPLASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDDLFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS isg15_bovin Ubiquitin-like protein ISG15 Interferon-stimulated gene product 17 Ubiquitin cross-reactive protein ISG15 G1P2 ISG17 UCRP protein protein bovin Bos taurus (Bovine) Bovine MGGDLTVKMLGGQEILVPLRDSMTVSELKQFIAQKINVPAFQQRLAHLDSREVLQEGVPLVLQGLRAGSTVLLVVQNCISILVRNDKGRSSPYEVQLKQTVAELKQQVCQKERVQADQFWLSFEGRPMDDEHPLEEYGLMKGCTVFMNLRLRGG isg15_mouse Ubiquitin-like protein ISG15 Isg15 G1p2 Ucrp Interferon-induced 15 kDa protein Interferon-induced 17 kDa protein Ubiquitin cross-reactive protein protein protein mouse Mus musculus Mouse MAWDLKVKMLGGNDFLVSVTNSMTVSELKKQIAQKIGVPAFQQRLAHQTAVLQDGLTLSSLGLGPSSTVMLVVQNCSEPLSILVRNERGHSNIYEVFLTQTVDTLKKKVSQREQVHEDQFWLSFEGRPMEDKELLGEYGLKPQCTVIKHLRLRGGGGDQCA 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 mint 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 b2lug8_pig protein protein pig Sus scrofa (Pig) Pig MGRELKVKMLGGKEILVPLRDCMMASDLKQQIAREIGVPAFQQRLAHPAGNVLQDGVPLVNQGLGPGSMVLLMVQSFRDPLSILVRNDKGRSNAYEVWLTQTVAELKQQVCQLEGVQADHFWLTFEGKPMEDEHQLGEYDLKPMCTVYMNLRLRGGGTGPGEHLTEC a0a5n4dax7_camdr Cadr_000013024 protein protein camdr Camelus dromedarius Arabian camel MGGILKVKMLEGREIQVTLRDSMLLSELKQQIAQKIHVPTFQQRLAHPESQQVLKDGEPLVRQGLKPGDTVLLMVQNCEDPLSILVRNDKGRSSAYEVWLTQTVAELKRQVCQKEHAQADQFWLTFEGKPMEDQHQLGEYGLTARCTVYMNLRLRGGGAGPGGR q9gkp4_sheep ISG17 protein protein sheep Ovis aries (Sheep) Sheep MGGDLKVKMLGGEEILVPLRDSMMVSELKQFIAQKINVPAFQQRLAHLDSREVLQEGVPLVHQGLKAGSTILLMVQNCSATLNILVRNDKGRSSSYEVQLTQTVAVLKQQVCQRERVQADQFWLSFEGKPMDDEHPLGEYGLTTGCTVFMNLRLRGG l5lc70_myods MDA_GLEAN10007532 protein protein David's myotis Myotis davidii MLSNEFQVPMRDSMLLSELKQLITQKIQVPAFRQRLLVQGSNEVLQDGVPLAHQGLRSGSEVVLVVQSCDRPLSILVRNDRGNNRAYEVQLTQKVARLKEQVAERESTNVDQFWLSFQGQPLDDEKQLGEYDLTPHCTVQMNLRLRGGEEGLGGQR isg15_rouae ISG15_ROUAE protein protein rouae Rousettus aegyptiacus a0a1s2zwt3_erieu ISG15 protein protein Western European hedgehog Erinaceus europaeus MGRTLTVKMMTGQSFEVPLTESMQLQELRQLLAQLTSVPAFQQRLILKENGKSRVLEDGPSLSSQGVQPNSMVVLVVEDCKGSLSILVRNDKGRSSLYEVRLTQKVAELKQQVSCQEHVPTDQFWLSFQGRPLEDQQLLGEYSLTSHSTVYMNLYLRGGQDHMP r9qb93_tupbe protein protein Common tree shrew Tupaia belangeri Tupaia glis belangeri MGRDLKVKMLGGQEFMVPISDSMLAMELKQKITKKIGVPAFQQRLAIHPSGTVLQDRVPLGHQGLDSDSIVLLVVQSCDSPLNILVRNNKGRSSSYEVRLTQTVAHLKQLVSQQEGVQADLFWLSYEGRDMEDQKPLGEYGLMSQSTVYMHLRLRGG ubiq_human UBIQ_HUMAN protein protein human Homo sapiens Human MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG rlrgg RLRGG peptide peptide polypeptide oligopeptide oligopeptide polypeptide chemical synthesis Chemical synthesis (Chemical synthesis) grl-0617 GRL-0617 small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) compound 6 5-N-Acetylamino-2-methyl-N-[(R)-1-(1-naphthyl)ethyl]benzamide small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) q6tfz7_9viru Replicase Transcriptase protein protein Crimean-Congo hemorrhagic fever orthonairovirus Crimean-Congo hemorrhagic fever orthonairovirus MDFLRSLDWTQVIAGQYVSNPRFNISDYFEIVRQPGDGNCFYHSIAELTMPNKTDHSYHYIKRLTESAARKYYQEEPEARLVGLSLEDYLKRMLSDNEWGSTLEASMLAKEMGITIIIWTVAASDEVEAGIKFGDGDVFTAVNLLHSGQTHFDALRILPQFETDTREALSLMDRVIAVDQLTSSSSDELQDYEDLALALTSAEESNRRSSLDEVTLSKKQAEILRQKASQLSKLVNKSQNIPTRVGRVLDCMFNCKLCVEISADTLILRPESKEKIGEIMSLRQLGHKLLTRDKQIKQEFSRMKLYVTKDLLDHLDVGGLLRAAFPGTGIERHMQLLHSEMILDICTVSLGVMLSTFLYGSNNKNKKKFITNCLLSTALSGKKVYKVLGNLGNELLYKAPRKALATVCSALFGKQINKLQNCFRTISPVSLLALRNLDFDCLSVQDYNGMIENMSKLDNTDVEFNHREIADLNQLTSRLITLRKEKDTDLLKQWFPESDLTRRSIRNAANAEEFVISEFFKKKDIMKFISTSGRAMSAGKIGNVLSYAHNLYLSKSSLNMTSEDISQLLIEIKRLYALQEDSEVEPIAIICDGIESNMKQLFAILPPDCARECEVLFDDIRNSPTHSTAWKHALRLKGTAYEGLFANCYGWQYIPEDIKPSLTMLIQTLFPDKFEDFLDRTQLHPEFRDLTPDFSLTQKVHFKRNQIPSVENVQISIDATLPESVEAVPVTERKMFPLPETPLSEVHSIERIMENFTRLMHGGRLSTKKRDGDPAEQGNQQSITEHESSSISAFKDYGERGIVEENHMKFSGEDQLETRQLLLVEVGFQTDIDGKIRTDHKKWKDILKLLELLGIKCSFIACADCSSTPPDRWWITEDRVRVLKNSVSFLFNKLSRNSPTEVTDIVVGAISTQKVRSYLKAGTATKTPVSTKDVLETWEKMKEHILNRPTGLTLPTSLEQAMRKGLVEGVVISKEGSESCINMLKENLDRITDEFERTKFKHELTQNITTSEKMLLSWLSEDIKSSRCGECLSNIKKAVDETANLSEKIELLAYNLQLTNHCSNCHPNGVNISNTSNVCKRCPKIEVVSHCENKGFEDSNECLTDLDRLVRLTLPGKTEKERRVKRNVEYLIKLMMSMSGIDCIKYPTGQLITHGRVSAKHNDGNLKDRSDDDQRLAEKIDTVRKELSESKLKDYSTYARGVISNSLKNLSRQGKSKCSVPRSWLEKVLFDLKVPTKDEEVLINIRNSLKARSEFVRNNDKLLIRSKEELKKCFDVQSFKLKKNKQPVPFQVDCILFKEVAAECMKRYIGTPYEGIVDTLVSLINVLTRFTWFQEVVLYGKICETFLRCCTEFNRSGVKLVKIRHCNINLSVKLPSNKKENMLCCLYSGNMELLQGPFYLNRRQAVLGSSYLYIVITLYIQVLQQYRCLEVINSVSEKTLQDIENHSMTLLEDSFREITFALEGRFEESYKIRTSRCRASGNFLNRSSRDHFISVVSGLNLVYGFLIKDNLLANSQQQNKQLQMLRFGMLAGLSRLVCPNELGKKFSTSCRRIEDNIARLYLQTSIYCSVRDVEDNVKHWKQRDLCPEVTIPCFTVYGTFVNSDRQLIFDIYNVHIYNKEMDNFDEGCISVLEETAERHMLWELDLMNSLCSDEKKDTRTARLLLGCPNVRKAANREGKKLLKLNSDTSTDTQSIASEVSDRRSYSSSKSRIRSIFGRYNSQKKPFELRSGLEVFNDPFNDYQQAITDICQFSEYTPNKESILKDCLQIIRKNPSHTMGSFELIQAISEFGMSKFPPENIDKARRDPKNWVSISEVTETTSIVASPRTHMMLKDCFKIILGTENKKIVKMLRGKLKKLGAISTNIEIGKRDCLDLLSTVDGLTDQQKENIVNGIFEPSKLSFYHWKELVKKNIDEVLLTEDGNLIFCWLKTISSSVKGSLKKRLKFMNIHSPELMPENCLFSSEEFNELIKLKKLLLNEQQDEQELKQDLLISSWIKCITACKDFASINDKIQKFIYHLSEELYDIRLQHLELSKLKQEHPSVSFTKEEVLIKRLEKNFLKQHNLEIMETVNLVFFAALSAPWCLHYKALESYLVRHPEILDCGSKEDCKLTLLDLSVSKLLVCLYQKDDEELINSSSLKLGFLVKYVVTLFTSNGEPFSLSLNDGGLDLDLHKTTDEKLLHQTKIVFAKIGLSGNSYDFIWTTQMIANSNFNVCKRLTGRSTGERLPRSVRSKVIYEMVKLVGETGMAILQQLAFAQALNYEHRFYAVLAPKAQLGGARDLLVQETGTKVMHATTEMFSRNLLKTTSDDGLTNPHLKETILNVGLDCLANMRNLDGKPISEGSNLVNFYKVICISGDNTKWGPIHCCSFFSGMMQQVLKNVPDWCSFYKLTFIKNLCRQVEIPAGSIKKILNVLRYRLCSKGGVEQHSEEDLRRLLTDNLDSWDGNDTVKFLVTTYISKGLMALNSYNHMGQGIHHATSSVLTSLAAVLFEELAIFYLKRSLPQTTVHVEHAGSSDDYAKCIVVTGILSKELYSQYDETFWKHACRLKNFTAAVQRCCQMKDSAKTLVSDCFLEFYSEFMMGYRVTPAVIKFMFTGLINSSVTSPQSLMQACQVSSQQAMYNSVPLVTNTAFTLLRQQIFFNHVEDFIRRYGILTLGTLSPFGRLFVPTYSGLASSTVALEDAEVIARAAQTLQMNSVSIQSSSLTTLDSLGRSRTSSTAEDSSSVSDTTAASHDSGSSSSSFSFELNRPLSETELQFIKALSSLKSTQACEVIQNRITGLYCNSNEGPLDRHNVIYSSRMADSCDWLKDGKRRGNLELANRIQSVLCILIAGYYRSFGGEGTEKQVKASLNRDDNKIIEDPMIQLIPEKLRRELERLGVSRMEVDELMPSISPDDTLAQLVAKKLISLNVSTEEYSAEVSRLKQTLTARNVLHGLAGGIKELSLPIYTIFMKSYFFKDNVFLSLTDRWSTKHSTNYRDSCGKQLKGRIITKYTHWLDTFLGCSVSINRHTTVKEPSLFNPNIRCVNLITFEDGLRELSVIQSHLKVFENEFTNLNLQFSDPNRQKLRIVESRPAESELEANRAVIVKTKLFSATEQVRLSNNPAVVMGYLLDESAISEVKPTKVDFSNLLKDRFKIMQFFPSVFTLIKMLTDESSDSEKSGLSPDLQQVARYSNHLTLLSRMIQQAKPTVTVFYMLKGNLMNTEPTVAELVSYGIKEGRFFRLSDTGVDASTYSVKYWKILHCISAIGCLPLSQADKSSLLMSFLNWRVNMDIRTSDCPLSSHEASILSEFDGQVIANILASELSSVKRDSEREGLTDLLDYLNSPTELLKKKPYLGTTCKFNTWGDSNRSGKFTYSSRSGESIGIFIAGKLHIHLSSESVALLCETERQVLSWMSKRRTEVITKEQHQLFLSLLPQSHECLQKHKDGSALSVIPDSSNPRLLKFVPLKKGLAVVKIKKQILTVKKQVVFDAESEPRLQWGHGCLSIVYDETDTQTTYHENLLKVKHLVDCSTDRKKLLPQSVFSDSKVVLSRIKFKTELLLNSLTLLHCFLKHAPSDAIMEVESKSSLLHKYLKSGGVRQRNTEVLFREKLNKVVIKDNLEQGVEEEIEFCNNLTKTVSENPLPLSCWSEVQNYIEDIGFNNVLVNIDRNTVKSELLWKFTLDTNVSTTSTIKDVRTLVSYVSTETIPKFLLAFLLYEEVLMNLINQCKAVKELINSTGLSDLELESLLTLCAFYFQSECSKRDGPRCSFAALLSLIHEDWQRIGKNILVRANNELGDVSLKVNIVLVPLKDMSKPKSERVVMARRSLNHALSLMFLDEMSLPELKSLSVNCKMGNFEGQECFEFTILKDNSARLDYNKLIDHCVDMEKKREAVRAVEDLILMLTGRAVKPSAVTQFVHGDEQCQEQISLDDLMANDTVTDFPDREAEALKTGNLGFNWDSD isg15-rep-19 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966187 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -human Moderate enzymatic activity -"pale green" result isg15-rep-20 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966188 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -cow Moderate enzymatic activity -"pale green" result isg15-rep-21 3966183 N/A 3966189 enzyme target enzyme target substrate substrate neutral component neutral component purified purified N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) cleavage cleavage reaction cleavage false false false Figure 4 -mouse Moderate enzymatic activity -"pale green" result isg15-rep-22 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966190 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -pig Moderate enzymatic activity -"pale green" result b2lug8_pig-rep-1 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966191 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -camel Moderate enzymatic activity -"pale green" result isg17-rep-1 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966192 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -sheep High enzymatic activity -"dark green" result The stated accession number is for sheep ISG17 (AF152103.1), rather than ISG15: the sequence of the AF152103.1 (Uniprot Q9GKP4) protein has 100% homology to Sheep ISG15- Uniprot A0A6P9FNA5, and 99.4% with the longer protein W5PBE1. l5lc70_myods-rep-1 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966193 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -vesper bat High enzymatic activity -"dark green" result isg15_rouae-rep-1 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966194 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -Egyptian fruit bat Low enzymatic activity -"orange" result isg15-rep-23 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966195 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -Hedgehog Low enzymatic activity -"orange" result r9qb93_tupbe-rep-1 3966183 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966196 enzyme target enzyme target substrate substrate neutral component neutral component purified purified cleavage cleavage reaction cleavage false false false Figure 4 -Northern tree Shrew Low enzymatic activity -"orange" result rep-ubiq_human-1 3966184 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966197 enzyme target enzyme target substrate substrate neutral component neutral component purified purified C-terminus coumarin label coumarin label c-term range C-terminal range c-term range c-term range C-terminal range c-term range false ecoli Escherichia coli (strain K12) cleavage cleavage reaction cleavage false false false 3966184 3966184 3966184 Table 1, figure S2 kcat/Km (uM-1 min-1) 10.3 isg15-rep-18 3966184 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966187 enzyme target enzyme target substrate substrate neutral component neutral component purified purified C-terminus coumarin label coumarin label c-term range C-terminal range c-term range c-term range C-terminal range c-term range false ecoli Escherichia coli (strain K12) cleavage cleavage reaction cleavage false false false 3966184 3966184 3966184 Table 1, figure S2 kcat/Km (uM-1 min-1) 10.3 rep-rlrgg-1 3966184 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966198 enzyme target enzyme target substrate substrate neutral component neutral component purified purified C-terminus coumarin label coumarin label c-term range C-terminal range c-term range c-term range C-terminal range c-term range false benzyloxycarbonyl modarg modified L-arginine residue ModArg n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) cleavage cleavage reaction cleavage false false false 3966184 Table 1 kcat/Km (uM-1 min-1) 0.0051 rep-rlrgg-2 3966184 N/A 3966199 inhibitor inhibitor neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966198 enzyme target enzyme target substrate substrate neutral component neutral component purified purified C-terminus coumarin label coumarin label c-term range C-terminal range c-term range c-term range C-terminal range c-term range false benzyloxycarbonyl modarg modified L-arginine residue ModArg n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) cleavage cleavage reaction cleavage false false false 3966184 3966184 Figure 5 grl_0617-rep-3 3966184 N/A 3966200 inhibitor inhibitor neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966198 enzyme target enzyme target substrate substrate neutral component neutral component purified purified C-terminus coumarin label coumarin label c-term range C-terminal range c-term range c-term range C-terminal range c-term range false benzyloxycarbonyl modarg modified L-arginine residue ModArg n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) cleavage cleavage reaction cleavage false false false 3966184 3966184 Figure 5 rep-ubiq_human-2 3966185 N/A 3966186 enzyme enzyme neutral component neutral component purified purified catalytic domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) N/A 3966197 enzyme target enzyme target substrate substrate neutral component neutral component purified purified Lys48 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false Gly76 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 4.0 deubiquitination deubiquitination reaction deubiquitination false false false Figure 3 q6tfz7_9viru-ubiq_human-1 3966185 N/A 3966197 enzyme target enzyme target substrate substrate neutral component neutral component purified purified Lys63 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false Gly76 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false Lys48 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false Lys11 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false Lys6 cross linker cross linker crosslinker crosslinker certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 2.0 N/A 3966201 enzyme enzyme neutral component neutral component purified purified Ovarian Tumour Domain (OTU) sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) deubiquitination deubiquitination reaction deubiquitination false false false Supp. Figure 3B positive control