| IED ID | IndEnz0002013861 |
| Enzyme Type ID | protease013861 |
| Protein Name |
Replicase polyprotein 1ab pp1ab ORF1ab polyprotein Cleaved into: Host translation inhibitor nsp1 Leader protein Non-structural protein 1 nsp1 ; Non-structural protein 2 nsp2 p65 homolog ; Papain-like protease nsp3 EC 3.4.19.12 EC 3.4.22.- Non-structural protein 3 nsp3 PL2-PRO Papain-like proteinase PL-PRO ; Non-structural protein 4 nsp4 ; 3C-like proteinase nsp5 3CL-PRO 3CLp EC 3.4.22.69 Main protease Mpro Non-structural protein 5 nsp5 SARS coronavirus main proteinase ; Non-structural protein 6 nsp6 ; Non-structural protein 7 nsp7 ; Non-structural protein 8 nsp8 ; Non-structural protein 9 nsp9 ; Non-structural protein 10 nsp10 Growth factor-like peptide GFL ; RNA-directed RNA polymerase nsp12 Pol RdRp EC 2.7.7.48 Non-structural protein 12 nsp12 ; Helicase nsp13 Hel EC 3.6.4.12 EC 3.6.4.13 Non-structural protein 13 nsp13 ; Proofreading exoribonuclease nsp14 ExoN EC 3.1.13.- Guanine-N7 methyltransferase Non-structural protein 14 nsp14 ; Uridylate-specific endoribonuclease nsp15 EC 4.6.1.- NendoU Non-structural protein 15 nsp15 ; 2'-O-methyltransferase nsp16 EC 2.1.1.57 Non-structural protein 16 nsp16 |
| Gene Name | rep 1a-1b |
| Organism | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Betacoronavirus Sarbecovirus Severe acute respiratory syndrome coronavirus (SARS-CoV) Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2) |
| Enzyme Sequence | MESLVPGFNEKTHVQLSLPVLQVRDVLVRGFGDSVEEVLSEARQHLKDGTCGLVEVEKGVLPQLEQPYVFIKRSDARTAPHGHVMVELVAELEGIQYGRSGETLGVLVPHVGEIPVAYRKVLLRKNGNKGAGGHSYGADLKSFDLGDELGTDPYEDFQENWNTKHSSGVTRELMRELNGGAYTRYVDNNFCGPDGYPLECIKDLLARAGKASCTLSEQLDFIDTKRGVYCCREHEHEIAWYTERSEKSYELQTPFEIKLAKKFDTFNGECPNFVFPLNSIIKTIQPRVEKKKLDGFMGRIRSVYPVASPNECNQMCLSTLMKCDHCGETSWQTGDFVKATCEFCGTENLTKEGATTCGYLPQNAVVKIYCPACHNSEVGPEHSLAEYHNESGLKTILRKGGRTIAFGGCVFSYVGCHNKCAYWVPRASANIGCNHTGVVGEGSEGLNDNLLEILQKEKVNINIVGDFKLNEEIAIILASFSASTSAFVETVKGLDYKAFKQIVESCGNFKVTKGKAKKGAWNIGEQKSILSPLYAFASEAARVVRSIFSRTLETAQNSVRVLQKAAITILDGISQYSLRLIDAMMFTSDLATNNLVVMAYITGGVVQLTSQWLTNIFGTVYEKLKPVLDWLEEKFKEGVEFLRDGWEIVKFISTCACEIVGGQIVTCAKEIKESVQTFFKLVNKFLALCADSIIIGGAKLKALNLGETFVTHSKGLYRKCVKSREETGLLMPLKAPKEIIFLEGETLPTEVLTEEVVLKTGDLQPLEQPTSEAVEAPLVGTPVCINGLMLLEIKDTEKYCALAPNMMVTNNTFTLKGGAPTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTEVNEFACVVADAVIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPPDEDEEEGDCEEEEFEPSTQYEYGTEDDYQGKPLEFGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIEVNSFSGYLKLTDNVYIKNADIVEEAKKVKPTVVVNAANVYLKHGGGVAGALNKATNNAMQVESDDYIATNGPLKVGGSCVLSGHNLAKHCLHVVGPNVNKGEDIQLLKSAYENFNQHEVLLAPLLSAGIFGADPIHSLRVCVDTVRTNVYLAVFDKNLYDKLVSSFLEMKSEKQVEQKIAEIPKEEVKPFITESKPSVEQRKQDDKKIKACVEEVTTTLEETKFLTENLLLYIDINGNLHPDSATLVSDIDITFLKKDAPYIVGDVVQEGVLTAVVIPTKKAGGTTEMLAKALRKVPTDNYITTYPGQGLNGYTVEEAKTVLKKCKSAFYILPSIISNEKQEILGTVSWNLREMLAHAEETRKLMPVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTTVASLINTLNDLNETLVTMPLGYVTHGLNLEEAARYMRSLKVPATVSVSSPDAVTAYNGYLTSSSKTPEEHFIETISLAGSYKDWSYSGQSTQLGIEFLKRGDKSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDNINLHTQVVDMSMTYGQQFGPTYLDGADVTKIKPHNSHEGKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQIELKFNPPALQDAYYRARAGEAANFCALILAYCNKTVGELGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGVQIPCTCGKQATKYLVQQESPFVMMSAPPAQYELKHGTFTCASEYTGNYQCGHYKHITSKETLYCIDGALLTKSSEYKGPITDVFYKENSYTTTIKPVTYKLDGVVCTEIDPKLDNYYKKDNSYFTEQPIDLVPNQPYPNASFDNFKFVCDNIKFADDLNQLTGYKKPASRELKVTFFPDLNGDVVAIDYKHYTPSFKKGAKLLHKPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGMDNLACEDLKPVSEEVVENPTIQKDVLECNVKTTEVVGDIILKPANNSLKITEEVGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYMPYFFTLLLQLCTFTRSTNSRIKASMPTTIAKNTVKSVGKFCLEASFNYLKSPNFSKLINIIIWFLLLSVCLGSLIYSTAALGVLMSNLGMPSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSGLDSLDTYPSLETIQITISSFKWDLTAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVHFISNSWLMWLIINLVQMAPISAMVRMYIFFASFYYVWKSYVHVVDGCNSSTCMMCYKRNRATRVECTTIVNGVRRSFYVYANGGKGFCKLHNWNCVNCDTFCAGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVTVKNGSIHLYFDKAGQKTYERHSLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCEESSAKSASVYYSQLMCQPILLLDQALVSDVGDSAEVAVKMFDAYVNTFSSTFNVPMEKLKTLVATAEAELAKNVSLDNVLSTFISAARQGFVDSDVETKDVVECLKLSHQSDIEVTGDSCNNYMLTYNKVENMTPRDLGACIDCSARHINAQVAKSHNIALIWNVKDFMSLSEQLRKQIRSAAKKNNLPFKLTCATTRQVVNVVTTKIALKGGKIVNNWLKQLIKVTLVFLFVAAIFYLITPVHVMSKHTDFSSEIIGYKAIDGGVTRDIASTDTCFANKHADFDTWFSQRGGSYTNDKACPLIAAVITREVGFVVPGLPGTILRTTNGDFLHFLPRVFSAVGNICYTPSKLIEYTDFATSACVLAAECTIFKDASGKPVPYCYDTNVLEGSVAYESLRPDTRYVLMDGSIIQFPNTYLEGSVRVVTTFDSEYCRHGTCERSEAGVCVSTSGRWVLNNDYYRSLPGVFCGVDAVNLLTNMFTPLIQPIGALDISASIVAGGIVAIVVTCLAYYFMRFRRAFGEYSHVVAFNTLLFLMSFTVLCLTPVYSFLPGVYSVIYLYLTFYLTNDVSFLAHIQWMVMFTPLVPFWITIAYIICISTKHFYWFFSNYLKRRVVFNGVSFSTFEEAALCTFLLNKEMYLKLRSDVLLPLTQYNRYLALYNKYKYFSGAMDTTSYREAACCHLAKALNDFSNSGSDVLYQPPQTSITSAVLQSGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCSGVTFQSAVKRTIKGTHHWLLLTILTSLLVLVQSTQWSLFFFLYENAFLPFAMGIIAMSAFAMMFVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVYDDGARRVWTLMNVLTLVYKVYYGNALDQAISMWALIISVTSNYSGVVTTVMFLARGIVFMCVEYCPIFFITGNTLQCIMLVYCFLGYFCTCYFGLFCLLNRYFRLTLGVYDYLVSTQEFRYMNSQGLLPPKNSIDAFKLNIKLLGVGGKPCIKVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRATLQAIASEFSSLPSYAAFATAQEAYEQAVANGDSEVVLKKLKKSLNVAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKVTSAMQTMLFTMLRKLDNDALNNIINNARDGCVPLNIIPLTTAAKLMVVIPDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEISMDNSPNLAWPLIVTALRANSAVKLQNNELSPVALRQMSCAAGTTQTACTDDNALAYYNTTKGGRFVLALLSDLQDLKWARFPKSDGTGTIYTELEPPCRFVTDTPKGPKVKYLYFIKGLNNLNRGMVLGSLAATVRLQAGNATEVPANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKMLCTHTGTGQAITVTPEANMDQESFGGASCCLYCRCHIDHPNPKGFCDLKGKYVQIPTTCANDPVGFTLKNTVCTVCGMWKGYGCSCDQLREPMLQSADAQSFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDDNLIDSYFVVKRHTFSNYQHEETIYNLLKDCPAVAKHDFFKFRIDGDMVPHISRQRLTKYTMADLVYALRHFDEGNCDTLKEILVTYNCCDDDYFNKKDWYDFVENPDILRVYANLGERVRQALLKTVQFCDAMRNAGIVGVLTLDNQDLNGNWYDFGDFIQTTPGSGVPVVDSYYSLLMPILTLTRALTAESHVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHFRELGVVHNQDVNLHSSRLSFKELLVYAADPAMHAASGNLLLDKRTTCFSVAALTNNVAFQTVKPGNFNKDFYDFAVSKGFFKEGSSVELKHFFFAQDGNAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDGGCINANQVIVNNLDKSAGFPFNKWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMNLKYAISAKNRARTVAGVSICSTMTNRQFHQKLLKSIAATRGATVVIGTSKFYGGWHNMLKTVYSDVENPHLMGWDYPKCDRAMPNMLRIMASLVLARKHTTCCSLSHRFYRLANECAQVLSEMVMCGGSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQHRLYECLYRNRDVDTDFVNEFYAYLRKHFSMMILSDDAVVCFNSTYASQGLVASIKNFKSVLYYQNNVFMSEAKCWTETDLTKGPHEFCSQHTMLVKQGDDYVYLPYPDPSRILGAGCFVDDIVKTDGTLMIERFVSLAIDAYPLTKHPNQEYADVFHLYLQYIRKLHDELTGHMLDMYSVMLTNDNTSRYWEPEFYEAMYTPHTVLQAVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLYKNTCVGSDNVTDFNAIATCDWTNAGDYILANTCTERLKLFAAETLKATEETFKLSYGIATVREVLSDRELHLSWEVGKPRPPLNRNYVFTGYRVTKNSKVQIGEYTFEKGDYGDAVVYRGTTTYKLNVGDYFVLTSHTVMPLSAPTLVPQEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPGTGKSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPIDKCSRIIPARARVECFDKFKVNSTLEQYVFCTVNALPETTADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLLTKGTLEPEYFNSVCRLMKTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINRPQIGVVREFLTRNPAWRKAVFISPYNSQNAVASKILGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKVGILCIMSDRDLYDKLQFTSLEIPRRNVATLQAENVTGLFKDCSKVITGLHPTQAPTHLSVDTKFKTEGLCVDIPGIPKDMTYRRLISMMGFKMNYQVNGYPNMFITREEAIRHVRAWIGFDVEGCHATREAVGTNLPLQLGFSTGVNLVAVPTGYVDTPNNTDFSRVSAKPPPGDQFKHLIPLMYKGLPWNVVRIKIVQMLSDTLKNLSDRVVFVLWAHGFELTSMKYFVKIGPERTCCLCDRRATCFSTASDTYACWHHSIGFDYVYNPFMIDVQQWGFTGNLQSNHDLYCQVHGNAHVASCDAIMTRCLAVHECFVKRVDWTIEYPIIGDELKINAACRKVQHMVVKAALLADKFPVLHDIGNPKAIKCVPQADVEWKFYDAQPCSDKAYKIEELFYSYATHSDKFTDGVCLFWNCNVDRYPANSIVCRFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFVNLKQLPFFYYSDSPCESHGKQVVSDIDYVPLKSATCITRCNLGGAVCRHHANEYRLYLDAYNMMISAGFSLWVYKQFDTYNLWNTFTRLQSLENVAFNVVNKGHFDGQQGEVPVSIINNTVYTKVDGVDVELFENKTTLPVNVAFELWAKRNIKPVPEVKILNNLGVDIAANTVIWDYKRDAPAHISTIGVCSMTDIAKKPTETICAPLTVFFDGRVDGQVDLFRNARNGVLITEGSVKGLQPSVGPKQASLNGVTLIGEAVKTQFNYYKKVDGVVQQLPETYFTQSRNLQEFKPRSQMEIDFLELAMDEFIERYKLEGYAFEHIVYGDFSHSQLGGLHLLIGLAKRFKESPFELEDFIPMDSTVKNYFITDAQTGSSKCVCSVIDLLLDDFVEIIKSQDLSVVSKVVKVTIDYTEISFMLWCKDGHVETFYPKLQSSQAWQPGVAMPNLYKMQRMLLEKCDLQNYGDSATLPKGIMMNVAKYTQLCQYLNTLTLAVPYNMRVIHFGAGSDKGVAPGTAVLRQWLPTGTLLVDSDLNDFVSDADSTLIGDCATVHTANKWDLIISDMYDPKTKNVTKENDSKEGFFTYICGFIQQKLALGGSVAIKITEHSWNADLYKLMGHFAWWTAFVTNVNASSSEAFLIGCNYLGKPREQIDGYVMHANYIFWRNTNPIQLSSYSLFDMSKFPLKLRGTAVMSLKEGQINDMILSLLSKGRLIIRENNRVVISSDVLVNN |
| Enzyme Length | 7096 |
| Uniprot Accession Number | P0DTD1 |
| Absorption | |
| Active Site | ACT_SITE 1674; /note="For PL1-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00444, ECO:0000269|PubMed:32726803"; ACT_SITE 1835; /note="For PL2-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"; ACT_SITE 3304; /note="For 3CL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00772, ECO:0000305|PubMed:32198291"; ACT_SITE 3408; /note="Nucleophile; for 3CL-PRO activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00772, ECO:0000269|PubMed:32198291"; ACT_SITE 5151; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 5152; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 5153; /evidence="ECO:0000255|PROSITE-ProRule:PRU01293"; ACT_SITE 6015; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6017; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6116; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6193; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6198; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; ACT_SITE 6686; /note="Proton donor; for uridylate-specific endoribonuclease nsp15 activity"; /evidence="ECO:0000269|PubMed:33504779, ECO:0000269|PubMed:33564093"; ACT_SITE 6701; /note="Proton acceptor; for uridylate-specific endoribonuclease nsp15 activity"; /evidence="ECO:0000269|PubMed:33504779, ECO:0000269|PubMed:33564093"; ACT_SITE 6741; /note="For uridylate-specific endoribonuclease nsp15 activity"; /evidence="ECO:0000269|PubMed:33504779"; ACT_SITE 6844; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 6928; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 6968; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300"; ACT_SITE 7001; /evidence="ECO:0000255|PROSITE-ProRule:PRU01300" |
| Activity Regulation | ACTIVITY REGULATION: [Papain-like protease nsp3]: Inhibited in vitro by GRL-0617. {ECO:0000269|PubMed:32726803}.; ACTIVITY REGULATION: [Proofreading exoribonuclease nsp14]: Inhibited by Remdesivir antiviral drug (GS-5734). {ECO:0000250|UniProtKB:P0C6X7}.; ACTIVITY REGULATION: [RNA-directed RNA polymerase nsp12]: Inhibited by Remdesivir antiviral drug (GS-5734) through non-obligate RNA chain termination. {ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208}.; ACTIVITY REGULATION: [3C-like proteinase nsp5]: Inhibited by pyridone-containing alpha-ketoamides compounds 13a and 13b. In turn, alpha-ketoamide 13b (tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate) inhibits SARS-CoV-2 replication in human lung cells (PubMed:32198291). Inhibited ex vivo by michael acceptor inhibitor N3 (PubMed:32272481). Inhibited ex vivo by compound 11a and 11b (PubMed:32321856). {ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481, ECO:0000269|PubMed:32321856}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [RNA-directed RNA polymerase nsp12]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}; CATALYTIC ACTIVITY: [Helicase nsp13]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000250|UniProtKB:P0C6X7}; CATALYTIC ACTIVITY: [Helicase nsp13]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:P0C6X7}; CATALYTIC ACTIVITY: [3C-like proteinase nsp5]: Reaction=TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.; EC=3.4.22.69; Evidence={ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481, ECO:0000269|PubMed:32321856}; CATALYTIC ACTIVITY: [Papain-like protease nsp3]: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:32726803}; CATALYTIC ACTIVITY: [2'-O-methyltransferase nsp16]: Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167, Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609; EC=2.1.1.57; Evidence={ECO:0000250|UniProtKB:P0C6X7}; CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp15]: Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284, ChEBI:CHEBI:173079, ChEBI:CHEBI:173080; Evidence={ECO:0000269|PubMed:33504779, ECO:0000269|PubMed:33564093}; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.-; 3.4.22.69; 2.7.7.48; 3.6.4.12; 3.6.4.13; 3.1.13.-; 4.6.1.-; 2.1.1.57 |
| Enzyme Function | FUNCTION: [Replicase polyprotein 1ab]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Host translation inhibitor nsp1]: Inhibits host translation by associating with the open head conformation of the 40S subunit (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). The C-terminus binds to and obstructs ribosomal mRNA entry tunnel (PubMed:33479166, PubMed:33080218, PubMed:32680882, PubMed:32908316). Thereby inhibits antiviral response triggered by innate immunity or interferons (PubMed:33080218, PubMed:32680882, PubMed:32979938). The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation (By similarity). Viral mRNAs less susceptible to nsp1-mediated inhibition of translation, because of their 5'-end leader sequence (PubMed:32908316, PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32680882, ECO:0000269|PubMed:32908316, ECO:0000269|PubMed:32979938, ECO:0000269|PubMed:33080218, ECO:0000269|PubMed:33479166}.; FUNCTION: [Non-structural protein 2]: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Papain-like protease nsp3]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication (By similarity). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:32733001). Prevents also host NF-kappa-B signaling (By similarity). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:32726803). Cleaves preferentially ISG15 from antiviral protein IFIH1 (MDA5), but not DDX58 (RIG-I) (PubMed:33727702). Can play a role in host ADP-ribosylation by binding ADP-ribose (PubMed:32578982). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32578982, ECO:0000269|PubMed:32726803, ECO:0000269|PubMed:32733001, ECO:0000269|PubMed:33727702}.; FUNCTION: [Non-structural protein 4]: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [3C-like proteinase nsp5]: Cleaves the C-terminus of replicase polyprotein at 11 sites (PubMed:32321856). Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291, PubMed:32272481). Also able to bind an ADP-ribose-1''-phosphate (ADRP) (By similarity) (PubMed:32198291, PubMed:32272481). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32198291, ECO:0000269|PubMed:32272481, ECO:0000269|PubMed:32321856}.; FUNCTION: [Non-structural protein 6]: Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic (By similarity). Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (By similarity). Binds to host TBK1 without affecting TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32979938}.; FUNCTION: [Non-structural protein 7]: Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208). Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers (By similarity). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208}.; FUNCTION: [Non-structural protein 8]: Plays a role in viral RNA synthesis (PubMed:32358203, PubMed:32277040, PubMed:32438371, PubMed:32526208). Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers (By similarity). Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218). Together with NSP9, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32277040, ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32438371, ECO:0000269|PubMed:32526208, ECO:0000269|PubMed:33080218}.; FUNCTION: [Non-structural protein 9]: May participate in viral replication by acting as a ssRNA-binding protein (By similarity). Interacts with ribosome signal recognition particle RNA (SRP) (PubMed:33080218). Together with NSP9, suppress protein integration into the cell membrane, thereby disrupting host immune defenses (PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:33080218}.; FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [RNA-directed RNA polymerase nsp12]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000305|PubMed:32277040, ECO:0000305|PubMed:32358203, ECO:0000305|PubMed:32438371, ECO:0000305|PubMed:32526208}.; FUNCTION: [Helicase nsp13]: Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium (By similarity). Binds to host TBK1 and inhibits TBK1 phosphorylation; the interaction with TBK1 decreases IRF3 phosphorylation, which leads to reduced IFN-beta production (PubMed:32979938). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:32979938}.; FUNCTION: [Proofreading exoribonuclease nsp14]: Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens. {ECO:0000250|UniProtKB:P0C6X7}.; FUNCTION: [Uridylate-specific endoribonuclease nsp15]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs (PubMed:33504779, PubMed:33564093). Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (PubMed:33504779, PubMed:33564093). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:33504779}.; FUNCTION: [2'-O-methyltransferase nsp16]: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (By similarity). N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system (By similarity). May disrupt host mRNA splicing in nucleus by interacting with pre-mRNA Recognition Domains ofthe U1 and U2 snRNAs (PubMed:33080218). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000269|PubMed:33080218}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 5606..5613; /note=NTP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00990 |
| Features | Active site (19); Beta strand (21); Chain (16); Compositional bias (2); Domain (28); Helix (20); Metal binding (40); Mutagenesis (15); Natural variant (45); Nucleotide binding (1); Region (7); Repeat (9); Site (16); Topological domain (13); Transmembrane (12); Turn (2); Zinc finger (1) |
| Keywords | 3D-structure;ATP-binding;Activation of host autophagy by virus;Decay of host mRNAs by virus;Endonuclease;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Exonuclease;Helicase;Host Golgi apparatus;Host cytoplasm;Host endoplasmic reticulum;Host endosome;Host gene expression shutoff by virus;Host mRNA suppression by virus;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host IRF3 by virus;Inhibition of host ISG15 by virus;Inhibition of host NF-kappa-B by virus;Inhibition of host RLR pathway by virus;Inhibition of host TBK1 by virus;Inhibition of host TLR pathway by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Leucine-rich repeat;Lyase;Membrane;Metal-binding;Methyltransferase;Modulation of host ubiquitin pathway by viral deubiquitinase;Modulation of host ubiquitin pathway by virus;Nuclease;Nucleotide-binding;Nucleotidyltransferase;Protease;RNA-binding;RNA-directed RNA polymerase;Reference proteome;Repeat;Ribosomal frameshifting;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral RNA replication;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | P0DTD1; P21281; Q8WVV9; P52306; Q9NUL3; P0DTC9; P0DTD1; Q8IYX8; Q9BZS1; P51114; P51116; Q9BYX4; P05161; Q64339; Q9H000; Q13064; O75360; Q9H5L6; J3QS39; P0CG48; O95429; P60880; Itself; Q92769; E9Q5R7; P59046; Q15750; P26842; Q16553; P0DTC7; P0DTD1; P0DTD1; P0DTD1; Itself; Q86Y26; P0DTD1; Itself; P51114; P51116; A8MTQ0; Q04864; P23497; P15884; P0DTD1; Itself; P0DTD1; P0DTD1; O15226; P0DTD1; O75360; Q9UHD2; Q92995; Q9BXI9; Q2TAC2; Q9BV73; P53675; Q9Y2V7; Q08379; A6NEM1; Q9Y6K9; O60229; P52954; Q9Y6D9; Q5JR59; A8MTQ0; O75360; Q04864; Q15427; Q96R06; Q13077; Q12933; P14373; Q86XT4; Itself; O75360; Q4VCS5; Q8WWH4; Q9H257; O95273; Q9Y2V7; Q04446; Q08379; A6NEM1; Q8IX15; Q9UKT9; O60229; P13646; Q7Z3Y8; Q15323; Q14532; Q6A163; P28838; P52954; Q6UWW0; Q5JR59; A8MTQ0; Q9HBI0; Q8ND90; Q86W92; O75360; P41219; P11217; Q8TBN0; Q96QF0; Q04864; Q9UHV2; Q96R06; Q9Y2D8; Q8N0S2; Q8WW24; Q9H5L6; Q9C040; P14373; O75382; Q13049; Q9BYV2; Q9UHP3; P08670; Q8N1B4; Q9UGI0 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Host translation inhibitor nsp1]: Host cytoplasm {ECO:0000269|PubMed:33060197}.; SUBCELLULAR LOCATION: [Non-structural protein 2]: Host cytoplasm {ECO:0000269|PubMed:33060197}. Host endosome {ECO:0000269|PubMed:33060197}.; SUBCELLULAR LOCATION: [Papain-like protease nsp3]: Host membrane {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6X7}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6X7}. Note=Localizes in virally-induced cytoplasmic double-membrane vesicles. {ECO:0000250|UniProtKB:P0C6X7}.; SUBCELLULAR LOCATION: [3C-like proteinase nsp5]: Host cytoplasm {ECO:0000269|PubMed:33060197}. Host Golgi apparatus {ECO:0000269|PubMed:33060197}.; SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P0C6X7}.; SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm {ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:33080218}. Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm {ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:33080218}. Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Host cytoplasm {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [Proofreading exoribonuclease nsp14]: Host cytoplasm {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum {ECO:0000269|PubMed:33060197}. Host endoplasmic reticulum.; SUBCELLULAR LOCATION: [Helicase nsp13]: Host endoplasmic reticulum-Golgi intermediate compartment {ECO:0000250|UniProtKB:P0C6X7}. Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp15]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}.; SUBCELLULAR LOCATION: [2'-O-methyltransferase nsp16]: Host nucleus. Host cytoplasm {ECO:0000269|PubMed:33080218}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed. {ECO:0000250|UniProtKB:P0C6X7}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (37); X-ray crystallography (790) |
| Cross Reference PDB | 5R7Y; 5R7Z; 5R80; 5R81; 5R82; 5R83; 5R84; 5R8T; 5RE4; 5RE5; 5RE6; 5RE7; 5RE8; 5RE9; 5REA; 5REB; 5REC; 5RED; 5REE; 5REF; 5REG; 5REH; 5REI; 5REJ; 5REK; 5REL; 5REM; 5REN; 5REO; 5REP; 5RER; 5RES; 5RET; 5REU; 5REV; 5REW; 5REX; 5REY; 5REZ; 5RF0; 5RF1; 5RF2; 5RF3; 5RF4; 5RF5; 5RF6; 5RF7; 5RF8; 5RF9; 5RFA; 5RFB; 5RFC; 5RFD; 5RFE; 5RFF; 5RFG; 5RFH; 5RFI; 5RFJ; 5RFK; 5RFL; 5RFM; 5RFN; 5RFO; 5RFP; 5RFQ; 5RFR; 5RFS; 5RFT; 5RFU; 5RFV; 5RFW; 5RFX; 5RFY; 5RFZ; 5RG0; 5RG1; 5RG2; 5RG3; 5RGG; 5RGH; 5RGI; 5RGJ; 5RGK; 5RGL; 5RGM; 5RGN; 5RGO; 5RGP; 5RGQ; 5RGR; 5RGS; 5RGT; 5RGU; 5RGV; 5RGW; 5RGX; 5RGY; 5RGZ; 5RH0; 5RH1; 5RH2; 5RH3; 5RH4; 5RH5; 5RH6; 5RH7; 5RH8; 5RH9; 5RHA; 5RHB; 5RHC; 5RHD; 5RHE; 5RHF; 5RL0; 5RL1; 5RL2; 5RL3; 5RL4; 5RL5; 5RL6; 5RL7; 5RL8; 5RL9; 5RLB; 5RLC; 5RLD; 5RLE; 5RLF; 5RLG; 5RLH; 5RLI; 5RLJ; 5RLK; 5RLL; 5RLM; 5RLN; 5RLO; 5RLP; 5RLQ; 5RLR; 5RLS; 5RLT; 5RLU; 5RLV; 5RLW; 5RLY; 5RLZ; 5RM0; 5RM1; 5RM2; 5RM3; 5RM4; 5RM5; 5RM6; 5RM7; 5RM8; 5RM9; 5RMA; 5RMB; 5RMC; 5RMD; 5RME; 5RMF; 5RMG; 5RMH; 5RMI; 5RMJ; 5RMK; 5RML; 5RMM; 5ROB; 5RS7; 5RS8; 5RS9; 5RSB; 5RSC; 5RSD; 5RSE; 5RSF; 5RSG; 5RSH; 5RSI; 5RSJ; 5RSK; 5RSL; 5RSM; 5RSN; 5RSO; 5RSP; 5RSQ; 5RSR; 5RSS; 5RST; 5RSU; 5RSV; 5RSW; 5RSX; 5RSY; 5RSZ; 5RT0; 5RT1; 5RT2; 5RT3; 5RT4; 5RT5; 5RT6; 5RT7; 5RT8; 5RT9; 5RTA; 5RTB; 5RTC; 5RTD; 5RTE; 5RTF; 5RTG; 5RTH; 5RTI; 5RTJ; 5RTK; 5RTL; 5RTM; 5RTN; 5RTO; 5RTP; 5RTQ; 5RTR; 5RTS; 5RTT; 5RTU; 5RTV; 5RTW; 5RTX; 5RTY; 5RTZ; 5RU0; 5RU1; 5RU2; 5RU3; 5RU4; 5RU5; 5RU6; 5RU7; 5RU8; 5RU9; 5RUA; 5RUC; 5RUD; 5RUE; 5RUF; 5RUG; 5RUH; 5RUI; 5RUJ; 5RUK; 5RUL; 5RUM; 5RUN; 5RUO; 5RUP; 5RUQ; 5RUR; 5RUS; 5RUT; 5RUU; 5RUV; 5RUW; 5RUX; 5RUY; 5RUZ; 5RV0; 5RV1; 5RV2; 5RV3; 5RV4; 5RV5; 5RV6; 5RV7; 5RV8; 5RV9; 5RVA; 5RVB; 5RVC; 5RVD; 5RVE; 5RVF; 5RVG; 5RVH; 5RVI; 5RVJ; 5RVK; 5RVL; 5RVM; 5RVN; 5RVO; 5RVP; 5RVQ; 5RVR; 5RVS; 5RVT; 5RVU; 5RVV; 5S18; 5S1A; 5S1C; 5S1E; 5S1G; 5S1I; 5S1K; 5S1M; 5S1O; 5S1Q; 5S1S; 5S1U; 5S1W; 5S1Y; 5S20; 5S22; 5S24; 5S26; 5S27; 5S28; 5S29; 5S2A; 5S2B; 5S2C; 5S2D; 5S2E; 5S2F; 5S2G; 5S2H; 5S2I; 5S2J; 5S2K; 5S2L; 5S2M; 5S2N; 5S2O; 5S2P; 5S2Q; 5S2R; 5S2S; 5S2T; 5S2U; 5S2V; 5S2W; 5S2X; 5S2Y; 5S2Z; 5S30; 5S31; 5S32; 5S33; 5S34; 5S35; 5S36; 5S37; 5S38; 5S39; 5S3A; 5S3B; 5S3C; 5S3D; 5S3E; 5S3F; 5S3G; 5S3H; 5S3I; 5S3J; 5S3K; 5S3L; 5S3M; 5S3N; 5S3O; 5S3P; 5S3Q; 5S3R; 5S3S; 5S3T; 5S3U; 5S3V; 5S3W; 5S3X; 5S3Y; 5S3Z; 5S40; 5S41; 5S42; 5S43; 5S44; 5S45; 5S46; 5S47; 5S48; 5S49; 5S4A; 5S4B; 5S4C; 5S4D; 5S4E; 5S4F; 5S4G; 5S4H; 5S4I; 5S4J; 5S4K; 5S6X; 5S6Y; 5S6Z; 5S70; 5S71; 5S72; 5S73; 5S74; 5SA4; 5SA5; 5SA6; 5SA7; 5SA8; 5SA9; 5SAA; 5SAB; 5SAC; 5SAD; 5SAE; 5SAF; 5SAG; 5SAH; 5SAI; 6LU7; 6LZE; 6M03; 6M0K; 6M2N; 6M2Q; 6M71; 6VWW; 6VXS; 6W01; 6W02; 6W4B; 6W4H; 6W61; 6W63; 6W6Y; 6W75; 6W9C; 6W9Q; 6WC1; 6WCF; 6WEN; 6WEY; 6WIQ; 6WJT; 6WKQ; 6WKS; 6WLC; 6WNP; 6WOJ; 6WQ3; 6WQD; 6WQF; 6WRH; 6WRZ; 6WTC; 6WTJ; 6WTK; 6WTM; 6WTT; 6WUU; 6WVN; 6WX4; 6WXC; 6WXD; 6WZU; 6X1B; 6X4I; 6XA4; 6XA9; 6XAA; 6XB0; 6XB1; 6XB2; 6XBG; 6XBH; 6XBI; 6XCH; 6XDH; 6XFN; 6XG3; 6XHM; 6XHU; 6XIP; 6XKF; 6XKH; 6XKM; 6XMK; 6XOA; 6XQS; 6XQT; 6XQU; 6XR3; 6Y2E; 6Y2F; 6Y2G; 6Y84; 6YB7; 6YNQ; 6YVA; 6YVF; 6YWK; 6YWL; 6YWM; 6YYT; 6YZ1; 6Z2E; 6Z5T; 6Z6I; 6Z72; 6ZCT; 6ZLW; 6ZM7; 6ZME; 6ZMI; 6ZMO; 6ZMT; 6ZN5; 6ZOJ; 6ZOK; 6ZON; 6ZP4; 6ZPE; 6ZRT; 6ZRU; 6ZSL; 7A1U; 7ABU; 7ADW; 7AEG; 7AF0; 7AGA; 7AHA; 7AK4; 7AKU; 7ALH; 7ALI; 7AMJ; 7ANS; 7AOL; 7AP6; 7APH; 7AQE; 7AQI; 7AQJ; 7AR5; 7AR6; 7ARF; 7AVD; 7AWR; 7AWS; 7AWU; 7AWW; 7AX6; 7AXM; 7AXO; 7AY7; 7B3E; 7B83; 7BAJ; 7BAK; 7BAL; 7BB2; 7BE7; 7BF3; 7BF4; 7BF5; 7BF6; 7BFB; 7BGP; 7BQ7; 7BQY; 7BRO; 7BRP; 7BTF; 7BUY; 7BV1; 7BV2; 7BZF; 7C2I; 7C2J; 7C2K; 7C2Q; 7C2Y; 7C6S; 7C6U; 7C7P; 7C8B; 7C8R; 7C8T; 7C8U; 7CA8; 7CAM; 7CB7; 7CBT; 7CJD; 7CJM; 7CMD; 7COM; 7CUT; 7CUU; 7CWB; 7CWC; 7CX9; 7D1M; 7D1O; 7D7K; 7D7L; 7DIY; 7E18; 7E19; 7EQ4; 7JFQ; 7JHE; 7JIB; 7JKV; 7JME; 7JOY; 7JP0; 7JP1; 7JPE; 7JPY; 7JPZ; 7JQ0; 7JQ1; 7JQ2; 7JQ3; 7JQ4; 7JQ5; 7JQB; 7JQC; 7JR3; 7JR4; 7JST; 7JSU; 7JT0; 7JT7; 7JU7; 7JUN; 7JVZ; 7JW8; 7JYC; 7JYY; 7JZ0; 7K0E; 7K0F; 7K0R; 7K1L; 7K1O; 7K3N; 7K3T; 7K40; 7K5I; 7K6D; 7K6E; 7K7P; 7K9P; 7KAG; 7KEG; 7KEH; 7KF4; 7KFI; 7KG3; 7KHP; 7KOA; 7KPH; 7KQO; 7KQP; 7KQW; 7KR0; 7KR1; 7KRI; 7KVL; 7KVR; 7KX5; 7KXB; 7KYU; 7L0D; 7L10; 7L11; 7L12; 7L13; 7L14; 7L1F; 7L5D; 7L6R; 7L6T; 7L8I; 7L8J; 7LB7; 7LBN; 7LBR; 7LBS; 7LCO; 7LCS; 7LCT; 7LDL; 7LDX; 7LFE; 7LFP; 7LFZ; 7LG2; 7LG3; 7LG7; 7LGO; 7LKD; 7LKE; 7LKR; 7LKS; 7LKT; 7LKU; 7LKV; 7LKW; 7LKX; 7LLF; 7LLZ; 7LMD; 7LME; 7LMF; 7LOS; 7LTJ; 7LW3; 7LW4; 7LYH; 7LYI; 7LZT; 7LZU; 7LZV; 7LZW; 7LZX; 7LZY; 7LZZ; 7M00; 7M01; 7M02; 7M03; 7M04; 7M2P; 7M8M; 7M8N; 7M8O; 7M8P; 7M8X; 7M8Y; 7M8Z; 7M90; 7M91; 7MBG; 7MBI; 7MC5; 7MC6; 7ME0; 7MGR; 7MGS; 7MHF; 7MHG; 7MHH; 7MHI; 7MHJ; 7MHK; 7MHL; 7MHM; 7MHN; 7MHO; 7MHP; 7MHQ; 7MNG; 7MPB; 7MRR; 7MSW; 7MSX; 7N06; 7N0B; 7N0C; 7N0D; 7N33; 7N3K; 7N44; 7N5Z; 7N6N; 7N7R; 7N7U; 7N7W; 7N7Y; 7N83; 7N89; 7N8C; 7NBR; 7NBS; 7NBY; 7NEV; 7NF5; 7NFV; 7NG3; 7NG6; 7NIO; 7NN0; 7NNG; 7NTS; 7O7Y; 7O7Z; 7O80; 7O81; 7ORR; 7ORU; 7ORV; 7ORW; 7R7H; 7RB0; 7RB2; 7RBZ; 7RC0; 7RN0; 7RN1; 7RQG; 7S3K; 7S3S; 7S4B; 7SI9; |
| Mapped Pubmed ID | 19465771; 20124702; 22505256; 32304108; 32382072; 32511376; 32511378; 32511411; 32541865; 32581217; 32592996; 32709886; 32709887; 32728018; 32737471; 32747425; 32845033; 32855413; 32880863; 32887884; 32895623; 32905393; 32908976; 32939273; 32981460; 32994211; 32995777; 33028810; 33036230; 33054210; 33060199; 33063790; 33067239; 33152262; 33158912; 33158944; 33163253; 33188728; 33202171; 33208735; 33234675; 33283984; 33319167; 33473130; 33503819; 33510133; 33531496; 33542181; 33594371; 33602867; 33631104; 33636189; 33691601; 33755450; 33786375; 33795671; 33811162; 33821277; 33850605; 33853786; 33864621; 33891389; 33956156; 33972410; 33972941; 34029205; 34031399; 34041486; 34045440; 34075025; 34078893; 34118724; 34131072; 34132580; 34161756; 34168183; 34174328; 34197805; 34210738; 34213885; 34242027; 34285133; 34288674; 34313428; 34315827; 34331944; 34347470; 34381037; 34403466; 34403647; 34408808; 34414360; 34437808; 34506130; 34528437; 34570415; 34705466; 34756886; 34769210; 34778773; 34793155; 34804549; 34865476; |
| Motif | |
| Gene Encoded By | |
| Mass | 794,058 |
| Kinetics | |
| Metal Binding | METAL 4327; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4330; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4336; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4343; /note="Zinc 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4370; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4373; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4381; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4383; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01297"; METAL 4687; /note="Zinc 3; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 4693; /note="Zinc 3; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 4698; /note="Zinc 3; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 4702; /note="Zinc 3; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 4879; /note="Zinc 4; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 5034; /note="Zinc 4; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 5037; /note="Zinc 4; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 5038; /note="Zinc 4; structural"; /evidence="ECO:0000269|PubMed:32358203, ECO:0000269|PubMed:32526208"; METAL 5329; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5332; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5340; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5343; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5350; /note="Zinc 5"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5353; /note="Zinc 6; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5357; /note="Zinc 6; via pros nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5363; /note="Zinc 6"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5374; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5379; /note="Zinc 7; via pros nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5396; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 5399; /note="Zinc 7"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"; METAL 6132; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6135; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6151; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6154; /note="Zinc 8"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6182; /note="Zinc 9"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6186; /note="Zinc 9"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6189; /note="Zinc 9"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6204; /note="Zinc 9"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01298"; METAL 6377; /note="Zinc 10"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6398; /note="Zinc 10"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6409; /note="Zinc 10"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299"; METAL 6412; /note="Zinc 10"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01299" |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67020; RHEA:67732 |
| Cross Reference Brenda | 2.7.7.48; |