♦Replicase polyprotein 1ab (pp1ab) (ORF1ab polyprotein) [Cleaved into: Host translation inhibitor nsp1 (nsp1) (p28)
♦ Non-structural protein 2 (nsp2) (p65)
♦ Papain-like proteinase (PL-PRO) (EC 3.4.19.12) (EC 3.4.22.69) (Non-structural protein 3) (nsp3) (p210)
♦ Non-structural protein 4 (nsp4) (Peptide HD2) (p44)
♦ 3C-like proteinase (3CL-PRO) (3CLp) (EC 3.4.22.-) (M-PRO) (nsp5) (p27)
♦ Non-structural protein 6 (nsp6)
♦ Non-structural protein 7 (nsp7) (p10)
♦ Non-structural protein 8 (nsp8) (p22)
♦ Non-structural protein 9 (nsp9) (p12)
♦ Non-structural protein 10 (nsp10) (Growth factor-like peptide) (GFL) (p15)
♦ RNA-directed RNA polymerase (Pol) (RdRp) (EC 2.7.7.48) (nsp12) (p100)
♦ Helicase (Hel) (EC 3.6.4.12) (EC 3.6.4.13) (nsp13) (p67)
♦ Guanine-N7 methyltransferase (ExoN) (EC 2.1.1.-) (EC 3.1.13.-) (nsp14)
♦ Uridylate-specific endoribonuclease (EC 3.1.-.-) (NendoU) (nsp15) (p35)
♦ 2'-O-methyltransferase (EC 2.1.1.-) (nsp16)]

NC_006577.2 ;  AY597011.2 

MIKTSKYGLGFKWAPEFRWLLPDAAEELASPMKSDEGGLCPSTGQAMESVGFVYDNHVKIDCRCILGQEWHVQSNLIRDIFVHEDLHVVEVLTKTAVKSG
TAILIKSPLHSLGGFPKGYVMGLFRSYKTKRYVVHHLSMTTSTTNFGEDFLGWIVPFGFMPSYVHKWFQFCRLYIEESDLIISNFKFDDYDFSVEDAYAE
VHAEPKGKYSQKAYALLRQYRGIKPVLFVDQYGCDYSGKLADCLQAYGHYSLQDMRQKQSVWLANCDFDIVVAWHVVRDSRFVMRLQTIATICGIKYVAQ
PTEDVVDGDVVIREPVHLLSADAIVLKLPSLMKVMTHMDDFSIKSIYNVDLCDCGFVMQYGYVDCFNDNCDFYGWVSGNMMDGFSCPLCCTVYDSSEVKA
QSSGVIPENPVLFTNSTDTVNHDSFNLYGYSVTPFGSCIYWSPRPGLWIPIIKSSVKSYDDLVYSGVVGCKSIVKETALITHALYLDYVQCKCGNLEQNH
ILGVNNSWCRQLLLNRGDYNMLLKNIDLFVKRRADFACKFAVCGDGFVPFLLDGLIPRSYYLIQSGIFFTSLMSQFSQEVSDMCLKMCILFMDRVSVATF
YIEHYVNRLVTQFKLLGTTLVNKMVNWFNTMLDASAPATGWLLYQLLNGLFVVSQANFNFVALIPDYAKILVNKFYTFFKLLLECVTVDVLKDMPVLKTI
NGLVCIVGNKFYNVSTGLIPGFVLPCNAQEQQIYFFEGVAESVIVEDDVIENVKSSLSSYEYCQPPKSVEKICIIDNMYMGKCGDKFFPIVMNDKNICLL
DQAWRFPCAGRKVNFNEKPVVMEIPSLMTVKVMFDLDSTFDDILGKVCSEFEVEKGVTVDDFVAVVCDAIENALNSCKEHPVVGYQVRAFLNKLNENVVY
LFDEAGDEAMASRMYCTFAIEDVEDVISSEAVEDTIDGVVEDTINDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDV
VTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNDDEDVVTGDNNDEEIVTGDNDDQIV
VTGDDVDDIESIYDFDTYKALLVFNDVYNDALFVSYGSSVETETYFKVNGLWSPTITHTNCWLRSVLLVMQKLPFKFKDLAIENMWLSYKVGYNQSFVDY
LLTTIPKAIVLPQGGFVADFAYWFLNQFDINAYANWCCLKCGFSFDLNGLDALFFYGDIVSHVCKCGHNMTLIAADLPCTLHFSLFDDNFCAFCTPKKIF
IAACAVDVNVCHSVAVIGDEQIDGKFVTKFSGDKFDFIVGYGMSFSMSSFELPQLYGLCITPNVCFVKGDIINVARLVKADVIVNPANGHMLHGGGVAKA
IAVAAGKKFSKETAAMVKSKGVCQVGDCYVSTGGKLCKTILNIVGPDARQDGRQSYVLLARAYKHLNNYDCCLSTLISAGIFSVPADVSLTYLLGVVDKQ
VILVSNNKEDFDIIQKCQITSVVGTKALAVRLTANVGRVIKFETDAYKLFLSGDDCFVSNSSVIQEVLLLRHDIQLNNDVRDYLLSKMTSLPKDWRLINK
FDVINGVKTVKYFECPNSIYICSQGKDFGYVCDGSFYKATVNQVCVLLAKKIDVLLTVDGVNFKSISLTVGEVFGKILGNVFCDGIDVTKLKCSDFYADK
ILYQYENLSLADISAVQSSFGFDQQQLLAYYNFLTVCKWSVVVNGPFFSFEQSHNNCYVNVACLMLQHINLKFNKWQWQEAWYEFRAGRPHRLVALVLAK
GHFKFDEPSDATDFIRVVLKQADLSGAICELELICDCGIKQESRVGVDAVMHFGTLAKTDLFNGYKIGCNCAGRIVHCTKLNVPFLICSNTPLSKDLPDD
VVAANMFMGVGVGHYTHLKCGSPYQHYDACSVKKYTGVSGCLTDCLYLKNLTQTFTSMLTNYFLDDVEMVAYNPDLSQYYCDNGKYYTKPIIKAQFKPFA
KVDGVYTNFKLVGHDICAQLNDKLGFNVDLPFVEYKVTVWPVATGDVVLASDDLYVKRYFKGCETFGKPVIWFCHDEASLNSLTYFNKPSFKSENRYSVL
SVDSVSEESQGNVVTSVMESQISTKEVKLKGVRKTVKIEDAIIVNDENSSIKVVKSLSLVDVWDMYLTGCDYVVWVANELSRLVKSPTVREYIRYGIKPI
TIPIDLLCLRDDNQTLLVPKIFKARAIEFYGFLKWLFIYVFSLLHFTNDKTIFYTTEIASKFTFNLFCLALKNAFQTFRWSIFIKGFLVVATVFLFWFNF
LYINVIFSDFYLPNISVFPIFVGRIVMWIKATFGLVTICDFYSKLGVGFTSHFCNGSFICELCHSGFDMLDTYAAIDFVQYEVDRRVLFDYVSLVKLIVE
LVIGYSLYTVWFYPLFCLIGLQLFTTWLPDLFMLETMHWLIRFIVFVANMLPAFVLLRFYIVVTAMYKVVGFIRHIVYGCNKAGCLFCYKRNCSVRVKCS
TIVGGVIRYYDITANGGTGFCVKHQWNCFNCHSFKPGNTFITVEAAIELSKELKRPVNPTDASHYVVTDIKQVGCMMRLFYDRDGQRVYDDVDASLFVDI
NNLLHSKVKVVPNLYVVVVESDADRANFLNAVVFYAQSLYRPILLVDKKLITTACNGISVTQTMFDVYVDTFMSHFDVDRKSFNNFVNIAHASLREGVQL
EKVLDTFVGCVRKCCSIDSDVETRFITKSMISAVAAGLEFTDENYNNLVPTYLKSDNIVAADLGVLIQNGAKHVQGNVAKAANISCIWFIDAFNQLTADL
QHKLKKACVKTGLKLKLTFNKQEASVPILTTPFSLKGGVVLSNLLYILFFVSLICFILLWALLPTYSVYKSDIHLPAYASFKVIDNGVVRDISVNDLCFA
NKFFQFDQWYESTFGSVYYHNSMDCPIVVAVMDEDIGSTMFNVPTKVLRHGFHVLHFLTYAFASDSVQCYTPHIQISYNDFYASGCVLSSLCTMFKRGDG
TPHPYCYSDGVMKNASLYTSLVPHTRYSLANSNGFIRFPDVISEGIVRIVRTRSMTYCRVGACEYAEEGICFNFNSSWVLNNDYYRSMPGTFCGRDLFDL
FYQFFSSLIRPIDFFSLTASSIFGAILAIVVVLVFYYLIKLKRAFGDYTSVVVINVVVWCINFLMLFVFQVYPICACVYACFYFYVTLYFPSEISVIMHL
QWIVMYGAIMPFWFCVTYVAMVIANHVLWLFSYCRKIGVNVCSDSTFEETSLTTFMITKDSYCRLKNSVSDVAYNRYLSLYNKYRYYSGKMDTAAYREAA
CSQLAKAMETFNHNNGNDVLYQPPTASVSTSFLQSGIVKMVSPTSKIEPCIVSVTYGSMTLNGLWLDDKVYCPRHVICSSSNMNEPDYSALLCRVTLGDF
TIMSGRMSLTVVSYQMQGCQLVLTVSLQNPYTPKYTFGNVKPGETFTVLAAYNGRPQGAFHVTMRSSYTIKGSFLCGSCGSVGYVLTGDSVKFVYMHQLE
LSTGCHTGTDFTGNFYGPYRDAQVVQLPVKDYVQTVNVIAWLYAAILNNCAWFVQNDVCSTEDFNVWAMANGFSQVKADLVLDALASMTGVSIETLLAAI
KRLYMGFQGRQILGSCTFEDELAPSDVYQQLAGVKLQSKTKRFIKETIYWILISTFLFSCIISAFVKWTIFMYINTHMIGVTLCVLCFVSFMMLLVKHKH
FYLTMYIIPVLCTLFYVNYLVVYKEGFRGFTYVWLSYFVPAVNFTYVYEVFYGCILCVFAIFITMHSINHDIFSLMFLVGRIVTLISMWYFGSNLEEDVL
LFITAFLGTYTWTTILSLAIAKIVANWLSVNIFYFTDVPYIKLILLSYLFIGYILSCYWGFFSLLNSVFRMPMGVYNYKISVQELRYMNANGLRPPRNSF
EAILLNLKLLGIGGVPVIEVSQIQSKLTDVKCANVVLLNCLQHLHVASNSKLWQYCSVLHNEILSTSDLSVAFDKLAQLLIVLFANPAAVDTKCLASIDE
VSDDYVQDSTVLQALQSEFVNMASFVEYEVAKKNLADAKNSGSVNQQQIKQLEKACNIAKSVYERDKAVARKLERMADLALTNMYKEARINDKKSKVVSA
LQTMLFSMVRKLDNQALNSILDNAVKGCVPLSAIPALAANTLTIVIPDKQVFDKVVDNVYVTYAGSVWHIQTVQDADGINKQLTDISVDSNWPLVIIANR
YNEVANAVMQNNELMPHKLKIQVVNSGSDMNCNIPTQCYYNNGSSGRIVYAVLSDVDGLKYTKIMKDDGNCVVLELDPPCKFSIQDVKGLKIKYLYFIKG
CNTLARGWVVGTLSSTIRLQAGVATEYAANSSILSLCAFSVDPKKTYLDYIQQGGVPIINCVKMLCDHAGTGMAITIKPEATINQDSYGGASVCIYCRAR
VEHPDVDGICKLRGKFVQVPLGIKDPILYVLTHDVCQVCGFWRDGSCSCVGSSVAVQSKDLNFLNRVRGTSVNARLVPCASGLSTDVQLRAFDICNTNRA
GIGLYYKVNCCRFQRIDDDGNKLDKFFVVKRTNLEVYNKEKTYYELTKSCGVVAEHDFFTFDIDGSRVPHIVRRNLSKYTMLDLCYALRHFDRNDCSILC
EILCEYADCKESYFSKKDWYDFVENPDIINIYKKLGPIFNRALLNTVIFADTLVEVGLVGVLTLDNQDLYGQWYDFGDFIQTAPGFGVAVADSYYSYMMP
MLTMCHVLDCELFVNDSYRQFDLVQYDFTDYKLELFNKYFKYWGMKYHPNTVDCDNDRCIIHCANFNILFSMVLPNTCFGPLVRQIFVDGVPFVVSIGYH
YKELGVVMNLDVDTHRYRLSLKDLLLYAADPAMHVASASALLDLRTCCFSVAAITSGIKFQTVKPGNFNQDFYEFVKSKGLFKEGSTVDLKHFFFTQDGN
AAITDYNYYKYNLPTMVDIKQLLFVLEVVYKYFEIYDGGCIPASQVIVNNYDKSAGYPFNKFGKARLYYEALSFEEQNEIYAYTKRNVLPTLTQMNLKYA
ISAKNRARTVAGVSILSTMTGRMFHQKCLKSIAATRGVPVVIGTTKFYGGWDDMLRHLIKDVDNPVLMGWDYPKCDRAMPNILRIVSSLVLARKHEFCCS
HGDRFYRLANECAQVLSEIVMCGGCYYVKPGGTSSGDATTAFANSVFNICQAVTANVCSLMACNGHKIEDLSIRNLQKRLYSNVYRTDYVDYTFVNEYYE
FLCKHFSMMILSDDGVVCYNSDYASKGYIANISVFQQVLYYQNNVFMSESKCWVENDITNGPHEFCSQHTMLVKIDGDYVYLPYPDPSRILGAGCFVDDL
LKTDSVLLIERFVSLAIDAYPLVHHENEEYQKVFRVYLEYIKKLYNDLGTQILDSYSVILSTCDGLKFTEESFYKNMYLKSAVMQSVGACVVCSSQTSLR
CGSCIRKPLLCCKCCYDHVMATNHKYVLSVSPYVCNAPNCDVSDVTKLYLGGMSYYCENHKPHYSFKLVMNGMVFGLYKQSCTGSPYIDDFNKIASCKWT
EVDDYVLANECIERLKLFAAETQKATEEAFKQSYASATIQEIVSDREVILCWETGKVKPPLNKNYVFTGYHFTSTGKTVLGEYVFDKSELTNGVYYRATT
TYKLSIGDVFVLTSHSVASLSAPTLVPQENYASIRFSSVYSVPLVFQNNVANYQHIGMKRYCTVQGPPGTGKSHLAIGLAVYYYTARVVYTAASHAAVDA
LCEKAYKFLNINDCTRIIPAKVRVDCYDKFKINDTTCKYVFTTINALPELVTDIVVVDEVSMLTNYELSVINARIKAKHYVYIGDPAQLPAPRVLLSKGS
LEPRHFNSITKIMCCLGPDIFLGNCYRCPKEIVETVSALVYDNKLKAKNDNSSLCFKVYFKGQTTHESSSAVNIQQIYLISKFLKANPVWNSAVFISPYN
SQNYVAKRVLGVQTQTVDSAQGSEYDYVIYSQTAETAHSVNVNRFNVAITRAKKGIFCVMSNMQLFESLNFITLPLDKIQNQTLPRLHCTTNLFKDCSKS
CLGYHPAHAPSFLAVDDKYKVNENLAVNLNICEPVLTYSRLISLMGFKLDLTLDGYSKLFITKDEAIKRVRGWVGFDVEGAHATRENIGTNFPLQIGFST
GVDFVVEATGLFAERDCYTFKKTVAKAPPGEKFKHLIPLMSKGQKWDIVRIRIVQMLSDYLLDLSDSVVFITWSASFELTCLRYFAKLGRELNCNVCSNR
ATCYNSRTGYYGCWRHSYTCDYVYNPLIVDIQQWGYTGSLTSNHDIICNVHKGAHVASADAIMTRCLAIYDCFCKSVNWNLEYPIISNEVSINTSCRLLQ
RVMLKAAMLCNRYNLCYDIGNPKGLACVKDYEFKFYDAFPVAKSVKQLFYVYDVHKDNFKDGLCMFWNCNVDKYPSNSIVCRFDTRVLNKLNLPGCNGGS
LYVNKHAFHTNPFTRTVFENLKPMPFFYYSDTPCVYVDGLESKQVDYVPLRSATCITRCNLGGAVCSKHAEEYCNYLESYNIVTTAGFTFWVYKNFDFYN
LWNTFTTLQSLENVIYNLVNVGHYDGRTGELPCAIMNDKVVVKINNVDTVIFKNNTSFPTNIAVELFTKRSIRHHPELKILRNLNIDICWKHVLWDYVKD
SLFCSSTYGVCKYTDLKFIENLNILFDGRDTGALEAFRKARNGVFISTEKLSRLSMIKGPQRADLNGVIVDKVGELKVEFWFAMRKDGDDVIFSRTDSLC
SSHYWSPQGNLGGNCAGNVIGNDALTRFTIFTQSRVLSSFEPRSDLERDFIDMDDNLFIAKYGLEDYAFDHIVYGSFNHKVIGGLHLLIGLFRRKKKSNL
LIQEFLQYDSSIHSYFITDQECGSSKSVCTVIDLLLDDFVSIVKSLNLSCVSKVVNINVDFKDFQFMLWCNDNKIMTFYPKMQATNDWKPGYSMPVLYKY
LNVPLERVSLWNYGKPINLPTGCMMNVAKYTQLCQYLNTTTLAVPVNMRVLHLGAGSDKEVAPGSAVLRQWLPSGSILVDNDLNPFVSDSLVTYFGDCMT
LPFDCHWDLIISDMYDPLTKNIGDYNVSKDGFFTYICHLIRDKLSLGGSVAIKITEFSWNADLYKLMSCFAFWTVFCTNVNASSSEGFLIGINYLGKSSF
EIDGNVMHANYLFWRNSTTWNGGAYSLFDMTKFSLKLAGTAVVNLRPDQLNDLVYSLIERGKLLVRDTRKEIFVGDSLVNTC

♦The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
♦ Host translation inhibitor nsp1: Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.
♦ 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.
♦ Papain-like proteinase: Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.
♦ Non-structural protein 4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.
♦ Proteinase 3CL-PRO: Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).
♦ Non-structural protein 6: Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.
♦ Non-structural protein 7: 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.
♦ Non-structural protein 8: 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.
♦ Non-structural protein 9: May participate in viral replication by acting as a ssRNA-binding protein.
♦ 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.
♦ RNA-directed RNA polymerase: Responsible for replication and transcription of the viral RNA genome.
♦ Helicase: 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.
♦ Guanine-N7 methyltransferase: 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.
♦ Uridylate-specific endoribonuclease: Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.
♦ 2'-O-methyltransferase: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. 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.

♦ Papain-like proteinase: Host membrane
♦ Multi-pass membrane protein. Host cytoplasm C6X7.
♦ Non-structural protein 4: Host membrane
♦ Multi-pass membrane protein. Host cytoplasm. Note=Localizes in virally-induced cytoplasmic double-membrane vesicles. C6X7.
♦ Non-structural protein 6: Host membrane
♦ Multi-pass membrane protein .
♦ Non-structural protein 7: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.
♦ Non-structural protein 8: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.
♦ Non-structural protein 9: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.
♦ Non-structural protein 10: Host cytoplasm, host perinuclear region . Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.
♦ Helicase: Host endoplasmic reticulum-Golgi intermediate compartment . Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA.
♦ Uridylate-specific endoribonuclease: Host cytoplasm, host perinuclear region .

♦DOMAIN 1123 1373 Peptidase C16 1.
♦ DOMAIN 1351 1522 Macro.
♦ DOMAIN 1718 1978 Peptidase C16 2.
♦ DOMAIN 3335 3637 Peptidase C30.
♦ DOMAIN 5065 5227 RdRp catalytic.
♦ DOMAIN 5386 5469 CV ZBD.
♦ DOMAIN 5641 5822 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 5823 5992 (+)RNA virus helicase C-terminal.

♦ACT_SITE 1161 1161 For PL1-PRO activity.
♦ ACT_SITE 1312 1312 For PL1-PRO activity.
♦ ACT_SITE 1757 1757 For PL2-PRO activity.
♦ ACT_SITE 1914 1914 For PL2-PRO activity.
♦ ACT_SITE 3375 3375 For 3CL-PRO activity.
♦ ACT_SITE 3479 3479 For 3CL-PRO activity.