ID P0C6Y4; PN Putative 2'-O-methyl transferase; GN rep; OS 229032; SL Nucleus Position: SL-0382; SL Comments: [Non-structural protein 1]: Host cytoplasm {ECO:0000269|PubMed:26773386}. Host nucleus {ECO:0000269|PubMed:26773386}. [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Non-structural protein 4]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Non-structural protein 6]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}. [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}. [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}. [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}. [Helicase]: Host endoplasmic reticulum-Golgi intermediate compartment {ECO:0000305}. Note=The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. {ECO:0000250}. [Uridylate-specific endoribonuclease]: Host cytoplasm, host perinuclear region {ECO:0000250}. DR UNIPROT: P0C6Y4; DR UNIPROT: Q91AV2; DR PDB: 5HIY; DR PDB: 5HIZ; DR Pfam: PF13087; DR Pfam: PF06471; DR Pfam: PF06460; DR Pfam: PF09401; DR Pfam: PF19215; DR Pfam: PF19216; DR Pfam: PF19219; DR Pfam: PF19212; DR Pfam: PF19211; DR Pfam: PF19218; DR Pfam: PF16348; DR Pfam: PF19217; DR Pfam: PF19213; DR Pfam: PF08716; DR Pfam: PF08717; DR Pfam: PF08710; DR Pfam: PF08715; DR Pfam: PF06478; DR Pfam: PF01661; DR Pfam: PF05409; DR Pfam: PF00680; DR PROSITE: PS51961; DR PROSITE: PS51952; DR PROSITE: PS51954; DR PROSITE: PS51962; DR PROSITE: PS52000; DR PROSITE: PS51948; DR PROSITE: PS51960; DR PROSITE: PS51991; DR PROSITE: PS51990; DR PROSITE: PS51989; DR PROSITE: PS51992; DR PROSITE: PS51943; DR PROSITE: PS51944; DR PROSITE: PS51946; DR PROSITE: PS51949; DR PROSITE: PS51950; DR PROSITE: PS51951; DR PROSITE: PS51653; DR PROSITE: PS51442; DR PROSITE: PS51154; DR PROSITE: PS51958; DR PROSITE: PS51947; DR PROSITE: PS51955; DR PROSITE: PS51953; DR PROSITE: PS51124; DR PROSITE: PS51657; DE Function: The non-structural protein 1 (nsp1) protein plays a role in the inhibition of host interferon and pro-inflammatory cytokines production. Suppresses host RELA/p65 activation by blocking NFKBIA phosphorylation (PubMed:28715653). Targets also the RLR pathway downstream of the IRF3 activation by targeting host CREBBP to proteasomal degradation (PubMed:26773386). {ECO:0000269|PubMed:26773386, ECO:0000269|PubMed:28715653}. 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. The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N- terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 (By similarity). {ECO:0000250}. [3C-like proteinase]: Responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|- [SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln- CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}. The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) (By similarity). {ECO:0000250}. The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction. {ECO:0000250}. Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter. {ECO:0000250}. Nsp9 is a ssRNA-binding protein. {ECO:0000250}. [Uridylate-specific endoribonuclease]: 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. 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) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7}. DE Reference Proteome: No; DE Interaction: P0C6X1; IntAct: EBI-26366740; Score: 0.44 DE Interaction: P0C6Y4; IntAct: EBI-25590339; Score: 0.56 GO GO:0030430; GO GO:0044172; GO GO:0033644; GO GO:0042025; GO GO:0044220; GO GO:0016021; GO GO:0000175; GO GO:0005524; GO GO:0016887; GO GO:0004843; GO GO:0004197; GO GO:0003678; GO GO:0004519; GO GO:0042802; GO GO:0016829; GO GO:0004482; GO GO:0004483; GO GO:0008242; GO GO:0003723; GO GO:0003724; GO GO:0003968; GO GO:0008270; GO GO:0006351; GO GO:0039520; GO GO:0039648; GO GO:0006508; GO GO:0039644; GO GO:0039548; GO GO:0019079; GO GO:0019082; TP Membrane Topology: Transmembrane; Source: UniProt - Sequence Analysis {ECO:0000255}; SQ MASNHVTLAFANDAEISAFGFCTASEAVSYYSEAAASGFMQCRFVSLDLADTVEGLLPEDYVMVVIGTTKLSAYVDTFGS SQ RPRNICGWLLFSNCNYFLEELELTFGRRGGNIVPVDQYMCGADGKPVLQESEWEYTDFFADSEDGQLNIAGITYVKAWIV SQ ERSDVSYASQNLTSIKSITYCSTYEHTFLDGTAMKVARTPKIKKNVVLSEPLATIYREIGSPFVDNGSDARSIIRRPVFL SQ HAFVKCKCGSYHWTVGDWTSYVSTCCGFKCKPVLVASCSAMPGSVVVTRAGAGTGVKYYNNMFLRHVADIDGLAFWRILK SQ VQSKDDLACSGKFLEHHEEGFTDPCYFLNDSSLATKLKFDILSGKFSDEVKQAIIAGHVVVGSALVDIVDDALGQPWFIR SQ KLGDLASAPWEQLKAVVRGLGLLSDEVVLFGKRLSCATLSIVNGVFEFLADVPEKLAAAVTVFVNFLNEFFESACDCLKV SQ GGKTFNKVGSYVLFDNALVKLVKAKARGPRQAGICEVRYTSLVVGSTTKVVSKRVENANVNLVVVDEDVTLNTTGRTVVV SQ DGLAFFESDGFYRHLADADVVIEHPVYKSACELKPVFECDPIPDFPLPVAASVAELCVQTDLLLKNYNTPYKTYSCVVRG SQ DKCCITCTLQFKAPSYVEDAVNFVDLCTKNIGTAGFHEFYITAHEQQDLQGFLTTCCTMSGFECFMPTIPQCPAVLEEID SQ GGSIWRSFITGLNTMWDFCKRLKVSFGLDGIVVTVARKFKRLGALLAEMYNTYLSTVVENLVLAGVSFKYYATSVPKIVL SQ GGCFHSVKSVFASVFQIPVQAGIEKFKVFLNCVHPVVPRVIETSFVELEETTFKPPALNGGIAIVDGFAFYYDGTLYYPT SQ DGNSVVPICFKKKGGGDVKFSDEVSVKTIDPVYKVSLEFEFESETIMAVLNKAVGNRIKVTGGWDDVVEYINVAIEVLKD SQ HVEVPKYYIYDEEGGTDPNLPVMVSQWPLNDDTISQDLLDVEVVTDAPIDSEGDEVDSSAPEKVADVANSEPGDDGLPVA SQ PETNVESEVEEVAATLSFIKDTPSTVTKDPFAFDFVSYGGLKVLRQSHNNCWVTSTLVQLQLLGIVDDPAMELFSAGRVG SQ PMVRKCYESQKAILGSLGDVSACLESLTKDLHTLKITCSVVCGCGTGERIYEGCAFRMTPTLEPFPYGACAQCAQVLMHT SQ FKSIVGTGIFCRDTTALSLDSLVVKPLCAAAFIGKDSGHYVTNFYDAAMAIDGYGRHQIKYDTLNTICVKDVNWTAPLVP SQ AVDSVVEPVVKPFYSYKNVDFYQGDFSDLVKLPCDFVVNAANEKLSHGGGIAKAIDVYTKGMLQKCSNDYIKAHGPIKVG SQ RGVMLEALGLKVFNVVGPRKGKHAPELLVKAYKSVFANSGVALTPLISVGIFSVPLEESLSAFLACVGDRHCKCFCYGDK SQ EREAIIKYMDGLVDAIFKEALVDTTPVQEDVQQVSQKPVLPNFEPFRIEGAHAFYECNPEGLMSLGADKLVLFTNSNLDF SQ CSVGKCLNDVTSGALLEAINVFKKSNKTVPAGNCVTLDCANMISITMVVLPFDGDANYDKNYARAVVKVSKLKGKLVLAV SQ DDATLYSKLSHLSVLGFVSTPDDVERFYANKSVVIKVTEDTRSVKAVKVESTATYGQQIGPCLVNDTVVTDNKPVVADVV SQ AKVVPNANWDSHYGFDKAGEFHMLDHTGFTFPSEVVNGRRVIKTTDNNCWVNVTCLQLQFARFRFKSAGLQAMWESYCTG SQ DVAMFVHWLYWLTGVDKGQPSDSENALNMLSKYIVPAGSVTIERVTHDGCCCSKRVVTAPVVNASVLKLGVEDGLCPHGL SQ NYIGKVVVVKGTTIVVNVGKPVVAPSHLFLKGVSYTTFLDNGNGVVGHYTVFDHGTGMVHDGDAFVPGDLNVSPVTNVVV SQ SEQTAVVIKDPVKKAELDATKLLDTMNYASERFFSFGDFMSRNLITVFLYILSILGLCFRAFRKRDVKVLAGVPQRTGII SQ LRKSMRYNAKALGVFFKLKLYWFKVLGKFSLGIYALYALLFMTIRFTPIGSPVCDDVVAGYANSSFDKNEYCNSVICKVC SQ LYGYQELSDFSHTQVVWQHLRDPLIGNVMPFFYLAFLAIFGGVYVKAITLYFIFQYLNSLGVFLGLQQSIWFLQLVPFDV SQ FGDEIVVFFIVTRVLMFIKHVCLGCDKASCVACSKSARLKRVPVQTIFQGTSKSFYVHANGGSKFCKKHNFFCLNCDSYG SQ PGCTFINDVIATEVGNVVKLNVQPTGPATILIDKVEFSNGFYYLYSGDTFWKYNFDITDSKYTCKEALKNCSIITDFIVF SQ NNNGSNVNQVKNACVYFSQMLCKPVKLVDSALLASLSVDFGASLHSAFVSVLSNSFGKDLSSCNDMQDCKSTLGFDDVPL SQ DTFNAAVAEAHRYDVLLTDMSFNNFTTSYAKPEEKFPVHDIATCMRVGAKIVNHNVLVKDSIPVVWLVRDFIALSEETRK SQ YIIRTTKVKGITFMLTFNDCRMHTTIPTVCIANKKGAGLPSFSKVKKFFWFLCLFIVAAFFALSFLDFSTQVSSDSDYDF SQ KYIESGQLKTFDNPLSCVHNVFINFDQWHDAKFGFTPVNNPSCPIVVGVSDEARTVPGIPAGVYLAGKTLVFAINTIFGT SQ SGLCFDASGVADKGACIFNSACTTLSGLGGTAVYCYKNGLVEGAKLYSELAPHSYYKMVDGNAVSLPEIISRGFGIRTIR SQ TKAMTYCRVGQCVQSAEGVCFGADRFFVYNAESGSDFVCGTGLFTLLMNVISVFSKTVPVTVLSGQILFNCIIAFVAVAV SQ CFLFTKFKRMFGDMSVGVFTVGACTLLNNVSYIVTQNTLGMLGYATLYFLCTKGVRYMWIWHLGFLISYILIAPWWVLMV SQ YAFSAIFEFMPNLFKLKVSTQLFEGDKFVGSFENAAAGTFVLDMHAYERLANSISTEKLRQYASTYNKYKYYSGSASEAD SQ YRLACFAHLAKAMMDYASNHNDTLYTPPTVSYNSTLQAGLRKMAQPSGVVEKCIVRVCYGNMALNGLWLGDIVMCPRHVI SQ ASSTTSTIDYDYALSVLRLHNFSISSGNVFLGVVSATMRGALLQIKVNQNNVHTPKYTYRTVRPGESFNILACYDGAAAG SQ VYGVNMRSNYTIRGSFINGACGSPGYNINNGTVEFCYLHQLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGASSLFTENV SQ LAFLYAALINGSTWWLSSSRIAVDRFNEWAVHNGMTTVGNTDCFSILAAKTGVDVQRLLASIQSLHKNFGGKQILGHTSL SQ TDEFTTGEVVRQMYGVNLQGGYVSRACRNVLLVGSFLTFFWSELVSYTKFFWVNPGYVTPMFACLSLLSSLLMFTLKHKT SQ LFFQVFLIPALIVTSCINLAFDVEVYNYLAEHFDYHVSLMGFNAQGLVNIFVCFVVTILHGTYTWRFFNTPASSVTYVVA SQ LLTAAYNYFYASDILSCAMTLFASVTGNWFVGAVCYKVAVYMALRFPTFVAIFGDIKSVMFCYLVLGYFTCCFYGILYWF SQ NRFFKVSVGVYDYTVSAAEFKYMVANGLRAPTGTLDSLLLSAKLIGIGGERNIKISSVQSKLTDIKCSNVVLLGCLSSMN SQ VSANSTEWAYCVDLHNKINLCNDPEKAQEMLLALLAFFLSKNSAFGLDDLLESYFNDNSMLQSVASTYVGLPSYVIYENA SQ RQQYEDAVNNGSPPQLVKQLRHAMNVAKSEFDREASTQRKLDRMAEQAAAQMYKEARAVNRKSKVVSAMHSLLFGMLRRL SQ DMSSVDTILNLAKDGVVPLSVIPAVSATKLNIVTSDIDSYNRIQREGCVHYAGTIWNIIDIKDNDGKVVHVKEVTAQNAE SQ SLSWPLVLGCERIVKLQNNEIIPGKLKQRSIKAEGDGIVGEGKALYNNEGGRTFMYAFISDKPDLRVVKWEFDGGCNTIE SQ LEPPRKFLVDSPNGAQIKYLYFVRNLNTLRRGAVLGYIGATVRLQAGKQTEQAINSSLLTLCAFAVDPAKTYIDAVKSGH SQ KPVGNCVKMLANGSGNGQAVTNGVEASTNQDSYGGASVCLYCRAHVEHPSMDGFCRLKGKYVQVPLGTVDPIRFVLENDV SQ CKVCGCWLSNGCTCDRSIMQSTDMAYLNRVRGSSAARLEPCNGTDTQHVYRAFDIYNKDVACLGKFLKVNCVRLKNLDKH SQ DAFYVVKRCTKSAMEHEQSIYSRLEKCGAIAEHDFFTWKDGRAIYGNVCRKDLTEYTMMDLCYALRNFDENNCDVLKSIL SQ IKVGACEESYFNNKVWFDPVENEDIHRVYALLGTIVARAMLKCVKFCDAMVEQGIVGVVTLDNQDLNGDFYDFGDFTCSI SQ KGMGVPICTSYYSYMMPVMGMTNCLASECFVKSDIFGEDFKSYDLLEYDFTEHKTALFNKYFKYWGLQYHPNCVDCSDEQ SQ CIVHCANFNTLFSTTIPITAFGPLCRKCWIDGVPLVTTAGYHFKQLGIVWNNDLNLHSSRLSINELLQFCSDPALLIASS SQ PALVDQRTVCFSVAALGTGMTNQTVKPGHFNKEFYDFLLEQGFFSEGSELTLKHFFFAQKVDAAVKDFDYYRYNRPTVLD SQ ICQARVVYQIVQRYFDIYEGGCITAKEVVVTNLNKSAGYPLNKFGKAGLYYESLSYEEQDELYAYTKRNILPTMTQLNLK SQ YAISGKERARTVGGVSLLSTMTTRQYHQKHLKSIVNTRGASVVIGTTKFYGGWDNMLKNLIDGVENPCLMGWDYPKCDRA SQ LPNMIRMISAMILGSKHTTCCSSTDRFFRLCNELAQVLTEVVYSNGGFYLKPGGTTSGDATTAYANSVFNIFQAVSANVN SQ KLLSVDSNVCHNLEVKQLQRKLYECCYRSTIVDDQFVVEYYGYLRKHFSMMILSDDGVVCYNNDYASLGYVADLNAFKAV SQ LYYQNNVFMSASKCWIEPDINKGPHEFCSQHTMQIVDKEGTYYLPYPDPSRILSAGVFVDDVVKTDAVVLLERYVSLAID SQ AYPLSKHENPEYKKVFYVLLDWVKHLYKTLNAGVLESFSVTLLEDSTAKFWDESFYANMYEKSAVLQSAGLCVVCGSQTV SQ LRCGDCLRRPMLCTKCAYDHVIGTTHKFILAITPYVCCASDCGVNDVTKLYLGGLSYWCHEHKPRLAFPLCSAGNVFGLY SQ KNSATGSPDVEDFNRIATSDWTDVSDYRLANDVKDSLRLFAAETIKAKEESVKSSYACATLHEVVGPKELLLKWEVGRPK SQ PPLNRNSVFTCYHITKNTKFQIGEFVFEKAEYDNDAVTYKTTATTKLVPGMVFVLTSHNVQPLRAPTIANQERYSTIHKL SQ HPAFNIPEAYSSLVPYYQLIGKQKITTIQGPPGSGKSHCVIGLGLYYPGARIVFTACSHAAVDSLCVKASTAYSNDKCSR SQ IIPQRARVECYDGFKSNNTSAQYLFSTVNALPECNADIVVVDEVSMCTNYDLSVINQRISYRHVVYVGDPQQLPAPRVMI SQ SRGTLEPKDYNVVTQRMCALKPDVFLHKCYRCPAEIVRTVSEMVYENQFIPVHPDSKQCFKIFCKGNVQVDNGSSINRRQ SQ LDVVRMFLAKNPRWSKAVFISPYNSQNYVASRLLGLQIQTVDSSQGSEYDYVIYAQTSDTAHASNVNRFNVAITRAKKGI SQ LCIMCDRSLFDLLKFFELKLSDLQANEGCGLFKDCSRGDDLLPPSHANTFMSLADNFKTDQYLAVQIGVNGPIKYEHVIS SQ FMGFRFDINIPNHHTLFCTRDFAMRNVRGWLGFDVEGAHVVGSNVGTNVPLQLGFSNGVDFVVRPEGCVVTESGDYIKPV SQ RARAPPGEQFAHLLPLLKRGQPWDVVRKRIVQMCSDYLANLSDILIFVLWAGGLELTTMRYFVKIGPSKSCDCGKVATCY SQ NSALHTYCCFKHALGCDYLYNPYCIDIQQWGYKGSLSLNHHEHCNVHRNEHVASGDAIMTRCLAIHDCFVKNVDWSITYP SQ FIGNEAVINKSGRIVQSHTMRSVLKLYNPKAIYDIGNPKGIRCAVTDAKWFCFDKNPTNSNVKTLEYDYITHGQFDGLCL SQ FWNCNVDMYPEFSVVCRFDTRCRSPLNLEGCNGGSLYVNNHAFHTPAFDKRAFAKLKPMPFFFYDDTECDKLQDSINYVP SQ LRASNCITKCNVGGAVCSKHCAMYHSYVNAYNTFTSAGFTIWVPTSFDTYNLWQTFSNNLQGLENIAFNVLKKGSFVGDE SQ GELPVAVVNDKVLVRDGTVDTLVFTNKTSLPTNVAFELYAKRKVGLTPPITILRNLGVVCTSKCVIWDYEAERPLTTFTK SQ DVCKYTDFEGDVCTLFDNSIVGSLERFSMTQNAVLMSLTAVKKLTGIKLTYGYLNGVPVNTHEDKPFTWYIYTRKNGKFE SQ DYPDGYFTQGRTTADFSPRSDMEKDFLSMDMGLFINKYGLEDYGFEHVVYGDVSKTTLGGLHLLISQVRLACMGVLKIDE SQ FVSSNDSTLKSCTVTYADNPSSKMVCTYMDLLLDDFVSILKSLDLSVVSKVHEVMVDCKMWRWMLWCKDHKLQTFYPQLQ SQ ASEWKCGYSMPSIYKIQRMCLEPCNLYNYGAGVKLPDGIMFNVVKYTQLCQYLNSTTMCVPHHMRVLHLGAGSDKGVAPG SQ TAVLRRWLPLDAIIVDNDSVDYVSDADYSVTGDCSTLYLSDKFDLVISDMYDGKIKSCDGENVSKEGFFPYINGVITEKL SQ ALGGTVAIKVTEFSWNKKLYELIQKFEYWTMFCTSVNTSSSEAFLIGVHYLGDFASGAVIDGNTMHANYIFWRNSTIMTM SQ SYNSVLDLSKFNCKHKATVVVNLKDSSISDVVLGLLKNGKLLVRNNDAICGFSNHLVNVNK //