ID  Q04561;
PN  Non-structural protein 12;
GN  rep;
OS  11049;
SL  Nucleus Position: SL-0382;
SL  Comments: [Nsp1]: Host nucleus {ECO:0000269|PubMed:23287061}. Host cytoplasm {ECO:0000269|PubMed:23287061}. [Nsp1-alpha papain-like cysteine proteinase]: Host nucleus {ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:28235682}. Host cytoplasm {ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:28235682}. [Nsp1-beta papain-like cysteine proteinase]: Host nucleus {ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:28235682}. [Nsp2 cysteine proteinase]: Host cytoplasm {ECO:0000269|PubMed:28648849}. Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Non-structural protein 5-6-7]: Host endoplasmic reticulum {ECO:0000269|PubMed:21799305}. Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}. [Serine protease nsp4]: Host cytoplasm {ECO:0000305}. [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000269|PubMed:25449571}. Host cytoplasm, host perinuclear region {ECO:0000305}. [Helicase nsp10]: Host cytoplasm {ECO:0000269|PubMed:28648849}. Host cytoplasm, host perinuclear region {ECO:0000305}. [Uridylate-specific endoribonuclease nsp11]: Host cytoplasm {ECO:0000269|PubMed:29444948}. Host nucleus {ECO:0000269|PubMed:29444948}. [Non-structural protein 12]: Host cytoplasm {ECO:0000269|PubMed:29920289}.
DR  UNIPROT: Q04561;
DR  Pfam: PF16749;
DR  Pfam: PF14757;
DR  Pfam: PF14758;
DR  Pfam: PF05410;
DR  Pfam: PF05411;
DR  Pfam: PF05412;
DR  Pfam: PF05579;
DR  Pfam: PF00680;
DR  Pfam: PF01443;
DR  PROSITE: PS51538;
DR  PROSITE: PS51961;
DR  PROSITE: PS51493;
DR  PROSITE: PS51539;
DR  PROSITE: PS51540;
DR  PROSITE: PS51652;
DR  PROSITE: PS51958;
DR  PROSITE: PS51947;
DR  PROSITE: PS51657;
DR  PROSITE: PS50507;
DE  Function: [Replicase polyprotein 1ab]: 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. [Nsp1-alpha papain-like cysteine proteinase]: Inhibits host IFN-beta production. Plays a role in the degradation of the host transcriptional activator CREBBP protein. The degradation of host CREBBP which is a key component of the IFN enhanceosome is likely responsible for the inhibition of interferon mediated by Nsp1-alpha. Participates also in the inhibition of host NF-kappa-B activation by counteracting LUBAC-dependent induction of NF-kappa-B. Reduces host NEMO ubiquitination by blocking the interaction between the two LUBAC complex components RNF31 and SHARPIN. {ECO:0000250|UniProtKB:Q9WJB2, ECO:0000269|PubMed:23287061, ECO:0000269|PubMed:27881655}. [Nsp1-beta papain-like cysteine proteinase]: Plays a role in blocking host mRNA nuclear export to the cytoplasm and subversion of host protein synthesis (PubMed:28235682). Additionally, inhibits the interferon-activated JAK/STAT signal transduction by mediating the ubiquitination and subsequent proteasomal degradation of host KPNA1. {ECO:0000250|UniProtKB:Q9WJB2, ECO:0000269|PubMed:28235682}. [Nsp2 cysteine proteinase]: Multifunctional protein that acts as a viral protease and as a viral antagonist of host immune response. Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays deubiquitinating activity that cleaves both ubiquitinated and ISGylated products and therefore inhibits ubiquitin and ISG15-dependent host innate immunity. Deubiquitinates also host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation. {ECO:0000250|UniProtKB:A0MD28}. [Non-structural protein 3]: Plays a role in the inhibition of the immune response by interacting with host IFITM1. This interaction leads to the proteasomal degradation of the IFN-induced antiviral protein IFITM1. {ECO:0000269|PubMed:25102331}. [Serine protease nsp4]: Cleaves the majority of cleavage sites present in the C-terminus of the polyprotein. Triggers host apoptosis through caspase-3, -8, and -9 activations. Subverts host innate immune responses through its protease activity. Targets the NF- kappa-B essential modulator NEMO and mediates its cleavage (PubMed:25008936). Blocks host interferon beta induction and downstream signaling by cleaving mitochondrial MAVS, dislodging it from the mitochondria (PubMed:27329948). Impairs host defense by cleaving host mRNA-decapping enzyme DCP1A to attenuate its antiviral activity (PubMed:30158128). {ECO:0000269|PubMed:19646449, ECO:0000269|PubMed:23936003, ECO:0000269|PubMed:25008936, ECO:0000269|PubMed:27329948, ECO:0000269|PubMed:30158128}. [Non-structural protein 5-6-7]: Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. {ECO:0000269|PubMed:21799305}. [Non-structural protein 5]: Plays a role in the inhibition of host STAT3 signaling pathway by inducing the degradation of STAT3. {ECO:0000269|PubMed:27881658}. [RNA-directed RNA polymerase]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000269|PubMed:25449571}. [Helicase nsp10]: Displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000269|PubMed:12127789}. [Uridylate-specific endoribonuclease nsp11]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, PKR (By similarity) and NLRP3 inflammasome (PubMed:26398903). 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). Also plays a role in the inhibition of host type I interferon production by recruiting host OTULIN to promote removal of linear ubiquitination targeting host NEMO (PubMed:29444948). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000250|UniProtKB:P19811, ECO:0000269|PubMed:26398903, ECO:0000269|PubMed:29444948}.
DE  Reference Proteome: Yes;
DE  Interaction: A5D9M6; IntAct: EBI-11702011; Score: 0.40
DE  Interaction: A0A068CA64; IntAct: EBI-11702092; Score: 0.40
GO  GO:0030430;
GO  GO:0044165;
GO  GO:0033644;
GO  GO:0042025;
GO  GO:0044220;
GO  GO:0016021;
GO  GO:0005524;
GO  GO:0016887;
GO  GO:0004843;
GO  GO:0004197;
GO  GO:0003678;
GO  GO:0004519;
GO  GO:0004521;
GO  GO:0016829;
GO  GO:0003723;
GO  GO:0003724;
GO  GO:0003968;
GO  GO:0004252;
GO  GO:0008270;
GO  GO:0006351;
GO  GO:0039520;
GO  GO:0039648;
GO  GO:0006508;
GO  GO:0039579;
GO  GO:0039514;
GO  GO:0039563;
GO  GO:0039522;
GO  GO:0039644;
GO  GO:0039502;
GO  GO:0039545;
GO  GO:0019082;
GO  GO:0039694;
TP  Membrane Topology: Transmembrane; Source: UniProt - Sequence Analysis {ECO:0000255};
SQ  MSGTFSRCMCTPAARVFWNAGQVFCTRCLSARSLLSPELQDTDLGAVGLFYKPRDKLHWKVPIGIPQVECTPSGCCWLSA
SQ  VFPLARMTSGNHNFLQRLVKVADVLYRDGCLAPRHLRELQVYERGCNWYPITGPVPGMGLFANSMHVSDQPFPGATHVLT
SQ  NSPLPQQACRQPFCPFEEAHSSVYRWKKFVVFTDSSLNGRSRMMWTPESDDSAALEVLPPELERQVEILIRSFPAHHPVD
SQ  LADWELTESPENGFSFNTSHSCGHLVQNPDVFDGKCWLSCFLGQSVEVRCHEEHLADAFGYQTKWGVHGKYLQRRLQVRG
SQ  IRAVVDPDGPIHVEALSCPQSWIRHLTLDDDVTPGFVRLTSLRIVPNTEPTTSRIFRFGAHKWYGAAGKRARAKRAAKSE
SQ  KDSAPTPKVALPVPTCGITTYSPPTDGSCGWHVLAAIMNRMINGDFTSPLTQYNRPEDDWASDYDLVQAIQCLRLPATVV
SQ  RNRACPNAKYLIKLNGVHWEVEVRSGMAPRSLSRECVVGVCSEGCVAPPYPADGLPKRALEALASAYRLPSDCVSSGIAD
SQ  FLANPPPQEFWTLDKMLTSPSPERSGFSSLYKLLLEVVPQKCGATEGAFIYAVERMLKDCPSSKQAMALLAKIKVPSSKA
SQ  PSVSLDECFPTDVLADFEPASQERPQSSGAAVVLCSPDAKEFEEAAPEEVQESGHKAVHSALLAEGPNNEQVQVVAGEQL
SQ  KLGGCGLAVGNAHEGALVSAGLINLVGGNLSPSDPMKENMLNSREDEPLDLSQPAPASTTTLVREQTPDNPGSDAGALPV
SQ  TVREFVPTGPILCHVEHCGTESGDSSSPLDLSDAQTLDQPLNLSLAAWPVRATASDPGWVHGRREPVFVKPRNAFSDGDS
SQ  ALQFGELSESSSVIEFDRTKDAPVVDAPVDLTTSNEALSVVDPFEFAELKRPRFSAQALIDRGGPLADVHAKIKNRVYEQ
SQ  CLQACEPGSRATPATREWLDKMWDRVDMKTWRCTSQFQAGRILASLKFLPDMIQDTPPPVPRKNRASDNAGLKQLVAQWD
SQ  RKLSVTPPPKPVGPVLDQIVPPPTDIQQEDVTPSDGPPHAPDFPSRVSTGGSWKGLMLSGTRLAGSISQRLMTWVFEVFS
SQ  HLPAFMLTLFSPRGSMAPGDWLFAGVVLLALLLCRSYPILGCLPLLGVFSGSLRRVRLGVFGSWMAFAVFLFSTPSNPVG
SQ  SSCDHDSPECHAELLALEQRQLWEPVRGLVVGPSGLLCVILGKLLGGSRYLWHVLLRLCMLADLALSLVYVVSQGRCHKC
SQ  WGKCIRTAPAEVALNVFPFSRATRVSLVSLCDRFQTPKGVDPVHLATGWRGCWRGESPIHQPHQKPIAYANLDEKKMSAQ
SQ  TVVAVPYDPSQAIKCLKVLQAGGAIVDQPTPEVVRVSEIPFSAPFFPKVPVNPDCRVVVDSDTFVAAVRCGYSTAQLVLG
SQ  RGNFAKLNQTPPRNSISTKTTGGASYTLAVAQVSAWTLVHFILGLWFTSPQVCGRGTADPWCSNPFSYPTYGPGVVCSSR
SQ  LCVSADGVTLPLFSAVAQLSGREVGIFILVLVSLTALAHRMALKADMLVVFSAFCAYAWPMSSWLICFFPILLKWVTLHP
SQ  LTMLWVHSFLVFCLPAAGILSLGITGLLWAIGRFTQVAGIITPYDIHQYTSGPRGAAAVATAPEGTYMAAVRRAALTGRT
SQ  LIFTPSAVGSLLEGAFRTHKPCLNTVNVVGSSLGSGGVFTIDGRRTVVTAAHVLNGDTARVTGDSYNRMHTFKTNGDYAW
SQ  SHADDWQGVAPVVKVAKGYRGRAYWQTSTGVEPGIIGEGFAFCFTNCGDSGSPVISESGDLIGIHTGSNKLGSGLVTTPE
SQ  GETCTIKETKLSDLSRHFAGPSVPLGDIKLSPAIIPDVTSIPSDLASLLASVPVVEGGLSTVQLLCVFFLLWRMMGHAWT
SQ  PIVAVGFFLLNEILPAVLVRAVFSFALFVLAWATPWSAQVLMIRLLTASLNRNKLSLAFYALGGVVGLAAEIGTFAGRLS
SQ  ELSQALSTYCFLPRVLAMTSCVPTIIIGGLHTLGVILWLFKYRCLHNMLVGDGSFSSAFFLRYFAEGNLRKGVSQSCGMN
SQ  NESLTAALACKLSQADLDFLSSLTNFKCFVSASNMKNAAGQYIEAAYAKALRQELASLVQIDKMKGVLSKLEAFAETATP
SQ  SLDIGDVIVLLGQHPHGSILDINVGTERKTVSVQETRSLGGSKFSVCTVVSNTPVDALTGIPLQTPTPLFENGPRHRSEE
SQ  DDLKVERMKKHCVSLGFHNINGKVYCKIWDKSTGDTFYTDDSRYTQDHAFQDRSADYRDRDYEGVQTTPQQGFDPKSETP
SQ  VGTVVIGGITYNRYLIKGKEVLVPKPDNCLEAAKLSLEQALAGMGQTCDLTAAEVEKLKRIISQLQGLTTEQALNCLLAA
SQ  SGLTRCGRGGLVVTETAVKIIKYHSRTFTLGPLDLKVTSEVEVKKSTEQGHAVVANLCSGVILMRPHPPSLVDVLLKPGL
SQ  DTIPGIQPGHGAGNMGVDGSIWDFETAPTKAELELSKQIIQACEVRRGDAPNLQLPYKLYPVRGDPERHKGRLINTRFGD
SQ  LPYKTPQDTKSAIHAACCLHPNGAPVSDGKSTLGTTLQHGFELYVPTVPYSVMEYLDSRPDTPFMCTKHGTSKAAAEDLQ
SQ  KYDLSTQGFVLPGVLRLVRRFIFGHIGKAPPLFLPSTYPAKNSMAGINGQRFPTKDVQSIPEIDEMCARAVKENWQTVTP
SQ  CTLKKQYCSKPKTRTILGTNNFIALAHRSALSGVTQAFMKKAWKSPIALGKNKFKELHCTVAGRCLEADLASCDRSTPAI
SQ  VRWFVANLLYELAGCEEYLPSYVLNCCHDLVATQDGAFTKRGGLSSGDPVTSVSNTVYSLVIYAQHMVLSALKMGHEIGL
SQ  KFLEEQLKFEDLLEIQPMLVYSDDLVLYAERPTFPNYHWWVEHLDLMLGFRTDPKKTVITDKPSFLGCRIEAGRQLVPNR
SQ  DRILAALAYHMKAQNASEYYASAAAILMDSCACIDHDPEWYEDLICGIARCARQDGYSFPGPAFFMSMWEKLRSHNEGKK
SQ  FRHCGICDAKADYASACGLDLCLFHSHFHQHCPVTLSCGHHAGSKECSQCQSPVGAGRSPLDAVLKQIPYKPPRTVIMKV
SQ  GNKTTALDPGRYQSRRGLVAVKRGIAGNEVDLSDGDYQVVPLLPTCKDINMVKVACNVLLSKFIVGPPGSGKTTWLLSQV
SQ  QDDDVIYTPTHQTMFDIVSALKVCRYSIPGASGLPFPPPARSGPWVRLIASGHVPGRVSYLDEAGYCNHLDILRLLSKTP
SQ  LVCLGDLQQLHPVGFDSYCYVFDQMPQKQLTTIYRFGPNICAAIQPCYREKLESKARNTRVVFTTRPVAFGQVLTPYHKD
SQ  RIGSAITIDSSQGATFDIVTLHLPSPKSLNKSRALVAITRARHGLFIYDPHNQLQEFFNLTPERTDCNLVFSRGDELVVL
SQ  NADNAVTTVAKALETGPSRFRVSDPRCKSLLAACSASLEGSCMPLPQVAHNLGFYFSPDSPTFAPLPKELAPHWPVVTHQ
SQ  NNRAWPDRLVASMRPIDARYSKPMVGAGYVVGPSTFLGTPGVVSYYLTLYIRGEPQALPETLVSTGRIATDCREYLDAAE
SQ  EEAAKELPHAFIGDVKGTTVGGCHHITSKYLPRSLPKDSVAVVGVSSPGRAAKAVCTLTDVYLPELRPYLQPETASKCWK
SQ  LKLDFRDVRLMVWKGATAYFQLEGLTWSALPDYARFIQLPKDAVVYIDPCIGPATANRKVVRTTDWRADLAVTPYDYGAQ
SQ  NILTTAWFEDLGPQWKILGLQPFRRAFGFENTEDWAILARRMNDGKDYTDYNWNCVRERPHAIYGRARDHTYHFAPGTEL
SQ  QVELGKPRLPPGQVP
//