ID   POLN_RUBVR              Reviewed;        2116 AA.
AC   O40955;
DT   13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 110.
DE   RecName: Full=Non-structural polyprotein p200;
DE            Short=p200;
DE   Contains:
DE     RecName: Full=Protease/methyltransferase p150;
DE              Short=p150;
DE              EC=3.4.22.-;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase p90;
DE              Short=p90;
DE              EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE              EC=3.6.1.15;
DE              EC=3.6.4.13;
OS   Rubella virus (strain RA27/3 vaccine) (RUBV).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC   Hepelivirales; Matonaviridae; Rubivirus; Rubivirus rubellae.
OX   NCBI_TaxID=11044;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9229006; DOI=10.1007/s007050050150;
RA   Pugachev K.V., Abernathy E.S., Frey T.K.;
RT   "Genomic sequence of the RA27/3 vaccine strain of rubella virus.";
RL   Arch. Virol. 142:1165-1180(1997).
CC   -!- FUNCTION: [Non-structural polyprotein p200]: Probable principal
CC       replicase for the negative-strand DNA, which replicates the 40S (+)
CC       genomic RNA into (-) antigenomic RNA. It cannot replicate the (-) into
CC       (+) until cleaved into p150 and p90 mature proteins.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- FUNCTION: [Protease/methyltransferase p150]: Protease that cleaves the
CC       precursor polyprotein into two mature products. Together with RNA-
CC       directed RNA polymerase p90, replicates the 40S genomic and antigenomic
CC       RNA by recognizing replications specific signals. The heterodimer
CC       P150/p90 is probably the principal replicase for positive-strand
CC       genomic RNA and the 24S subgenomic RNA, which codes for structural
CC       proteins. Responsible for the mRNA-capping of the viral mRNAs. This
CC       function is necessary since all viral RNAs are synthesized in the
CC       cytoplasm, and host capping enzymes are restricted to the nucleus.
CC       Forms fibers late in the infection that may be involved in cell-to-cell
CC       spread of the virus RNA in the absence of virus particle formation.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase p90]: Together with
CC       protease/methyltransferase p150, replicates the 40S genomic and
CC       antigenomic RNA by recognizing replications specific signals. The
CC       heterodimer P150/p90 is probably the principal replicase for positive-
CC       strand genomic RNA and the 24S subgenomic RNA, which codes for
CC       structural proteins. A helicase activity is probably also present.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC         COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC         EC=2.7.7.48; Evidence={ECO:0000250|UniProtKB:Q86500,
CC         ECO:0000255|PROSITE-ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC         Evidence={ECO:0000250|UniProtKB:Q86500};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000250|UniProtKB:Q86500};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU01237};
CC       Note=Zn(2+) is necessary for the protease activity. The protease can
CC       also function efficiently with Cd(2+) and Co(2+). {ECO:0000255|PROSITE-
CC       ProRule:PRU01237};
CC   -!- SUBUNIT: [Protease/methyltransferase p150]: Interacts with RNA-directed
CC       RNA polymerase p90. Interacts with host CALM1; this interaction is
CC       necessary for the protease activity and viral infectivity. Interacts
CC       with host C1QBP. Interacts with the capsid protein.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- SUBUNIT: [RNA-directed RNA polymerase p90]: Interacts with human
CC       RB1/retinoblastoma protein. Interacts with protease/methyltransferase
CC       p150. {ECO:0000250|UniProtKB:Q86500}.
CC   -!- INTERACTION:
CC       PRO_0000240177; Q07021: C1QBP; Xeno; NbExp=2; IntAct=EBI-6383633, EBI-347528;
CC       PRO_0000240177; Q9MZE0: C1QBP; Xeno; NbExp=5; IntAct=EBI-6383633, EBI-6375765;
CC   -!- SUBCELLULAR LOCATION: [Non-structural polyprotein p200]: Host membrane
CC       {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q86500}. Note=Localizes to cytoplasmic foci at
CC       24 hpi. {ECO:0000250|UniProtKB:Q86500}.
CC   -!- SUBCELLULAR LOCATION: [Protease/methyltransferase p150]: Host membrane
CC       {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm, host perinuclear region
CC       {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q86500}. Note=At 36 hpi, localizes to the host
CC       cytoplasm, probably in vesicles inside host vacuoles of endosomal and
CC       lysosomal origin (By similarity). At 72 hpi, localizes to filamentous
CC       structures in the host cytoplasm (By similarity).
CC       {ECO:0000250|UniProtKB:P13889, ECO:0000250|UniProtKB:Q86500}.
CC   -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase p90]: Host membrane
CC       {ECO:0000250|UniProtKB:Q86500}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:Q86500}. Note=Localizes to the cytoplasm and to
CC       the cytoplasmic fibers formed by protease/methyltransferase p150.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- DOMAIN: [Protease/methyltransferase p150]: The N-terminus has a
CC       methyltransferase activity for mRNA-capping. The C-terminus harbors a
CC       protease active in cis or in trans which specifically cleaves and
CC       releases the two mature proteins. Both the N-terminus and C-terminus
CC       are required for fiber formation. The N-terminus is involved in
CC       associating with membranes. An EF-hand Ca(2+)-binding motif is present
CC       in the protease. Also contains 3 SH3-binding motifs that are
CC       responsible for the interaction with host C1QBP.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- PTM: [Non-structural polyprotein p200]: Specific enzymatic cleavage by
CC       its own cysteine protease yield mature proteins p150 and p90.
CC       {ECO:0000250|UniProtKB:Q86500}.
CC   -!- MISCELLANEOUS: Rubella virus in utero infection has frequently severe
CC       consequences on normal fetal development, collectively known as
CC       congenital rubella syndrome (CRS). The teratogenicity of the virus is
CC       possibly due to the interaction between the p90 protein and the human
CC       RB1/retinoblastoma protein. {ECO:0000250|UniProtKB:Q86500}.
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DR   EMBL; L78917; AAB81187.1; -; Genomic_RNA.
DR   SMR; O40955; -.
DR   IntAct; O40955; 5.
DR   MEROPS; C27.001; -.
DR   PRIDE; O40955; -.
DR   Proteomes; UP000007188; Genome.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0006396; P:RNA processing; IEA:InterPro.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   CDD; cd21557; Macro_X_Nsp3-like; 1.
DR   Gene3D; 3.40.220.10; -; 1.
DR   Gene3D; 3.40.50.300; -; 1.
DR   InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR   InterPro; IPR002588; Alphavirus-like_MT_dom.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR043472; Macro_dom-like.
DR   InterPro; IPR044371; Macro_X_NSP3-like.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR008738; Peptidase_C27.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR022245; Rubi_NSP_C.
DR   InterPro; IPR044070; RUBV_NS_PRO.
DR   InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF05407; Peptidase_C27; 1.
DR   Pfam; PF00978; RdRP_2; 1.
DR   Pfam; PF12601; Rubi_NSP_C; 1.
DR   Pfam; PF01443; Viral_helicase1; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   SUPFAM; SSF52949; SSF52949; 1.
DR   SUPFAM; SSF56672; SSF56672; 1.
DR   PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR   PROSITE; PS51154; MACRO; 1.
DR   PROSITE; PS51657; PSRV_HELICASE; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51889; RUBV_NS_PRO; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Calcium; Helicase; Host cytoplasm; Host membrane; Hydrolase;
KW   Membrane; Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW   Protease; RNA-directed RNA polymerase; Thiol protease; Transferase;
KW   Viral RNA replication; Zinc.
FT   CHAIN           1..2116
FT                   /note="Non-structural polyprotein p200"
FT                   /id="PRO_0000240176"
FT   CHAIN           1..1301
FT                   /note="Protease/methyltransferase p150"
FT                   /id="PRO_0000240177"
FT   CHAIN           1302..2116
FT                   /note="RNA-directed RNA polymerase p90"
FT                   /id="PRO_0000240178"
FT   DOMAIN          57..247
FT                   /note="Alphavirus-like MT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT   DOMAIN          806..985
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1000..1301
FT                   /note="Peptidase C27"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   DOMAIN          1320..1468
FT                   /note="(+)RNA virus helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          1469..1609
FT                   /note="(+)RNA virus helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          1870..1981
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          36..49
FT                   /note="Required for efficient proteolysis and P150-P90
FT                   interaction"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   REGION          712..782
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          992..1031
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1152..1183
FT                   /note="Interaction with host CALM1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   REGION          1193..1228
FT                   /note="EF-hand-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   REGION          1700..1900
FT                   /note="Involved in P150-P90 interaction"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   MOTIF           727..732
FT                   /note="PxxPxR; class II SH3-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   MOTIF           747..752
FT                   /note="PxxPxR; class II SH3-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   MOTIF           761..766
FT                   /note="PxxPxR; class II SH3-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   MOTIF           1902..1906
FT                   /note="Human RB1 binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q86500"
FT   COMPBIAS        747..772
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1152
FT                   /note="For cysteine protease activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   ACT_SITE        1273
FT                   /note="For cysteine protease activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   BINDING         1175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   BINDING         1178
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   BINDING         1227
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   BINDING         1273
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
FT   BINDING         1352..1359
FT                   /ligand="a ribonucleoside 5'-triphosphate"
FT                   /ligand_id="ChEBI:CHEBI:61557"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   SITE            1301..1302
FT                   /note="Cleavage; autocatalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01237"
SQ   SEQUENCE   2116 AA;  230322 MW;  28F6A48BBA8CD97D CRC64;
     MERLLDEVLA PGGPYNLTVG SWVRDHVRSI VEGAWEVRDV VSAAQKRAIV AVIPRPVFTQ
     MQVSDHPALH AISRYTRRHW IEWGPKEALH VLIDPSPGLL REVARVERRW VALCLHRTAR
     KLATALAETA SEAWHADYVC ALRGAPSGPF YVHPEDVPHG GRAVADRCLL YYTPMQMCEL
     MRTIDATLLV AVDLWPVALA AHVGDDWDDL GIAWHLDHDG GCPADCRGAG AGPTPGYTRP
     CTTRIYQVLP DTAHPGRLYR CGPRLWTRDC AVAELSWEVA QHCGHQARVR AVRCTLPIRH
     VRSLQPSARV RLPDLVHLAE VGRWRWFSLP RPVFQRMLSY CKTLSPDAYY SERVFKFKNA
     LSHSITLAGN VLQEGWKGTC AEEDALCAYV AFRAWQSNAR LAGIMKSAKR CAADSLSVAG
     WLDTIWGAIK RFFGSVPLAE RMEEWEQDAA VAAFDRGPLE DGGRHLDTVQ PPKSPPRPEI
     AATWIVHAAS ADRHCACAPR CDVPRERPSA PAGPPDDEAL IPPWLFAEHR ALRCREWDFE
     VLRARADTAA APAPLAPRPA RYPTVLYRHP AHHGPWLTLD EPGEADAALV LCDPLGQPLR
     GPERHFAAGA HMCAQARGLQ AFVRVVPPPE RPWADGGARA WAKFFRGCAW AQRLLGEPAV
     MHLPYTDGDV PQLIALALRT LAQQGAALAL SVRDLPGGAA FDANAVTAAV RAGPGQSAAT
     SSPPGDPPPP RCARRSQRHS DARGTPPPAP ARDPPPPAPS PPAPPRAGDP VPPTSAGPAD
     RARDAELEVA YEPSGPPTST KADPDSDIVE SYARAAGPVH LRVRDIMDPP PGCKVVVNAA
     NEGLLAGSGV CGAIFANATA ALAADCRRLA PCPTGEAVAT PGHGCGYTHI IHAVAPRRPR
     DPAALEEGEA LLERAYRSIV ALAAARRWAR VACPLLGAGV YGWSAAESLR AALAATRTEP
     AERVSLHICH PDRATLTHAS VLVGAGLAAR RVSPPPTEPL ASCPAGDPGR PAQRSASPPA
     TPLGDATAPE PRGCQGCELC RYTRVTNDRA YVNLWLERDR GATSWAMRIP EVVVYGPEHL
     ATHFPLNHYS VLKPAEVRPP RGMCGSDMWR CRGWQGVPQV RCTPSNAHAA LCRTGVPPRV
     STRGGELDPN TCWLRAAANV AQAARACGAY TSAGCPRCAY GRALSEARTH KDFAALSQRW
     SASHADASSD GTGDPLDPLM ETVGCACSRV WVGSEHEAPP DHLLVSLHRA PNGPWGVVLE
     VRARPEGGNP TGHFVCAVGG GPRRVSDRPH LWLAVPLSRG GGTCAATDEG LAQAYYDDLE
     VRRLGDDAMA RAALASVQRP RKGPYNIRVW NMAAGAGKTT RILAAFTRED LYVCPTNALL
     HEIQAKLRAR DIEIKNAATY ERALTKPLAA YRRIYIDEAF TLGGEYCAFV ASQTTAEVIC
     VGDRDQCGPH YANNCRTPVP DRWPTERSRH TWRFPDCWAA RLRAGLDYDI EGERTGTFAC
     NLWDGRQVDL HLAFSRETVR RLHEAGIRAY TVREAQGMSV GTACIHVGRD GTDVALALTR
     DLAIVSLTRA SDALYLHELE DGSLRAAGLS AFLDAGALAE LKEVPAGIDR VVAVEQAPPP
     LPPADGIPEA QDVPPFCPRT LEELVFGRAG HPHYADLNRV TEGEREVRYM RISRHLLNKN
     HTEMPGTERV LSAVCAVRRY RAGEDGSTLR TAVARQHPRP FRQIPPPRVT AGVAQEWRMT
     YLRERIDLTD VYTQMGVAAR ELTDRYARRY PEIFAGMCTA QSLSVPAFLK ATLKCVDAAL
     GPRDTEDCHA AQGKAGLEIR AWAKEWVQVM SPHFRAIQKI IMRALRPQFL VAAGHTEPEV
     DAWWQAHYTT NAIEVDFTEF DMNQTLATRD VELEISAALL GLPCAEDYRA LRAGSYCTLR
     ELGSTETGCE RTSGEPATLL HNTTVAMCMA MRMVPKGVRW AGIFQGDDMV IFLPEGARSA
     ALKWTPAEVG LFGFHIPVKH VSTPTPSFCG HVGTAAGLFH DVMHQAIKVL CRRFDPDVLE
     EQQVALLDRL RGVYAALPDT VAANAAYYDY SAERVLAIVR ELTAYARGRG LDHPATIGAL
     EEIQTPYARA NLHDAD