POLN_RUBVM
ID POLN_RUBVM Reviewed; 2116 AA.
AC Q86500;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 130.
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.- {ECO:0000269|PubMed:12076835, ECO:0000269|PubMed:9557742};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase p90;
DE Short=p90;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539, ECO:0000269|PubMed:11437666};
DE EC=3.6.1.15 {ECO:0000269|PubMed:8599224};
DE EC=3.6.4.13;
OS Rubella virus (strain M33) (RUBV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Matonaviridae; Rubivirus; Rubivirus rubellae.
OX NCBI_TaxID=11043;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], MUTAGENESIS OF CYS-1152 AND GLY-1300,
RP PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL POLYPROTEIN P200), AND ACTIVE SITE.
RX PubMed=9656995; DOI=10.1006/viro.1998.9179;
RA Yao J., Yang D., Chong P., Hwang D., Liang Y., Gillam S.;
RT "Proteolytic processing of rubella virus nonstructural proteins.";
RL Virology 246:74-82(1998).
RN [2]
RP FUNCTION (PROTEASE/METHYLTRANSFERASE P150).
RX PubMed=1518855; DOI=10.1073/pnas.89.17.8259;
RA Koonin E.V., Gorbalenya A.E., Purdy M.A., Rozanov M.N., Reyes G.R.,
RA Bradley D.W.;
RT "Computer-assisted assignment of functional domains in the nonstructural
RT polyprotein of hepatitis E virus: delineation of an additional group of
RT positive-strand RNA plant and animal viruses.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8259-8263(1992).
RN [3]
RP ACTIVE SITE, PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL POLYPROTEIN P200), AND
RP MUTAGENESIS OF HIS-1248; HIS-1273; HIS-1290; GLY-1300; GLY-1301; GLY-1302
RP AND TYR-1316.
RX PubMed=8676497; DOI=10.1128/jvi.70.7.4707-4713.1996;
RA Chen J.P., Strauss J.H., Strauss E.G., Frey T.K.;
RT "Characterization of the rubella virus nonstructural protease domain and
RT its cleavage site.";
RL J. Virol. 70:4707-4713(1996).
RN [4]
RP CATALYTIC ACTIVITY (RNA-DIRECTED RNA POLYMERASE P90), AND FUNCTION
RP (RNA-DIRECTED RNA POLYMERASE P90).
RX PubMed=8599224; DOI=10.1006/viro.1996.0125;
RA Gros C., Wengler G.;
RT "Identification of an RNA-stimulated NTPase in the predicted helicase
RT sequence of the Rubella virus nonstructural polyprotein.";
RL Virology 217:367-372(1996).
RN [5]
RP INTERACTION WITH HUMAN RB1 (RNA-DIRECTED RNA POLYMERASE P90).
RX PubMed=9608663; DOI=10.1023/a:1007998023047;
RA Atreya C.D., Lee N.S., Forng R.Y., Hofmann J., Washington G., Marti G.,
RA Nakhasi H.L.;
RT "The rubella virus putative replicase interacts with the retinoblastoma
RT tumor suppressor protein.";
RL Virus Genes 16:177-183(1998).
RN [6]
RP FUNCTION (PROTEASE/METHYLTRANSFERASE P150), COFACTOR, PROTEOLYTIC CLEAVAGE
RP (NON-STRUCTURAL POLYPROTEIN P200), AND CATALYTIC ACTIVITY
RP (PROTEASE/METHYLTRANSFERASE P150).
RX PubMed=9557742; DOI=10.1128/jvi.72.5.4463-4466.1998;
RA Liu X., Ropp S.L., Jackson R.J., Frey T.K.;
RT "The rubella virus nonstructural protease requires divalent cations for
RT activity and functions in trans.";
RL J. Virol. 72:4463-4466(1998).
RN [7]
RP MUTAGENESIS OF CYS-1904, AND INTERACTION WITH HUMAN RB1 (RNA-DIRECTED RNA
RP POLYMERASE P90).
RX PubMed=10073691; DOI=10.1099/0022-1317-80-2-327;
RA Forng R.Y., Atreya C.D.;
RT "Mutations in the retinoblastoma protein-binding LXCXE motif of rubella
RT virus putative replicase affect virus replication.";
RL J. Gen. Virol. 80:327-332(1999).
RN [8]
RP ZINC-BINDING (PROTEASE/METHYLTRANSFERASE P150), AND MUTAGENESIS OF
RP CYS-1152; CYS-1167; CYS-1175; CYS-1178; HIS-1190; HIS-1204; CYS-1225;
RP CYS-1227; HIS-1236 AND HIS-1273.
RX PubMed=10846076; DOI=10.1128/jvi.74.13.5949-5956.2000;
RA Liu X., Yang J., Ghazi A.M., Frey T.K.;
RT "Characterization of the zinc binding activity of the rubella virus
RT nonstructural protease.";
RL J. Virol. 74:5949-5956(2000).
RN [9]
RP FUNCTION (PROTEASE/METHYLTRANSFERASE P150), DOMAIN
RP (PROTEASE/METHYLTRANSFERASE P150), AND PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL
RP POLYPROTEIN P200).
RX PubMed=10823845; DOI=10.1128/jvi.74.12.5412-5423.2000;
RA Liang Y., Yao J., Gillam S.;
RT "Rubella virus nonstructural protein protease domains involved in
RT trans- and cis-cleavage activities.";
RL J. Virol. 74:5412-5423(2000).
RN [10]
RP MUTAGENESIS OF GLY-1966; ASP-1967 AND ASP-1968, AND CATALYTIC ACTIVITY
RP (RNA-DIRECTED RNA POLYMERASE P90).
RX PubMed=11437666; DOI=10.1006/viro.2001.0939;
RA Wang X., Gillam S.;
RT "Mutations in the GDD motif of rubella virus putative RNA-dependent RNA
RT polymerase affect virus replication.";
RL Virology 285:322-331(2001).
RN [11]
RP FUNCTION (NON-STRUCTURAL POLYPROTEIN P200), PROTEOLYTIC CLEAVAGE
RP (NON-STRUCTURAL POLYPROTEIN P200), FUNCTION (PROTEASE/METHYLTRANSFERASE
RP P150), AND FUNCTION (RNA-DIRECTED RNA POLYMERASE P90).
RX PubMed=11289813; DOI=10.1006/viro.2001.0862;
RA Liang Y., Gillam S.;
RT "Rubella virus RNA replication is cis-preferential and synthesis of
RT negative- and positive-strand RNAs is regulated by the processing of
RT nonstructural protein.";
RL Virology 282:307-319(2001).
RN [12]
RP FUNCTION (NON-STRUCTURAL POLYPROTEIN P200), FUNCTION
RP (PROTEASE/METHYLTRANSFERASE P150), FUNCTION (RNA-DIRECTED RNA POLYMERASE
RP P90), PROTEOLYTIC CLEAVAGE (NON-STRUCTURAL POLYPROTEIN P200), AND CATALYTIC
RP ACTIVITY (PROTEASE/METHYLTRANSFERASE P150).
RX PubMed=12076835; DOI=10.1016/s0168-1702(02)00077-1;
RA Wang X., Liang Y., Gillam S.;
RT "Rescue of rubella virus replication-defective mutants using vaccinia virus
RT recombinant expressing rubella virus nonstructural proteins.";
RL Virus Res. 86:111-122(2002).
RN [13]
RP DOMAIN (PROTEASE/METHYLTRANSFERASE P150), AND MUTAGENESIS OF ASP-1210 AND
RP ASP-1217.
RX PubMed=17475644; DOI=10.1128/jvi.00605-07;
RA Zhou Y., Tzeng W.P., Yang W., Zhou Y., Ye Y., Lee H.W., Frey T.K., Yang J.;
RT "Identification of a Ca2+-binding domain in the rubella virus nonstructural
RT protease.";
RL J. Virol. 81:7517-7528(2007).
RN [14]
RP SUBCELLULAR LOCATION (PROTEASE/METHYLTRANSFERASE P150), DOMAIN
RP (PROTEASE/METHYLTRANSFERASE P150), AND SUBCELLULAR LOCATION (RNA-DIRECTED
RP RNA POLYMERASE P90).
RX PubMed=19539969; DOI=10.1016/j.virol.2009.05.019;
RA Matthews J.D., Tzeng W.P., Frey T.K.;
RT "Determinants of subcellular localization of the rubella virus
RT nonstructural replicase proteins.";
RL Virology 390:315-323(2009).
RN [15]
RP INTERACTION WITH HOST CALM1 (PROTEASE/METHYLTRANSFERASE P150), AND
RP MUTAGENESIS OF ARG-1165.
RX PubMed=20086014; DOI=10.1074/jbc.m109.097063;
RA Zhou Y., Tzeng W.P., Wong H.C., Ye Y., Jiang J., Chen Y., Huang Y.,
RA Suppiah S., Frey T.K., Yang J.J.;
RT "Calcium-dependent association of calmodulin with the rubella virus
RT nonstructural protease domain.";
RL J. Biol. Chem. 285:8855-8868(2010).
RN [16]
RP FUNCTION (PROTEASE/METHYLTRANSFERASE P150), SUBCELLULAR LOCATION
RP (PROTEASE/METHYLTRANSFERASE P150), AND MUTAGENESIS OF GLU-36; ARG-38;
RP ASP-39; THR-42; GLN-45; LYS-46; ARG-47 AND ILE-49.
RX PubMed=20696450; DOI=10.1016/j.virol.2010.07.025;
RA Matthews J.D., Tzeng W.P., Frey T.K.;
RT "Analysis of the function of cytoplasmic fibers formed by the rubella virus
RT nonstructural replicase proteins.";
RL Virology 406:212-227(2010).
RN [17]
RP INTERACTION WITH RNA-DIRECTED RNA POLYMERASE P90
RP (PROTEASE/METHYLTRANSFERASE P150), INTERACTION WITH
RP PROTEASE/METHYLTRANSFERASE P150 (RNA-DIRECTED RNA POLYMERASE P90),
RP MUTAGENESIS OF GLU-36; ARG-38; ASP-39; THR-42; GLN-45; LYS-46; ARG-47 AND
RP ILE-49, AND SUBCELLULAR LOCATION (NON-STRUCTURAL POLYPROTEIN P200).
RX PubMed=22491463; DOI=10.1128/jvi.06132-11;
RA Matthews J.D., Tzeng W.P., Frey T.K.;
RT "Determinants in the maturation of rubella virus p200 replicase polyprotein
RT precursor.";
RL J. Virol. 86:6457-6469(2012).
RN [18]
RP INTERACTION WITH HOST C1QBP (ROTEASE/METHYLTRANSFERASE P150), DOMAIN
RP (ROTEASE/METHYLTRANSFERASE P150), AND MUTAGENESIS OF 727-PRO--PRO-730 AND
RP 747-PRO--PRO-750.
RX PubMed=22238231; DOI=10.1099/vir.0.038901-0;
RA Suppiah S., Mousa H.A., Tzeng W.P., Matthews J.D., Frey T.K.;
RT "Binding of cellular p32 protein to the rubella virus P150 replicase
RT protein via PxxPxR motifs.";
RL J. Gen. Virol. 93:807-816(2012).
RN [19]
RP INTERACTION WITH THE CAPSID PROTEIN (PROTEASE/METHYLTRANSFERASE P150), AND
RP SUBCELLULAR LOCATION (PROTEASE/METHYLTRANSFERASE P150).
RC STRAIN=RVi/Japan/Hiroshima/2003;
RX PubMed=25056903; DOI=10.1128/jvi.01758-14;
RA Sakata M., Otsuki N., Okamoto K., Anraku M., Nagai M., Takeda M., Mori Y.;
RT "Short self-interacting N-terminal region of rubella virus capsid protein
RT is essential for cooperative actions of capsid and nonstructural p150
RT proteins.";
RL J. Virol. 88:11187-11198(2014).
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:0000269|PubMed:11289813, ECO:0000269|PubMed:12076835}.
CC -!- FUNCTION: [Protease/methyltransferase p150]: Protease that cleaves the
CC precursor polyprotein into two mature products (PubMed:10823845,
CC PubMed:9557742). Together with RNA-directed RNA polymerase p90,
CC replicates the 40S genomic and antigenomic RNA by recognizing
CC replications specific signals. The heterodimer P150/p90 is probably the
CC principal replicase for positive-strand genomic RNA and the 24S
CC subgenomic RNA, which codes for structural proteins (PubMed:11289813,
CC PubMed:12076835). Responsible for the mRNA-capping of the viral mRNAs.
CC This function is necessary since all viral RNAs are synthesized in the
CC cytoplasm, and host capping enzymes are restricted to the nucleus
CC (Probable). Forms fibers late in the infection that may be involved in
CC cell-to-cell spread of the virus RNA in the absence of virus particle
CC formation (PubMed:20696450). {ECO:0000269|PubMed:10823845,
CC ECO:0000269|PubMed:11289813, ECO:0000269|PubMed:12076835,
CC ECO:0000269|PubMed:20696450, ECO:0000269|PubMed:9557742,
CC ECO:0000305|PubMed:1518855}.
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 (PubMed:11289813, PubMed:12076835). A helicase
CC activity is probably also present (PubMed:8599224).
CC {ECO:0000269|PubMed:11289813, ECO:0000269|PubMed:12076835,
CC ECO:0000269|PubMed:8599224}.
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:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:11437666};
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:0000269|PubMed:8599224};
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 -!- 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, ECO:0000269|PubMed:9557742};
CC -!- SUBUNIT: [Protease/methyltransferase p150]: Interacts with RNA-directed
CC RNA polymerase p90 (PubMed:22491463). Interacts with host CALM1; this
CC interaction is necessary for the protease activity and viral
CC infectivity (PubMed:20086014). Interacts with host C1QBP
CC (PubMed:22238231). Interacts with the capsid protein (PubMed:25056903).
CC {ECO:0000269|PubMed:20086014, ECO:0000269|PubMed:22238231,
CC ECO:0000269|PubMed:22491463, ECO:0000269|PubMed:25056903}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase p90]: Interacts with human
CC RB1/retinoblastoma protein (PubMed:10073691, 9608663). Interacts with
CC protease/methyltransferase p150 (PubMed:22491463).
CC {ECO:0000269|PubMed:10073691, ECO:0000269|PubMed:22491463,
CC ECO:0000269|PubMed:9608663}.
CC -!- INTERACTION:
CC PRO_0000041224; Q96BM9: ARL8A; Xeno; NbExp=2; IntAct=EBI-11478518, EBI-4401082;
CC PRO_0000041225; P06400: RB1; Xeno; NbExp=3; IntAct=EBI-2568719, EBI-491274;
CC -!- SUBCELLULAR LOCATION: [Non-structural polyprotein p200]: Host membrane
CC {ECO:0000269|PubMed:19539969}. Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:22491463}. Host cytoplasm
CC {ECO:0000269|PubMed:19539969}. Note=Localizes to cytoplasmic foci at 24
CC hpi. {ECO:0000269|PubMed:19539969}.
CC -!- SUBCELLULAR LOCATION: [Protease/methyltransferase p150]: Host membrane
CC {ECO:0000269|PubMed:19539969, ECO:0000269|PubMed:25056903}. Host
CC cytoplasm, host perinuclear region {ECO:0000269|PubMed:20696450,
CC ECO:0000269|PubMed:22491463}. Host cytoplasm
CC {ECO:0000269|PubMed:19539969, ECO:0000269|PubMed:25056903}. Note=At 36
CC hpi, localizes to the host cytoplasm, probably in vesicles inside host
CC vacuoles of endosomal and lysosomal origin (By similarity). At 72 hpi,
CC localizes to filamentous structures in the host cytoplasm
CC (PubMed:25056903). {ECO:0000250|UniProtKB:P13889,
CC ECO:0000269|PubMed:25056903}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase p90]: Host membrane
CC {ECO:0000269|PubMed:19539969}. Host cytoplasm
CC {ECO:0000269|PubMed:19539969}. Note=Localizes to the cytoplasm and to
CC the cytoplasmic fibers formed by protease/methyltransferase p150.
CC {ECO:0000269|PubMed:19539969}.
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 (PubMed:10823845). Both the N-terminus
CC and C-terminus are required for fiber formation. The N-terminus is
CC involved in associating with membranes (PubMed:19539969). An EF-hand
CC Ca(2+)-binding motif is present in the protease (PubMed:17475644). Also
CC contains 3 SH3-binding motifs that are responsible for the interaction
CC with host C1QBP (PubMed:22238231). {ECO:0000269|PubMed:10823845,
CC ECO:0000269|PubMed:17475644, ECO:0000269|PubMed:19539969,
CC ECO:0000269|PubMed:22238231}.
CC -!- PTM: [Non-structural polyprotein p200]: Specific enzymatic cleavage by
CC its own cysteine protease yield mature proteins p150 and p90.
CC {ECO:0000269|PubMed:10823845, ECO:0000269|PubMed:11289813,
CC ECO:0000269|PubMed:12076835, ECO:0000269|PubMed:8676497,
CC ECO:0000269|PubMed:9557742, ECO:0000269|PubMed:9656995}.
CC -!- MISCELLANEOUS: Rubella virus in utero infection has frequently severe
CC consequences on normal fetal development, collectively known as
CC congenital rubella syndrome (CRS) (Probable). The teratogenicity of the
CC virus is possibly due to the interaction between the p90 protein and
CC the human RB1/retinoblastoma protein (PubMed:9608663).
CC {ECO:0000303|PubMed:9608663, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA51087.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X72393; CAA51087.1; ALT_SEQ; Genomic_RNA.
DR PIR; S38480; S38480.
DR SMR; Q86500; -.
DR IntAct; Q86500; 22.
DR MEROPS; C27.001; -.
DR PRIDE; Q86500; -.
DR Proteomes; UP000007143; 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; Reference proteome; RNA-directed RNA polymerase; Thiol protease;
KW Transferase; Viral RNA replication; Zinc.
FT CHAIN 1..2116
FT /note="Non-structural polyprotein p200"
FT /id="PRO_0000249224"
FT CHAIN 1..1301
FT /note="Protease/methyltransferase p150"
FT /id="PRO_0000041224"
FT CHAIN 1302..2116
FT /note="RNA-directed RNA polymerase p90"
FT /id="PRO_0000041225"
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 REGION 715..779
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 ECO:0000269|PubMed:20086014"
FT REGION 1193..1228
FT /note="EF-hand-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:17475644"
FT REGION 1700..1900
FT /note="Involved in P150-P90 interaction"
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MOTIF 727..732
FT /note="PxxPxR; class II SH3-binding"
FT /evidence="ECO:0000269|PubMed:22238231"
FT MOTIF 747..752
FT /note="PxxPxR; class II SH3-binding"
FT /evidence="ECO:0000269|PubMed:22238231"
FT MOTIF 761..766
FT /note="PxxPxR; class II SH3-binding"
FT /evidence="ECO:0000269|PubMed:22238231"
FT MOTIF 1902..1906
FT /note="Human RB1 binding"
FT /evidence="ECO:0000269|PubMed:10073691"
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 ECO:0000269|PubMed:9656995"
FT ACT_SITE 1273
FT /note="For cysteine protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:8676497"
FT BINDING 1175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:10846076"
FT BINDING 1178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:10846076"
FT BINDING 1227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:10846076"
FT BINDING 1273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01237,
FT ECO:0000269|PubMed:10846076"
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,
FT ECO:0000269|PubMed:8676497, ECO:0000269|PubMed:9656995"
FT MUTAGEN 36
FT /note="E->A: Loss of P150-P90 interaction. No effect on
FT processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 38
FT /note="R->A: No effect on P150-P90 interaction. No effect
FT on processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 39
FT /note="D->A: No effect on P150-P90 interaction. No effect
FT on processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 42
FT /note="T->A: Slight loss of P150-P90 interaction. No effect
FT on processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 45
FT /note="Q->A: Slight loss of P150-P90 interaction. No effect
FT on processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 46
FT /note="K->A: No effect on P150-P90 interaction. Inhibits
FT fiber formation by p150."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 47
FT /note="R->A: No effect on P150-P90 interaction. No effect
FT on processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 49
FT /note="I->A: Loss of P150-P90 interaction. No effect on
FT processing efficiency or fiber formation."
FT /evidence="ECO:0000269|PubMed:20696450,
FT ECO:0000269|PubMed:22491463"
FT MUTAGEN 727..730
FT /note="PPPP->APPA: Complete loss of interaction with host
FT C1QBP; when associated with Ala-747 and Ala-749."
FT /evidence="ECO:0000269|PubMed:22238231"
FT MUTAGEN 747..750
FT /note="PPAP->APAA: Complete loss of interaction with host
FT C1QBP; when associated with Ala-727 and Ala-729."
FT /evidence="ECO:0000269|PubMed:22238231"
FT MUTAGEN 1152
FT /note="C->S: Complete loss of protease activity."
FT /evidence="ECO:0000269|PubMed:9656995"
FT MUTAGEN 1152
FT /note="C->S: No effect on Zn(2+) binding; complete loss of
FT protease activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1165
FT /note="R->D: Complete loss of interaction of p150 with host
FT CALM1."
FT /evidence="ECO:0000269|PubMed:20086014"
FT MUTAGEN 1165
FT /note="R->Q: Decreased interaction of p150 with host
FT CALM1."
FT /evidence="ECO:0000269|PubMed:20086014"
FT MUTAGEN 1167
FT /note="C->S: No effect on Zn(2+) binding; complete loss of
FT protease activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1175
FT /note="C->S: Complete loss of Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1178
FT /note="C->S: Complete loss of Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1190
FT /note="H->L: No effect on Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1204
FT /note="H->L: No effect on Zn(2+) binding; complete loss of
FT protease activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1210
FT /note="D->A: 20 fold decreased infectivity. Loss of Ca(2+)
FT binding."
FT /evidence="ECO:0000269|PubMed:17475644"
FT MUTAGEN 1217
FT /note="D->A: 20 fold decreased infectivity. Loss of Ca(2+)
FT binding."
FT /evidence="ECO:0000269|PubMed:17475644"
FT MUTAGEN 1225
FT /note="C->S: No effect on Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1227
FT /note="C->S: Complete loss of Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1236
FT /note="H->S: No effect on protease activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1248
FT /note="H->L: No effect on protease activity."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1273
FT /note="H->L: Complete loss of protease activity."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1273
FT /note="H->S: Complete loss of Zn(2+) binding and protease
FT activity."
FT /evidence="ECO:0000269|PubMed:10846076"
FT MUTAGEN 1290
FT /note="H->L: No effect on protease activity."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1300
FT /note="G->A: Partial loss of proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1300
FT /note="G->S: Complete loss of polyprotein cleavage."
FT /evidence="ECO:0000269|PubMed:9656995"
FT MUTAGEN 1300
FT /note="G->V: Complete loss of proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1301
FT /note="G->A: Almost complete loss of proteolytic cleavage
FT of non-structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1301
FT /note="G->V: Complete loss of proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1302
FT /note="G->A: Partial loss of proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1302
FT /note="G->V: Complete loss of proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1316
FT /note="Y->M: No effect on proteolytic cleavage of non-
FT structural polyprotein p200."
FT /evidence="ECO:0000269|PubMed:8676497"
FT MUTAGEN 1904
FT /note="C->G: Partial loss of human RB1 binding and 47% loss
FT of virus replication."
FT /evidence="ECO:0000269|PubMed:10073691"
FT MUTAGEN 1904
FT /note="C->R: Complete loss of human RB1 binding and virus
FT replication."
FT /evidence="ECO:0000269|PubMed:10073691"
FT MUTAGEN 1966
FT /note="G->A: Reduces virus infectivity."
FT /evidence="ECO:0000269|PubMed:11437666"
FT MUTAGEN 1967
FT /note="D->A: Complete loss of virus replication."
FT /evidence="ECO:0000269|PubMed:11437666"
FT MUTAGEN 1968
FT /note="D->A: Complete loss of virus replication."
FT /evidence="ECO:0000269|PubMed:11437666"
SQ SEQUENCE 2116 AA; 230910 MW; 04DD4C97B704EC8E CRC64;
MEKLLDEVLA PGGPYNLTVG SWVRDHVRSI VEGAWEVRDV VTAAQKRAIV 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 VGWWRWFSLP RPVFQRMLSY CKTLSPDAYY SERVFKFKNA
LSHSITLAGN VLQEGWKGTC AEEDALCAYV AFRAWQSNAR LAGIMKSAKR CAADSLSVAG
WLDTIWDAIK RFFGSVPLAE RMEEWEQDAA VAAFDRGPLE DGGRHLDTVQ PPKSPPRPEI
AATWIVHAAS ADRHCACAPR CDVPRERPSA PAGPPDDEAL IPPWLFAERR ALRCREWDFE
ALRARADTAA APAPLAPRPA RYPTVLYRHP AHHGPWLTLD EPGGADAALV LCDPLGQPLR
GPERHYAAGA HMCAQARGLQ AFVRVVPPPE RPWADGGARA WAKFFRGCAW AQRLLGEPAV
MHLPYTDGDV PKLIALALRT LAQQGAALAL SVRDLPRGTA FEANAVTAAV RAGPGQLAAT
SPPPGDPPPP RRARRSQRHS DARGTPPPAP VRDPPRPQPS PPAPPRVGDP VPPTTAEPAD
RARHAELEVV YEPSGPPTST KADPDSDIVE SYARAAGPVH LRVRDIMDPP PGCKVVVNAA
NEGLLAGSGV CGAIFANATA ALAADCRRLA PCPIGEAVAT PGHGCGYTHI IHAVAPRRPR
DPAALEEGEA LLERAYRSIV ALAAARRWAR VACPLLGAGV YGWSAAESLR AALAATRAEP
AERVSLHICH PDRATLTHAS VLVGAGLAAR RVSPPPTEPL ASCPAGDPGR PAQRSASPPA
TPLGDATAPE PRGCQGCELC RYTRVTNDRA YVNLWLERDR GATSWAMRIP EVVVYGPEHL
ATHFPLNHYS VLKPAEVRPP RGMCGSDMWR CRGWQGMPQV RCTPSNAHAA LCRTGVPPRV
STRGGELDPN TCWLRAAANV AQAARACGAY TSAGCPKCAY GRALSEARTH EDFAALSQWW
SASHADASPD GTGDPLDPLM ETVGCACSRV WVGSEHEAPP DHLLVSLHRA PNGPWGVVLE
VRARPEGGNP TGHFVCAVGG GPRRVSDRPH LWLAVPLSRG GGTCAATDEG LAQAYYDDLE
VRRLGDDAMA RAALASIQRP RKGPYNIRVW NMAAGAGKTT RILAAFTRED LYVCPTNALL
HEIQAKLRAR DIDIKNAATY ERALTKPLAA YRRIYIDEAF TLGGEYCAFV ASQTTAEVIC
VGDRDQCGPH YANNCRTPVP DRWPTGRSRH TWRFPDCWAA RLRAGLDYDI EGERTGTFAC
NLWDGRQVDL HLAFSRETVR RLHEAGIRAY TVREAQGMSV GTACIHVGRD GTDVALALTR
DLAIVSLTRA SDALYLHELE DGLLRAAGLS AFLDAGALAE LKEVPAGIDR VVAVEQAPPP
LPPADGIPEA QDVPPFCPRT LEELVFGRAG HPHYADLNRV TEGEREVRYM RISRHLLNKN
HTEMPGTERV LSAVCAVRRY RAGEDGSTLR TAVARQHPRP FRQIPPPRVT AGVAQEWRMT
YLRERIDLTD VYTQMGVAAR ELTDRYTRRY PEIFAGMCTA QSLSVPAFLK ATLKCVDAAL
GPRDTEDCHA AQGKAGLEIR AWAKEWVQVM SPHFRAIQKI IMRALRPQFL VAAGHTEPEV
DAWWQAHYTT NAIEVDFTEF DMNQTLATRD VELEISAALL GLPCAEDYRA LRAGSYCTLR
ELGSTETGCE RTSGEPATLL HNTTVAMCMA MRMVPKGVRW AGIFQGDDMV IFLPEGARNA
ALKWTPAEVG LFGFHIPVKH VSTPTPSFCG HVGTAAGLFH DVMHQAIKVL CRRFDPDVLE
EQQVALLDRL RGVYAALPDT VAANAAYYDY SAERVLAIVR ELTAYARGRG LDHPATIGAL
EEIQTPYARA NLHDAD
