Lipid Modification Database
Tag Content
LipidDB ID
LipidDB-11034-00947
Entry Name
UniProt Accession
Theoretical PI
8.3
Molecular Weight
279549.22
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
RNA-directed RNA polymerase nsP4
Protein Synonyms/Alias
Polyprotein nsP1234; P1234; 2.1.1.-; 2.7.7.-; Non-structural protein 1; 3.1.3.33; 3.4.22.-; 3.6.1.15; 3.6.4.13; Non-structural protein 2; nsP2; nsP3; nsP3'; 2.7.7.48; Non-structural protein 4; nsP4;
Gene Name
Gene Synonyms/Alias
Created Date
21-JUL-1986
 Lipid Modification Sites 
 Position   Sequence Form   Peptide   References   Modification Type 
420
Canonical
ERKLTYGCLWAFRTK
[1]
S-Palmitoylation
Organism
Sindbis virus (SINV)
NCBI Taxa ID
11034
Reference
[1] Ahola T, Kujala P, Tuittila M, Blom T, Laakkonen P, Hinkkanen A, Auvinen P.Effects of palmitoylation of replicase protein nsP1 on alphavirus infection. JVirol. 2000 Aug;74(15):6725-33.[PMID:10888610]
Functional Description
P123 and P123' are short-lived polyproteins, accumulating during early stage of infection. P123 is directly translated from the genome, whereas P123' is a product of the cleavage of P1234. They localize the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, they start viral genome replication into antigenome. After these early events, P123 and P123' are cleaved sequentially into nsP1, nsP2 and nsP3/nsP3'. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex.nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response.nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins. nsP4 is a short-lived protein regulated by several ways: the opal codon readthrough and degradation by ubiquitin pathway.
Sequence Annotation
Domain: 695 850 (+)RNA virus helicase ATP-binding.
Domain: 851 999 (+)RNA virus helicase C-terminal.
Domain: 1012 1341 Peptidase C9.
Domain: 1348 1507 Macro.
Domain: 2266 2381 RdRp catalytic.
Nucleotide-binding: 726 733 ATP.
Region: 245 264 nsP1 membrane-binding.
Region: 1013 1032 Nucleolus localization signal.
Motif: 1196 1200 Nuclear localization signal.
Active site: 1021 1021 For cysteine protease nsP2 activity.
Active site: 1098 1098 For cysteine protease nsP2 activity.
Functional site: 540 541 Cleavage; by nsP2.
Functional site: 1347 1348 Cleavage; by nsP2.
Functional site: 1902 1903 Cleavage; by nsP2.
Protein Length
2512 AA.
Protein Sequence
(Canonical)
MEKPVVNVDV DPQSPFVVQL QKSFPQFEVV AQQVTPNDHA NARAFSHLAS KLIELEVPTT  60
ATILDIGSAP ARRMFSEHQY HCVCPMRSPE DPDRMMKYAS KLAEKACKIT NKNLHEKIKD  120
LRTVLDTPDA ETPSLCFHND VTCNMRAEYS VMQDVYINAP GTIYHQAMKG VRTLYWIGFD  180
TTQFMFSAMA GSYPAYNTNW ADEKVLEARN IGLCSTKLSE GRTGKLSIMR KKELKPGSRV  240
YFSVGSTLYP EHRASLQSWH LPSVFHLNGK QSYTCRCDTV VSCEGYVVKK ITISPGITGE  300
TVGYAVTHNS EGFLLCKVTD TVKGERVSFP VCTYIPATIC DQMTGIMATD ISPDDAQKLL  360
VGLNQRIVIN GRTNRNTNTM QNYLLPIIAQ GFSKWAKERK DDLDNEKMLG TRERKLTYGC  420
LWAFRTKKVH SFYRPPGTQT CVKVPASFSA FPMSSVWTTS LPMSLRQKLK LALQPKKEEK  480
LLQVSEELVM EAKAAFEDAQ EEARAEKLRE ALPPLVADKG IEAAAEVVCE VEGLQADIGA  540
ALVETPRGHV RIIPQANDRM IGQYIVVSPN SVLKNAKLAP AHPLADQVKI ITHSGRSGRY  600
AVEPYDAKVL MPAGGAVPWP EFLALSESAT LVYNEREFVN RKLYHIAMHG PAKNTEEEQY  660
KVTKAELAET EYVFDVDKKR CVKKEEASGL VLSGELTNPP YHELALEGLK TRPAVPYKVE  720
TIGVIGTPGS GKSAIIKSTV TARDLVTSGK KENCREIEAD VLRLRGMQIT SKTVDSVMLN  780
GCHKAVEVLY VDEAFACHAG ALLALIAIVR PRKKVVLCGD PMQCGFFNMM QLKVHFNHPE  840
KDICTKTFYK YISRRCTQPV TAIVSTLHYD GKMKTTNPCK KNIEIDITGA TKPKPGDIIL  900
TCFRGWVKQL QIDYPGHEVM TAAASQGLTR KGVYAVRQKV NENPLYAITS EHVNVLLTRT  960
EDRLVWKTLQ GDPWIKQPTN IPKGNFQATI EDWEAEHKGI IAAINSPTPR ANPFSCKTNV  1020
CWAKALEPIL ATAGIVLTGC QWSELFPQFA DDKPHSAIYA LDVICIKFFG MDLTSGLFSK  1080
QSIPLTYHPA DSARPVAHWD NSPGTRKYGY DHAIAAELSR RFPVFQLAGK GTQLDLQTGR  1140
TRVISAQHNL VPVNRNLPHA LVPEYKEKQP GPVKKFLNQF KHHSVLVVSE EKIEAPRKRI  1200
EWIAPIGIAG ADKNYNLAFG FPPQARYDLV FINIGTKYRN HHFQQCEDHA ATLKTLSRSA  1260
LNCLNPGGTL VVKSYGYADR NSEDVVTALA RKFVRVSAAR PDCVSSNTEM YLIFRQLDNS  1320
RTRQFTPHHL NCVISSVYEG TRDGVGAAPS YRTKRENIAD CQEEAVVNAA NPLGRPGEGV  1380
CRAIYKRWPT SFTDSATETG TARMTVCLGK KVIHAVGPDF RKHPEAEALK LLQNAYHAVA  1440
DLVNEHNIKS VAIPLLSTGI YAAGKDRLEV SLNCLTTALD RTDADVTIYC LDKKWKERID  1500
AALQLKESVT ELKDEDMEID DELVWIHPDS CLKGRKGFST TKGKLYSYFE GTKFHQAAKD  1560
MAEIKVLFPN DQESNEQLCA YILGETMEAI REKCPVDHNP SSSPPKTLPC LCMYAMTPER  1620
VHRLRSNNVK EVTVCSSTPL PKHKIKNVQK VQCTKVVLFN PHTPAFVPAR KYIEVPEQPT  1680
APPAQAEEAP EVVATPSPST ADNTSLDVTD ISLDMDDSSE GSLFSSFSGS DNSITSMDSW  1740
SSGPSSLEIV DRRQVVVADV HAVQEPAPIP PPRLKKMARL AAARKEPTPP ASNSSESLHL  1800
SFGGVSMSLG SIFDGETARQ AAVQPLATGP TDVPMSFGSF SDGEIDELSR RVTESEPVLF  1860
GSFEPGEVNS IISSRSAVSF PLRKQRRRRR SRRTEYLTGV GGYIFSTDTG PGHLQKKSVL  1920
QNQLTEPTLE RNVLERIHAP VLDTSKEEQL KLRYQMMPTE ANKSRYQSRK VENQKAITTE  1980
RLLSGLRLYN SATDQPECYK ITYPKPLYSS SVPANYSDPQ FAVAVCNNYL HENYPTVASY  2040
QITDEYDAYL DMVDGTVACL DTATFCPAKL RSYPKKHEYR APNIRSAVPS AMQNTLQNVL  2100
IAATKRNCNV TQMRELPTLD SATFNVECFR KYACNDEYWE EFARKPIRIT TEFVTAYVAR  2160
LKGPKAAALF AKTYNLVPLQ EVPMDRFVMD MKRDVKVTPG TKHTEERPKV QVIQAAEPLA  2220
TAYLCGIHRE LVRRLTAVLL PNIHTLFDMS AEDFDAIIAE HFKQGDPVLE TDIASFDKSQ  2280
DDAMALTGLM ILEDLGVDQP LLDLIECAFG EISSTHLPTG TRFKFGAMMK SGMFLTLFVN  2340
TVLNVVIASR VLEERLKTSR CAAFIGDDNI IHGVVSDKEM AERCATWLNM EVKIIDAVIG  2400
ERPPYFCGGF ILQDSVTSTA CRVADPLKRL FKLGKPLPAD DEQDEDRRRA LLDETKAWFR  2460
VGITGTLAVA VTTRYEVDNI TPVLLALRTF AQSKRAFQAI RGEIKHLYGG PK          2512
FASTA
(Canonical)
>LipidDB-11034-00947|P03317
MEKPVVNVDVDPQSPFVVQLQKSFPQFEVVAQQVTPNDHANARAFSHLASKLIELEVPTT
ATILDIGSAPARRMFSEHQYHCVCPMRSPEDPDRMMKYASKLAEKACKITNKNLHEKIKD
LRTVLDTPDAETPSLCFHNDVTCNMRAEYSVMQDVYINAPGTIYHQAMKGVRTLYWIGFD
TTQFMFSAMAGSYPAYNTNWADEKVLEARNIGLCSTKLSEGRTGKLSIMRKKELKPGSRV
YFSVGSTLYPEHRASLQSWHLPSVFHLNGKQSYTCRCDTVVSCEGYVVKKITISPGITGE
TVGYAVTHNSEGFLLCKVTDTVKGERVSFPVCTYIPATICDQMTGIMATDISPDDAQKLL
VGLNQRIVINGRTNRNTNTMQNYLLPIIAQGFSKWAKERKDDLDNEKMLGTRERKLTYGC
LWAFRTKKVHSFYRPPGTQTCVKVPASFSAFPMSSVWTTSLPMSLRQKLKLALQPKKEEK
LLQVSEELVMEAKAAFEDAQEEARAEKLREALPPLVADKGIEAAAEVVCEVEGLQADIGA
ALVETPRGHVRIIPQANDRMIGQYIVVSPNSVLKNAKLAPAHPLADQVKIITHSGRSGRY
AVEPYDAKVLMPAGGAVPWPEFLALSESATLVYNEREFVNRKLYHIAMHGPAKNTEEEQY
KVTKAELAETEYVFDVDKKRCVKKEEASGLVLSGELTNPPYHELALEGLKTRPAVPYKVE
TIGVIGTPGSGKSAIIKSTVTARDLVTSGKKENCREIEADVLRLRGMQITSKTVDSVMLN
GCHKAVEVLYVDEAFACHAGALLALIAIVRPRKKVVLCGDPMQCGFFNMMQLKVHFNHPE
KDICTKTFYKYISRRCTQPVTAIVSTLHYDGKMKTTNPCKKNIEIDITGATKPKPGDIIL
TCFRGWVKQLQIDYPGHEVMTAAASQGLTRKGVYAVRQKVNENPLYAITSEHVNVLLTRT
EDRLVWKTLQGDPWIKQPTNIPKGNFQATIEDWEAEHKGIIAAINSPTPRANPFSCKTNV
CWAKALEPILATAGIVLTGCQWSELFPQFADDKPHSAIYALDVICIKFFGMDLTSGLFSK
QSIPLTYHPADSARPVAHWDNSPGTRKYGYDHAIAAELSRRFPVFQLAGKGTQLDLQTGR
TRVISAQHNLVPVNRNLPHALVPEYKEKQPGPVKKFLNQFKHHSVLVVSEEKIEAPRKRI
EWIAPIGIAGADKNYNLAFGFPPQARYDLVFINIGTKYRNHHFQQCEDHAATLKTLSRSA
LNCLNPGGTLVVKSYGYADRNSEDVVTALARKFVRVSAARPDCVSSNTEMYLIFRQLDNS
RTRQFTPHHLNCVISSVYEGTRDGVGAAPSYRTKRENIADCQEEAVVNAANPLGRPGEGV
CRAIYKRWPTSFTDSATETGTARMTVCLGKKVIHAVGPDFRKHPEAEALKLLQNAYHAVA
DLVNEHNIKSVAIPLLSTGIYAAGKDRLEVSLNCLTTALDRTDADVTIYCLDKKWKERID
AALQLKESVTELKDEDMEIDDELVWIHPDSCLKGRKGFSTTKGKLYSYFEGTKFHQAAKD
MAEIKVLFPNDQESNEQLCAYILGETMEAIREKCPVDHNPSSSPPKTLPCLCMYAMTPER
VHRLRSNNVKEVTVCSSTPLPKHKIKNVQKVQCTKVVLFNPHTPAFVPARKYIEVPEQPT
APPAQAEEAPEVVATPSPSTADNTSLDVTDISLDMDDSSEGSLFSSFSGSDNSITSMDSW
SSGPSSLEIVDRRQVVVADVHAVQEPAPIPPPRLKKMARLAAARKEPTPPASNSSESLHL
SFGGVSMSLGSIFDGETARQAAVQPLATGPTDVPMSFGSFSDGEIDELSRRVTESEPVLF
GSFEPGEVNSIISSRSAVSFPLRKQRRRRRSRRTEYLTGVGGYIFSTDTGPGHLQKKSVL
QNQLTEPTLERNVLERIHAPVLDTSKEEQLKLRYQMMPTEANKSRYQSRKVENQKAITTE
RLLSGLRLYNSATDQPECYKITYPKPLYSSSVPANYSDPQFAVAVCNNYLHENYPTVASY
QITDEYDAYLDMVDGTVACLDTATFCPAKLRSYPKKHEYRAPNIRSAVPSAMQNTLQNVL
IAATKRNCNVTQMRELPTLDSATFNVECFRKYACNDEYWEEFARKPIRITTEFVTAYVAR
LKGPKAAALFAKTYNLVPLQEVPMDRFVMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLA
TAYLCGIHRELVRRLTAVLLPNIHTLFDMSAEDFDAIIAEHFKQGDPVLETDIASFDKSQ
DDAMALTGLMILEDLGVDQPLLDLIECAFGEISSTHLPTGTRFKFGAMMKSGMFLTLFVN
TVLNVVIASRVLEERLKTSRCAAFIGDDNIIHGVVSDKEMAERCATWLNMEVKIIDAVIG
ERPPYFCGGFILQDSVTSTACRVADPLKRLFKLGKPLPADDEQDEDRRRALLDETKAWFR
VGITGTLAVAVTTRYEVDNITPVLLALRTFAQSKRAFQAIRGEIKHLYGGPK
Gene Ontology
GO:0044174; C:host cell endosome; IEA:UniProtKB-KW
GO:0044187; C:host cell lysosome; IEA:UniProtKB-KW
GO:0042025; C:host cell nucleus; IEA:UniProtKB-KW
GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-KW
GO:0044157; C:host cell projection; IEA:UniProtKB-KW
GO:0016020; C:membrane; IEA:UniProtKB-KW
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW
GO:0005525; F:GTP binding; IEA:UniProtKB-KW
GO:0004386; F:helicase activity; IEA:UniProtKB-KW
GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro
GO:0004651; F:polynucleotide 5'-phosphatase activity; IEA:UniProtKB-EC
GO:0003723; F:RNA binding; IEA:UniProtKB-KW
GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW
GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW
GO:0039523; P:suppression by virus of host RNA polymerase II activity; IEA:UniProtKB-KW
GO:0006351; P:transcription, DNA-templated; IEA:InterPro
GO:0039694; P:viral RNA genome replication; IEA:InterPro
Interpro
InterPro; IPR027351; (+)RNA_virus_helicase_core_dom
InterPro; IPR002620; Alphavirus_nsp2pro
InterPro; IPR002589; Macro_dom
InterPro; IPR027417; P-loop_NTPase
InterPro; IPR007094; RNA-dir_pol_PSvirus
InterPro; IPR029063; SAM-dependent_MTases-like
InterPro; IPR002588; Tymovirus_MeTrfase
InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol
Pfam
Pfam; PF01661; Macro;
Pfam; PF01707; Peptidase_C9;
Pfam; PF00978; RdRP_2;
Pfam; PF01443; Viral_helicase1;
Pfam; PF01660; Vmethyltransf;
SMART
SMART; SM00506; A1pp;
PROSITE
PROSITE; PS51154; MACRO;
PROSITE; PS51520; NSP2PRO;
PROSITE; PS51657; PSRV_HELICASE;
PROSITE; PS50507; RDRP_SSRNA_POS;
PRINTS