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Protein

Non-structural polyprotein

Gene
N/A
Organism
Sindbis virus (SINV)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.
nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell.
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.
nsP3 and nsP3' are essential for minus strand and subgenomic 26S mRNA synthesis.
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.

Catalytic activityi

S-adenosyl-L-methionine + GTP = m7GTP.
m7GTP + (5')pp-Pur-mRNA = diphosphate + m7G(5')ppp-Pur-mRNA.
(5')ppp-mRNA + H2O = (5')pp-mRNA + phosphate.
A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1021 – 10211For cysteine protease nsP2 activity
Active sitei1098 – 10981For cysteine protease nsP2 activity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi726 – 7338ATPSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase, Methyltransferase, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Eukaryotic host transcription shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Inhibition of host RNA polymerase II by virus, mRNA capping, mRNA processing, Viral RNA replication

Keywords - Ligandi

ATP-binding, GTP-binding, Nucleotide-binding, RNA-binding, S-adenosyl-L-methionine

Protein family/group databases

MEROPSiC09.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural polyprotein
Alternative name(s):
Polyprotein nsP1234
Short name:
P1234
Cleaved into the following 7 chains:
Alternative name(s):
Non-structural protein 1
Alternative name(s):
Non-structural protein 2
Short name:
nsP2
Non-structural protein 3
Short name:
nsP3
Non-structural protein 3'
Short name:
nsP3'
Alternative name(s):
Non-structural protein 4
Short name:
nsP4
OrganismiSindbis virus (SINV)
Taxonomic identifieri11034 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirusWEEV complex
Virus hostiAcrocephalus scirpaceus (Eurasian reed-warbler) [TaxID: 48156]
Aedes [TaxID: 7158]
Culex [TaxID: 53527]
Homo sapiens (Human) [TaxID: 9606]
Motacilla alba (White wagtail) (Pied wagtail) [TaxID: 45807]
Streptopelia turtur [TaxID: 177155]
Proteomesi
  • UP000006710 Componenti: Genome

Subcellular locationi

Non-structural polyprotein :
mRNA-capping enzyme nsP1 :
Protease nsP2 :
Non-structural protein 3 :
Non-structural protein 3' :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host cell projection, Host cytoplasm, Host endosome, Host lysosome, Host membrane, Host nucleus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391H → A: Complete loss of methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi81 – 811H → A: Complete loss of methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi91 – 911D → A: Complete loss of methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi94 – 941R → A: Complete loss of methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi249 – 2491Y → A: Complete loss of methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi369 – 3691I → V: No effect on methyl transferase activity or viral infectivity. 1 Publication
Mutagenesisi420 – 4201C → A: Complete loss of palmitoylation. 1 Publication
Mutagenesisi1021 – 10211C → A: Complete loss of nsP2 protease activity. 1 Publication
Mutagenesisi1098 – 10981H → A: Complete loss of nsP2 protease activity. 1 Publication
Mutagenesisi1099 – 10991W → A: Complete loss of nsP2 protease activity. 1 Publication
Mutagenesisi1896 – 18961Y → YR, YS or YW: Reduces RNA synthesis in early phase of infection. 1 Publication
Mutagenesisi1903 – 19031Y → A: No effect on nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → C: Destabilizes nsP4. 1 Publication
Mutagenesisi1903 – 19031Y → E: Reduces nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → F: Destabilizes nsP4. 1 Publication
Mutagenesisi1903 – 19031Y → L: Reduces nsP4 cleavage and destabilizes nsP4. 1 Publication
Mutagenesisi1903 – 19031Y → M: Reduces nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → N: Reduces nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → P: Complete loss of nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → Q: Reduces nsP4 cleavage. 1 Publication
Mutagenesisi1903 – 19031Y → R: Destabilizes nsP4. 1 Publication
Mutagenesisi1903 – 19031Y → T: Reduces nsP4 cleavage. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 25122512Non-structural polyproteinPRO_0000308405Add
BLAST
Chaini1 – 19021902P123'PRO_0000227771Add
BLAST
Chaini1 – 18961896P123PRO_0000227772Add
BLAST
Chaini1 – 540540mRNA-capping enzyme nsP1PRO_0000041236Add
BLAST
Chaini541 – 1347807Protease nsP2PRO_0000041237Add
BLAST
Chaini1348 – 1902555Non-structural protein 3'PRO_0000041238Add
BLAST
Chaini1348 – 1896549Non-structural protein 3PRO_0000227773Add
BLAST
Chaini1903 – 2512610RNA-directed RNA polymerase nsP4PRO_0000041239Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi420 – 4201S-palmitoyl cysteine; by host1 Publication

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins. The polyprotein is synthesized as P123, or P1234 by stop codon readthrough. These polyproteins are processed differently depending on the stage of infection. In early stages, P1234 is first cleaved in trans, through its nsP2 protease activity, releasing P123' and nsP4. P123/P123' and nsP4 start to replicate the viral genome into its antigenome. After these early events, nsP1 is cleaved in cis by nsP2 protease, releasing the P23/P23' polyprotein. Cleavage of nsP1 exposes an 'activator' at the N-terminus of P23/P23' which induces its cleavage into nsP2 and nsP3 by the viral protease. This sequence of delayed processing would allow correct assembly and membrane association of the RNA-polymerase complex. In the late stage of infection, the presence of free nsP2 in the cytoplasm cleaves P1234 quickly into P12 and P34, then into the four nsP.2 Publications
nsP1 is palmitoylated by host.1 Publication
nsP4 is ubiquitinated; targets the protein for rapid degradation via the ubiquitin system.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei540 – 5412Cleavage; by nsP2
Sitei1347 – 13482Cleavage; by nsP2
Sitei1902 – 19032Cleavage; by nsP2

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

PTM databases

SwissPalmiP03317.

Miscellaneous databases

PMAP-CutDBP03317.

Expressioni

Inductioni

Viral replication produces dsRNA in the late phase of infection, resulting in a strong activation of host EIF2AK2/PKR, leading to almost complete phosphorylation of EIF2A. This inactivates completely cellular translation initiation, resulting in a dramatic shutoff of proteins synthesis. Translation of viral non-structural polyprotein and all cellular proteins are stopped in infected cell between 2 and 4 hours post infection. Only the 26S mRNA is still translated into viral structural proteins, presumably through a unique mechanism of enhancer element which counteract the translation inhibition mediated by EIF2A. By doing this, the virus uses the cellular defense for its own advantage: shutoff of cellular translation allows to produce big amounts of structural proteins needed for the virus to bud out of the doomed cell.1 Publication

Interactioni

Subunit structurei

P123 interacts with nsP4; nsP1, nsP2, nsP3 and nsP4 interact with each other, and with uncharacterized host factors.

Structurei

Secondary structure

1
2512
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni1013 – 10164Combined sources
Helixi1021 – 103212Combined sources
Helixi1039 – 10457Combined sources
Helixi1047 – 10504Combined sources
Helixi1057 – 106913Combined sources
Helixi1073 – 10753Combined sources
Beta strandi1079 – 10813Combined sources
Beta strandi1086 – 10883Combined sources
Beta strandi1098 – 11003Combined sources
Beta strandi1107 – 11093Combined sources
Helixi1112 – 11187Combined sources
Turni1119 – 11213Combined sources
Helixi1124 – 11274Combined sources
Turni1136 – 11383Combined sources
Beta strandi1141 – 11433Combined sources
Beta strandi1155 – 11595Combined sources
Helixi1174 – 11774Combined sources
Beta strandi1183 – 11886Combined sources
Beta strandi1198 – 12047Combined sources
Beta strandi1212 – 12143Combined sources
Helixi1217 – 12193Combined sources
Beta strandi1227 – 12326Combined sources
Helixi1242 – 126221Combined sources
Beta strandi1264 – 127512Combined sources
Helixi1280 – 129112Combined sources
Beta strandi1293 – 12997Combined sources
Beta strandi1310 – 13178Combined sources
Helixi1328 – 133811Combined sources
Beta strandi1351 – 13544Combined sources
Helixi1358 – 13603Combined sources
Beta strandi1363 – 13697Combined sources
Helixi1380 – 13878Combined sources
Helixi1389 – 13924Combined sources
Beta strandi1402 – 14076Combined sources
Beta strandi1410 – 14156Combined sources
Helixi1425 – 144521Combined sources
Beta strandi1449 – 14535Combined sources
Beta strandi1458 – 14603Combined sources
Turni1461 – 14644Combined sources
Helixi1468 – 147912Combined sources
Beta strandi1485 – 14895Combined sources
Helixi1493 – 150715Combined sources
Turni1531 – 15344Combined sources
Beta strandi1538 – 15414Combined sources
Beta strandi1543 – 15464Combined sources
Helixi1555 – 156713Combined sources
Helixi1571 – 158212Combined sources
Helixi1588 – 15936Combined sources
Beta strandi1609 – 16124Combined sources
Helixi1618 – 16269Combined sources
Beta strandi1632 – 16343Combined sources
Beta strandi1648 – 16503Combined sources
Beta strandi1654 – 16563Combined sources
Helixi1669 – 16724Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GUAX-ray2.85A/B/C1011-1675[»]
ProteinModelPortaliP03317.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 260231Alphavirus-like MTPROSITE-ProRule annotationAdd
BLAST
Domaini695 – 850156(+)RNA virus helicase ATP-bindingAdd
BLAST
Domaini851 – 999149(+)RNA virus helicase C-terminalAdd
BLAST
Domaini1012 – 1341330Peptidase C9PROSITE-ProRule annotationAdd
BLAST
Domaini1348 – 1507160MacroPROSITE-ProRule annotationAdd
BLAST
Domaini2266 – 2381116RdRp catalyticPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni245 – 26420nsP1 membrane-bindingBy similarityAdd
BLAST
Regioni1013 – 103220Nucleolus localization signalBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1196 – 12005Nuclear localization signalBy similarity

Sequence similaritiesi

Contains 1 alphavirus-like MT (methyltransferase) domain.PROSITE-ProRule annotation
Contains 1 Macro domain.PROSITE-ProRule annotation
Contains 1 peptidase C9 domain.PROSITE-ProRule annotation
Contains 1 RdRp catalytic domain.PROSITE-ProRule annotation

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR027351. (+)RNA_virus_helicase_core_dom.
IPR002588. Alphavirus-like_MT_dom.
IPR002620. Alphavirus_nsp2pro.
IPR002589. Macro_dom.
IPR027417. P-loop_NTPase.
IPR007094. RNA-dir_pol_PSvirus.
IPR029063. SAM-dependent_MTases.
IPR001788. Tymovirus_RNA-dep_RNA_pol.
[Graphical view]
PfamiPF01661. Macro. 1 hit.
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
[Graphical view]
SMARTiSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEiPS51743. ALPHAVIRUS_MT. 1 hit.
PS51154. MACRO. 1 hit.
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P03317-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKPVVNVDV DPQSPFVVQL QKSFPQFEVV AQQVTPNDHA NARAFSHLAS
60 70 80 90 100
KLIELEVPTT ATILDIGSAP ARRMFSEHQY HCVCPMRSPE DPDRMMKYAS
110 120 130 140 150
KLAEKACKIT NKNLHEKIKD LRTVLDTPDA ETPSLCFHND VTCNMRAEYS
160 170 180 190 200
VMQDVYINAP GTIYHQAMKG VRTLYWIGFD TTQFMFSAMA GSYPAYNTNW
210 220 230 240 250
ADEKVLEARN IGLCSTKLSE GRTGKLSIMR KKELKPGSRV YFSVGSTLYP
260 270 280 290 300
EHRASLQSWH LPSVFHLNGK QSYTCRCDTV VSCEGYVVKK ITISPGITGE
310 320 330 340 350
TVGYAVTHNS EGFLLCKVTD TVKGERVSFP VCTYIPATIC DQMTGIMATD
360 370 380 390 400
ISPDDAQKLL VGLNQRIVIN GRTNRNTNTM QNYLLPIIAQ GFSKWAKERK
410 420 430 440 450
DDLDNEKMLG TRERKLTYGC LWAFRTKKVH SFYRPPGTQT CVKVPASFSA
460 470 480 490 500
FPMSSVWTTS LPMSLRQKLK LALQPKKEEK LLQVSEELVM EAKAAFEDAQ
510 520 530 540 550
EEARAEKLRE ALPPLVADKG IEAAAEVVCE VEGLQADIGA ALVETPRGHV
560 570 580 590 600
RIIPQANDRM IGQYIVVSPN SVLKNAKLAP AHPLADQVKI ITHSGRSGRY
610 620 630 640 650
AVEPYDAKVL MPAGGAVPWP EFLALSESAT LVYNEREFVN RKLYHIAMHG
660 670 680 690 700
PAKNTEEEQY KVTKAELAET EYVFDVDKKR CVKKEEASGL VLSGELTNPP
710 720 730 740 750
YHELALEGLK TRPAVPYKVE TIGVIGTPGS GKSAIIKSTV TARDLVTSGK
760 770 780 790 800
KENCREIEAD VLRLRGMQIT SKTVDSVMLN GCHKAVEVLY VDEAFACHAG
810 820 830 840 850
ALLALIAIVR PRKKVVLCGD PMQCGFFNMM QLKVHFNHPE KDICTKTFYK
860 870 880 890 900
YISRRCTQPV TAIVSTLHYD GKMKTTNPCK KNIEIDITGA TKPKPGDIIL
910 920 930 940 950
TCFRGWVKQL QIDYPGHEVM TAAASQGLTR KGVYAVRQKV NENPLYAITS
960 970 980 990 1000
EHVNVLLTRT EDRLVWKTLQ GDPWIKQPTN IPKGNFQATI EDWEAEHKGI
1010 1020 1030 1040 1050
IAAINSPTPR ANPFSCKTNV CWAKALEPIL ATAGIVLTGC QWSELFPQFA
1060 1070 1080 1090 1100
DDKPHSAIYA LDVICIKFFG MDLTSGLFSK QSIPLTYHPA DSARPVAHWD
1110 1120 1130 1140 1150
NSPGTRKYGY DHAIAAELSR RFPVFQLAGK GTQLDLQTGR TRVISAQHNL
1160 1170 1180 1190 1200
VPVNRNLPHA LVPEYKEKQP GPVKKFLNQF KHHSVLVVSE EKIEAPRKRI
1210 1220 1230 1240 1250
EWIAPIGIAG ADKNYNLAFG FPPQARYDLV FINIGTKYRN HHFQQCEDHA
1260 1270 1280 1290 1300
ATLKTLSRSA LNCLNPGGTL VVKSYGYADR NSEDVVTALA RKFVRVSAAR
1310 1320 1330 1340 1350
PDCVSSNTEM YLIFRQLDNS RTRQFTPHHL NCVISSVYEG TRDGVGAAPS
1360 1370 1380 1390 1400
YRTKRENIAD CQEEAVVNAA NPLGRPGEGV CRAIYKRWPT SFTDSATETG
1410 1420 1430 1440 1450
TARMTVCLGK KVIHAVGPDF RKHPEAEALK LLQNAYHAVA DLVNEHNIKS
1460 1470 1480 1490 1500
VAIPLLSTGI YAAGKDRLEV SLNCLTTALD RTDADVTIYC LDKKWKERID
1510 1520 1530 1540 1550
AALQLKESVT ELKDEDMEID DELVWIHPDS CLKGRKGFST TKGKLYSYFE
1560 1570 1580 1590 1600
GTKFHQAAKD MAEIKVLFPN DQESNEQLCA YILGETMEAI REKCPVDHNP
1610 1620 1630 1640 1650
SSSPPKTLPC LCMYAMTPER VHRLRSNNVK EVTVCSSTPL PKHKIKNVQK
1660 1670 1680 1690 1700
VQCTKVVLFN PHTPAFVPAR KYIEVPEQPT APPAQAEEAP EVVATPSPST
1710 1720 1730 1740 1750
ADNTSLDVTD ISLDMDDSSE GSLFSSFSGS DNSITSMDSW SSGPSSLEIV
1760 1770 1780 1790 1800
DRRQVVVADV HAVQEPAPIP PPRLKKMARL AAARKEPTPP ASNSSESLHL
1810 1820 1830 1840 1850
SFGGVSMSLG SIFDGETARQ AAVQPLATGP TDVPMSFGSF SDGEIDELSR
1860 1870 1880 1890 1900
RVTESEPVLF GSFEPGEVNS IISSRSAVSF PLRKQRRRRR SRRTEYLTGV
1910 1920 1930 1940 1950
GGYIFSTDTG PGHLQKKSVL QNQLTEPTLE RNVLERIHAP VLDTSKEEQL
1960 1970 1980 1990 2000
KLRYQMMPTE ANKSRYQSRK VENQKAITTE RLLSGLRLYN SATDQPECYK
2010 2020 2030 2040 2050
ITYPKPLYSS SVPANYSDPQ FAVAVCNNYL HENYPTVASY QITDEYDAYL
2060 2070 2080 2090 2100
DMVDGTVACL DTATFCPAKL RSYPKKHEYR APNIRSAVPS AMQNTLQNVL
2110 2120 2130 2140 2150
IAATKRNCNV TQMRELPTLD SATFNVECFR KYACNDEYWE EFARKPIRIT
2160 2170 2180 2190 2200
TEFVTAYVAR LKGPKAAALF AKTYNLVPLQ EVPMDRFVMD MKRDVKVTPG
2210 2220 2230 2240 2250
TKHTEERPKV QVIQAAEPLA TAYLCGIHRE LVRRLTAVLL PNIHTLFDMS
2260 2270 2280 2290 2300
AEDFDAIIAE HFKQGDPVLE TDIASFDKSQ DDAMALTGLM ILEDLGVDQP
2310 2320 2330 2340 2350
LLDLIECAFG EISSTHLPTG TRFKFGAMMK SGMFLTLFVN TVLNVVIASR
2360 2370 2380 2390 2400
VLEERLKTSR CAAFIGDDNI IHGVVSDKEM AERCATWLNM EVKIIDAVIG
2410 2420 2430 2440 2450
ERPPYFCGGF ILQDSVTSTA CRVADPLKRL FKLGKPLPAD DEQDEDRRRA
2460 2470 2480 2490 2500
LLDETKAWFR VGITGTLAVA VTTRYEVDNI TPVLLALRTF AQSKRAFQAI
2510
RGEIKHLYGG PK
Length:2,512
Mass (Da):279,549
Last modified:July 21, 1986 - v1
Checksum:iF3656FC8BB495726
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02363 Genomic RNA. Translation: AAA96975.1. Sequence problems.
PIRiA03917. MNWVS.
RefSeqiNP_062889.1. NC_001547.1.

Genome annotation databases

GeneIDi1502154.
KEGGivg:1502154.

Keywords - Coding sequence diversityi

RNA suppression of termination

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02363 Genomic RNA. Translation: AAA96975.1. Sequence problems.
PIRiA03917. MNWVS.
RefSeqiNP_062889.1. NC_001547.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GUAX-ray2.85A/B/C1011-1675[»]
ProteinModelPortaliP03317.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiC09.001.

PTM databases

SwissPalmiP03317.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1502154.
KEGGivg:1502154.

Miscellaneous databases

PMAP-CutDBP03317.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR027351. (+)RNA_virus_helicase_core_dom.
IPR002588. Alphavirus-like_MT_dom.
IPR002620. Alphavirus_nsp2pro.
IPR002589. Macro_dom.
IPR027417. P-loop_NTPase.
IPR007094. RNA-dir_pol_PSvirus.
IPR029063. SAM-dependent_MTases.
IPR001788. Tymovirus_RNA-dep_RNA_pol.
[Graphical view]
PfamiPF01661. Macro. 1 hit.
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
[Graphical view]
SMARTiSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEiPS51743. ALPHAVIRUS_MT. 1 hit.
PS51154. MACRO. 1 hit.
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Complete nucleotide sequence of the genomic RNA of Sindbis virus."
    Strauss E.G., Rice C.M., Strauss J.H.
    Virology 133:92-110(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "The 5'-terminal sequences of the genomic RNAs of several alphaviruses."
    Ou J.H., Strauss E.G., Strauss J.H.
    J. Mol. Biol. 168:1-15(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-54.
  3. "Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon."
    Strauss E.G., Rice C.M., Strauss J.H.
    Proc. Natl. Acad. Sci. U.S.A. 80:5271-5275(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1429-2512.
  4. "Sequence studies of several alphavirus genomic RNAs in the region containing the start of the subgenomic RNA."
    Ou J.-H., Rice C.M., Dalgarno L., Strauss E.G., Strauss J.H.
    Proc. Natl. Acad. Sci. U.S.A. 79:5235-5239(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2431-2512.
  5. "Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes."
    Froshauer S., Kartenbeck J., Helenius A.
    J. Cell Biol. 107:2075-2086(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION OF NON-STRUCTURAL PROTEINS.
  6. "Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans."
    Hardy W.R., Strauss J.H.
    J. Virol. 63:4653-4664(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
  7. "Mutagenesis of the in-frame opal termination codon preceding nsP4 of Sindbis virus: studies of translational readthrough and its effect on virus replication."
    Li G.P., Rice C.M.
    J. Virol. 63:1326-1337(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-1896.
  8. "Cleavage-site preferences of Sindbis virus polyproteins containing the non-structural proteinase. Evidence for temporal regulation of polyprotein processing in vivo."
    de Groot R.J., Hardy W.R., Shirako Y., Strauss J.H.
    EMBO J. 9:2631-2638(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN BY NSP2.
  9. Cited for: UBIQUITIN DEGRADATION OF NSP4.
  10. "Identification of the active site residues in the nsP2 proteinase of Sindbis virus."
    Strauss E.G., De Groot R.J., Levinson R., Strauss J.H.
    Virology 191:932-940(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF CYS-1021; HIS-1098 AND TRP-1099.
  11. "Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis."
    Lemm J.A., Ruemenapf T., Strauss E.G., Strauss J.H., Rice C.M.
    EMBO J. 13:2925-2934(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus-strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus-strand RNA synthesis."
    Shirako Y., Strauss J.H.
    J. Virol. 68:1874-1885(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF P123.
  13. "Mutagenesis of the Sindbis virus nsP1 protein: effects on methyltransferase activity and viral infectivity."
    Wang H.-L., O'Rear J., Stollar V.
    Virology 217:527-531(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-39; HIS-81; ASP-91; ARG-94; TYR-249 AND ILE-369.
  14. "Requirement for an aromatic amino acid or histidine at the N-terminus of Sindbis virus RNA polymerase."
    Shirako Y., Strauss J.H.
    J. Virol. 72:2310-2315(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-1903.
  15. "Effects of palmitoylation of replicase protein nsP1 on alphavirus infection."
    Ahola T., Kujala P., Tuittila M., Blom T., Laakkonen P., Hinkkanen A., Auvinen P.
    J. Virol. 74:6725-6733(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-420, MUTAGENESIS OF CYS-420.
  16. "Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR."
    Ventoso I., Sanz M.A., Molina S., Berlanga J.J., Carrasco L., Esteban M.
    Genes Dev. 20:87-100(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  17. "Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II."
    Akhrymuk I., Kulemzin S.V., Frolova E.I.
    J. Virol. 86:7180-7191(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF NSP2.

Entry informationi

Entry nameiPOLN_SINDV
AccessioniPrimary (citable) accession number: P03317
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: February 17, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

The genome codes for P123, but readthrough of a terminator codon UGA occurs between the codons for Tyr-1896 and Leu-1897. This readthrough produces P1234, cleaved quickly by nsP2 into P123' and nsP4. Further processing of p123' gives nsP1, nsP2 and nsP3' which is 6 amino acids longer than nsP3 since the cleavage site is after the readthrough. This unusual molecular mechanism ensures that few nsP4 are produced compared to other non-structural proteins. Mutant viruses with no alternative termination site grow significantly slower than wild-type virus.

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.