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[1]
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NUCLEOTIDE SEQUENCE [GENOMIC RNA].
DOI=10.1016/0042-6822(90)90191-S; PubMed=2155505 [NCBI, ExPASy, EBI, Israel, Japan]
Levinson R.S.,
Strauss J.H.,
Strauss E.G.;
"Complete sequence of the genomic RNA of O'nyong-nyong virus and its use in the construction of alphavirus phylogenetic trees.";
Virology 175:110-123(1990).
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[2]
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NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1334-2514.
DOI=10.1016/0042-6822(88)90644-7; PubMed=2834873 [NCBI, ExPASy, EBI, Israel, Japan]
Strauss E.G.,
Levinson R.,
Rice C.M.,
Dalrymple J.,
Strauss J.H.;
"Nonstructural proteins nsP3 and nsP4 of Ross River and O'Nyong-nyong viruses: sequence and comparison with those of other alphaviruses.";
Virology 164:265-274(1988).
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- FUNCTION: 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 (By similarity).
- FUNCTION: 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 (By similarity).
- FUNCTION: nsP3 is essential for minus strand and subgenomic 26S mRNA synthesis (By similarity).
- FUNCTION: nsP4 is a 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 encodes for structural proteins (By similarity).
- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + GTP = m7GTP.
- CATALYTIC ACTIVITY: m7GTP + (5')pp-Pur-mRNA = diphosphate + m7G(5')ppp-Pur-mRNA.
- CATALYTIC ACTIVITY: (5')ppp-mRNA + H2O = (5')pp-mRNA + phosphate.
- CATALYTIC ACTIVITY: A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.
- CATALYTIC ACTIVITY: NTP + H2O = NDP + phosphate.
- CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
- SUBUNIT: P123 interacts with nsP4; nsP1, nsP2, nsP3 and nsP4 interact with each other, and with uncharacterized host factors (By similarity).
- SUBCELLULAR LOCATION: Non-structural polyprotein: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Note=Located on the cytoplasmic surface of modified endosomes and lysosomes, also called cytopathic vacuoles type I (CPVI). These vacuoles contain numerous small circular invaginations (spherules) which may be the sites of RNA synthesis.
- SUBCELLULAR LOCATION: P123: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity).
- SUBCELLULAR LOCATION: mRNA-capping enzyme nsP1: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Cell membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then a fraction of nsP1 localizes to the inner surface of the plasma membrane (By similarity).
- SUBCELLULAR LOCATION: Protease/triphosphatase/NTPase/helicase nsP2: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Nucleus (By similarity). Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then approximately half of nsP2 is found in the nucleus (By similarity).
- SUBCELLULAR LOCATION: Non-structural protein 3: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Cytoplasm (By similarity). Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' seems to aggregate in cytoplasm (By similarity).
- SUBCELLULAR LOCATION: RNA-directed RNA polymerase nsP4: Endosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Lysosome membrane; Peripheral membrane protein; Cytoplasmic side (By similarity).
- INDUCTION: Viral replication produces dsRNA in the late phsae 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.
- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The polyprotein is synthesized as P1234 by stop codon readthrough. This polyprotein is 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 and nsP4 start to replicate the viral genome into its antigenome. After these early events, nsP1 is cleaved in cis by nsP2 protease, releasing P23 polyprotein. Cleavage of nsP1 exposes an 'activator' at the N-terminus of 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 (By similarity).
- PTM: nsP1 is palmitoylated by host (By similarity).
- PTM: nsP4 is ubiquitinated; targets the protein for rapid degradation via the ubiquitin system (By similarity).
- SIMILARITY: Contains 1 Macro domain.
- SIMILARITY: Contains 1 peptidase C9 domain [view classification].
- SIMILARITY: Contains 1 RdRp catalytic domain.
- CAUTION: There is no stop codon readthrough before nsP4.
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Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms.
Distributed under the Creative Commons Attribution-NoDerivs License.
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| Length: 2514 AA [This is the length of the unprocessed precursor] |
Molecular weight: 280117 Da [This is the MW of the unprocessed precursor] |
CRC64: 370B374690530F21 [This is a checksum on the sequence] |
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10 20 30 40 50 60
MDSVYVDIDA DSAFLKALQQ AYPMFEVEPK QVTPNDHANA RAFSHLAIKL IEQEIDPDST
70 80 90 100 110 120
ILDIGSAPAR RMMSDRKYHC VCPMRSAEDP ERLANYARKL ASAAGKVTDK NISGKINDLQ
130 140 150 160 170 180
AVMAVPNMET STFCLHTDAT CKQRGDVAIY QDVYAVHAPT SLYHQAIKGV RVAYWIGFDT
190 200 210 220 230 240
TPFMYNAMAG AYPSYSTNWA DEQVLKAKNI GLCSTDLSEG RRGKLSIMRG KKLKPCDRVL
250 260 270 280 290 300
FSVGSTLYPE SRKLLQSWHL PSVFHLKGKL SFTCRCDTIV SCEGYVVKRV TMSPGIYGKT
310 320 330 340 350 360
SGYAVTHHAG GFLMCKTTDT VDGERVSFSV CTYVPATICD QMTGILATEV TPEDAQKLLV
370 380 390 400 410 420
GLNQRIVVNG RTQRNTNTMK NYLLPIVAQA FSKWAKECRK DMEDEKLLGV RERTLTCCCL
430 440 450 460 470 480
WAFRKHKTHT VYKRPDTQSI QKVPAEFDSF VIPSLWSSGL SIPLRTRIKW LLSKAPKYEQ
490 500 510 520 530 540
LPHSGNAEEA AQAETDAVEE QEAELTREAM PPLQATQDDI QVEIDVEQLE DRAGAGIVET
550 560 570 580 590 600
PRGAIKVTAQ PSDLVVGEYL VLTPQAVLRS QKLSLIHALA EQVKTCTHSG RAGRYAVEAY
610 620 630 640 650 660
DGRVLVPSGY AIPQEDFQSL SESATMVFNE REFVNRKLHH IAMHGPALNT DEESYELVRV
670 680 690 700 710 720
EKTEHEYVYD VDQKKCCKRE EATGLVLVGD LTSPPYHEFA YEGLKIRPAC PYKTAVIGVF
730 740 750 760 770 780
GVPGSGKSAI IKNLVTRQDL VTSGKKENCQ EISNDVMRQR KLEISARTVD SLLLNGCNKP
790 800 810 820 830 840
VEVLYVDEAF ACHSGTLLAL IAMVRPRQKV VLCGDPKQCG FFNMMQMKVN YNHNICTQVY
850 860 870 880 890 900
HKSISRRCTL PVTAIVSSLH YESKMRTTNE YNQPIVVDTT GITKPEPGDL VLTCFRGWVK
910 920 930 940 950 960
QLQIDYRGNE VMTAAASQGL TRKGVYAVRQ KVNENPLYAP TSEHVNVLLT RTEGKLTWKT
970 980 990 1000 1010 1020
LSGDPWIKIL QNPPKGDFKA TIKEWEAEHA SIMAGICNHQ MAFDTFQNKA NVCWAKCLVP
1030 1040 1050 1060 1070 1080
ILDTAGIKLS DRQWSQIVQA FKEDRAYSPE VALNEICTRI YGVDLDSGLF SKPLISVYYA
1090 1100 1110 1120 1130 1140
DNHWDNRPGG KMFGFNPEVA LMLEKKYPFT KGKWNINKQI CITTRKVDEF NPETNIIPAN
1150 1160 1170 1180 1190 1200
RRLPHSLVAE HHSVRGERME WLVNKISGHH MLLVSGHNLI LPTKRVTWVA PLGTRGADYT
1210 1220 1230 1240 1250 1260
YNLELGLPAT LGRYDLVVIN IHTPFRIHHY QQCVDHAMKL QMLGGDSLRL LKPGGSLLIR
1270 1280 1290 1300 1310 1320
AYGYADRTSE RVISVLGRKF RSSRALKPQC ITSNTEMFFL FSRFDNGRRN FTTHVMNNQL
1330 1340 1350 1360 1370 1380
NAVYAGLATR AGCAPSYRVK RMDIAKNTEE CVVNAANPRG VPGDGVCKAV YRKWPESFRN
1390 1400 1410 1420 1430 1440
SATPVGTAKT IMCGQYPVIH AVGPNFSNYS EAEGDRELAS VYREVAKEVS RLGVSSVAIP
1450 1460 1470 1480 1490 1500
LLSTGVYSGG KDRLLQSLNH LFAAMDSTDA DVVIYCRDKE WEKKITEAIS LRSQVELLDD
1510 1520 1530 1540 1550 1560
HISVDCDIVR VHPDSSLAGR KGYSTVEGAL YSYLEGTRFH QTAVDMAEIY TMWPKQTEAN
1570 1580 1590 1600 1610 1620
EQVCLYALGE SIESVRQKCP VDDADASFPP KTVPCLCRYA MTPERVARLR MNHTTSIIVC
1630 1640 1650 1660 1670 1680
SSFPLPKYKI EGVQKVKCSK ALLFDHNVPS RVSPRTYRPA DEIIQTPQTP TEACQDAQLV
1690 1700 1710 1720 1730 1740
QSINDEAVPV PSDLEACDAT MDWPSIGTVS TRQRHDSSDS EYSGSRSNIQ LVTADVHAPM
1750 1760 1770 1780 1790 1800
YAHSLASSGG SMLSLSSEPA QNGTMILLDS EDTDSISRVS TPIAPPRRRL GRTINVTCDE
1810 1820 1830 1840 1850 1860
REGKILPMAS DRFFTAKPYT VALSVSTADM TVYPIQAPLG LIPPPTLEPI TFGDFAEGEI
1870 1880 1890 1900 1910 1920
DNLLTGALTF GDFEPGEVEE LTDSEWSTCS DTDEELRLDR AGGYIFSSDT GQGHLQQKSV
1930 1940 1950 1960 1970 1980
RQTTLPVNIV EEVHEEKCYP PKLDEIKEQL LLKRLQESAS TANRSRYQSR KVENMKATII
1990 2000 2010 2020 2030 2040
HRLKEGCRLY LASETPRVPS YRVTYPAPIY SPSINIKLTN PETAVAVCNE FLARNYPTVA
2050 2060 2070 2080 2090 2100
SYQVTDEYDA YLDMVDGSES CLDRATFNPS KLRSYPKQHS YHAPTIRSAV PSPFQNTLQN
2110 2120 2130 2140 2150 2160
VLAAATKRNC NVTQMRELPT MDSAVFNVEC FKKYACNQEY WREFASSPIR VTTENLTMYV
2170 2180 2190 2200 2210 2220
TKLKGPKAAA LFAKTHNLLP LQEVPMDRFT MDMKRDVKVT PGTKHTEERP KVQVIQAAEP
2230 2240 2250 2260 2270 2280
LATAYLCGIH RELVRRLNAV LLPNVHTLFD MSAEDFDAII ATHFKPGDAV LETDIASFDK
2290 2300 2310 2320 2330 2340
SQDDSLASTA MMLLEDLGVD QPILDLIEAA FGEISSCHLP TGTRFKFGAM MKSGMFLTLF
2350 2360 2370 2380 2390 2400
VNTLLNITIA SRVLEERLTT SACAAFIGDD NIIHGVVSDA LMAARCATWM NMEVKIIDAV
2410 2420 2430 2440 2450 2460
VSEKAPYFCG GFILHDTVTG TSCRVADPLK RLFKLGKPLA AGDEQDEDRR RALADEVTRW
2470 2480 2490 2500 2510
QRTGLVTELE KAVYSRYEVQ GITAVITSMA TFANSKENFK KLRGPVVTLY GGPK
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P13886 in FASTA format |
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