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[1]
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NUCLEOTIDE SEQUENCE [GENOMIC RNA].
DOI=10.1128/JVI.76.12.6155-6163.2002; PubMed=12021349 [NCBI, ExPASy, EBI, Israel, Japan]
Weston J.H.,
Villoing S.,
Bremont M.,
Castric J.,
Pfeffer M.,
Jewhurst V.,
McLoughlin M.,
Rodseth O.,
Christie K.E.,
Koumans J.,
Todd D.;
"Comparison of two aquatic alphaviruses, Salmon pancreas disease virus and Sleeping disease virus, by using genome sequence analysis, monoclonal reactivity and cross-infection.";
J. Virol. 76:6155-6163(2002).
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- FUNCTION: P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex (By similarity).
- 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.
- 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: nsP3 is phosphorylated by host on serines and threonines (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: 2593 AA [This is the length of the unprocessed precursor] |
Molecular weight: 284853 Da [This is the MW of the unprocessed precursor] |
CRC64: 2E2B4F651A45B8CF [This is a checksum on the sequence] |
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10 20 30 40 50 60
MMLNLTANPS AGTTVTVDLP ADHPALNQFK TAFPGFEVVA SNRSSNDHAA ARAFSHLATK
70 80 90 100 110 120
WIERDIDGRQ VIVADIGSAP ARRVGAPDNV TYHSVCPRKC AEDPERLASY ARKLVRAVEK
130 140 150 160 170 180
GDGHLVSDRI TDLKDVLENP DTSLETTSIC LNDDVSCKVK ADIAVYQDVY AVDAPSTIYA
190 200 210 220 230 240
QADKGTRVVY WIGFEPFVFH TDAMAGSFPL YDANWSDSAV LAAKNLPLCY SGLSEDSIKW
250 260 270 280 290 300
RFRFRDKPLV PSGEIHYSVG STHYVEDRDK LKSWHLPSTF HFVAPNKYTC RCDTVVSCGG
310 320 330 340 350 360
YVVKKITICE GIVGRPANEE LATSYHRDGV VVTKFSDTIN HEQVSFPVVT YIPAVICDQM
370 380 390 400 410 420
TAMTADPVKY PDVVKLLVGL NQRIVVNGTT VRNVNSMDNS LIPVFARALC SWADEARRDM
430 440 450 460 470 480
EDEQDMYGVT SVTTWICICR AYDKRQQHTF YRRPKQSSGI YVPAKFTGSL RASLSATYLN
490 500 510 520 530 540
LPLKQLLLNT LKRAIKPGDQ ALADETEARA HDAAEVHELT EEEGRQQAAN PSYIADVLGQ
550 560 570 580 590 600
DDEEEVDDGM SNVDLGEEDG VGSTIIDCQR GTVKVITAFG DNTMGEYLVL SPVTVLRTRK
610 620 630 640 650 660
LAVLLGPLAE EVMQYVHKGR TGRYAIEKNN LKVLIPTGVS LKTAHFQALT ESATLTYNDY
670 680 690 700 710 720
LFTCRTLDQL ATRGSAKNTD EVYYKLVDAA KAKDEYVYEL SSKQCVKKED ATGTVLQGDI
730 740 750 760 770 780
CNPPYHQFAF EALRKRPAHT HDVHTIGIYG VPGAGKTAII TTEVTTRDLV ASGKKENCED
790 800 810 820 830 840
IKRCVLERRG LKIAARTVDS LLYGAYRGAV DTLYVDEAYA CHSGTLLALI AAVRPTGKVV
850 860 870 880 890 900
LCGDPKQVGC VNQLQMRMHY NHEISDRVLR KNISRRCTHT LTAIVSNLNY EGRMKTTNPC
910 920 930 940 950 960
KKPVLIDTTG STKPDKEALV LTCFRGWVKD LKILYPHNEL MTAAASQGLT REKVYAVRCR
970 980 990 1000 1010 1020
VTSNPLYEPT SEHITVLLTR TNDELVWKTL PNDPLIPILS KPPKGDYSAT MEDWEDEHNG
1030 1040 1050 1060 1070 1080
ILAALREACV PRMNFAHGKR NTCWAVTSSR VLHEAGVLIT PEDFNRIFPA FREDKPHSAL
1090 1100 1110 1120 1130 1140
AALDAVAALV WGLDTSSGIL SGKGSFMRLE NSHWSNSNRG YEYGLNLDAL EGYEIANPRM
1150 1160 1170 1180 1190 1200
IKALKQRRGR ECYDIETGKL VPMDPGRVQV PINRVVPHVL VDTSAAAKPG FLENRLSVDR
1210 1220 1230 1240 1250 1260
WDQVHSFKTR AAVKFAELTK RVSYNSVLDL GAARGGVTDY CVKKGKTVTC VSEQWDSKPR
1270 1280 1290 1300 1310 1320
GAVVITADIN GPLNNLGIFD LVFCDAAGPR RYHHYAQCED HARRSTSACK HGVERTAKGG
1330 1340 1350 1360 1370 1380
VFIVKAYGMA DRRTERAVEC TARYFKSVSV EKPVSSRITN VEVFFKFSGR CRPHARSIAH
1390 1400 1410 1420 1430 1440
LGPQLTDIYA RTRKAYKMLA RGSVADKVKV AEILNSMVGA APGYRVLNKN IITAEEEVLV
1450 1460 1470 1480 1490 1500
NAANSNGRPG DGVCGALYGA FGDAFPNGAI GAGNAVLVRG LEATIIHAAG ADFREVDEET
1510 1520 1530 1540 1550 1560
GARQLRAAYR AAATLVTANG ITSAAIPLLS THIFSNGRNR LEQSFGALVE AFDTTECDVT
1570 1580 1590 1600 1610 1620
IYCLANNMAA RIQQLIDDHA REEFDEEVVV EEEEEHEANA MCDTETLSSF GDETVWVPKH
1630 1640 1650 1660 1670 1680
STLAGRPGYS ATYGDRRSLF VGTKFHRAAV AMSSIEAAWP RTKEANAKLI EYIRGQHLVD
1690 1700 1710 1720 1730 1740
VLKSCPVNDI PVGRPPSSLP CGCIYAMTPE RVTVLKQRPQ EGFVVCSAFK LPLTNIQDVT
1750 1760 1770 1780 1790 1800
KVECTVRAPA EEPRPVRYLQ ERRPVQAAAR QPRPAIVAAS VAGTATSRRT PAPGSVQVRL
1810 1820 1830 1840 1850 1860
LPPRDGTVSR SSRTSSQSSV TSSAGPIMPV PRRAPVAPAA SLAGSVHSHS VRSAPAILRA
1870 1880 1890 1900 1910 1920
ASTGARSVRS VQSGLTGHRD DAVSVAGSVR QPSGPPSSVS TPAAPRGLTR EQFGAVRARA
1930 1940 1950 1960 1970 1980
RRDLELEGSE HGSQASFRSG SLVVGSTASS YSQRPDDQDT GSEPSGRGAA VRTRRRGQRD
1990 2000 2010 2020 2030 2040
GPGGYIFSSD QGTAHLSQHN TQTNNTTEVL MRTSVLPSND HGTPDLLAEM KKRLAYQMRP
2050 2060 2070 2080 2090 2100
TQKNKSRYLS AKVHNMKHKI VQCLQRGAGH YLREQHALPL WKNTFPKPRY SDACVVKFES
2110 2120 2130 2140 2150 2160
VNTAIVAANM FIGCNYPTLS SFGVTDKYDA YLDMVDGLNC NLDTVTFEPA KVRSLPKKSK
2170 2180 2190 2200 2210 2220
YNQPLIQSQV PGPMASTLQS ILMAATKRNC NVTQMRELPT MDSAAMNVEA FKKFACKDTD
2230 2240 2250 2260 2270 2280
LWTEFAEKPV RLSPGQIEEY VFHLQGAKAN VMHSRVEAAC PDLSEVAMDR FTLDMKRDVK
2290 2300 2310 2320 2330 2340
VTPGTKHVEE RPKVQVIQAA DPMATAYLCA IHRELVRRLK AVLKPSIHVL FDMSSEDFDA
2350 2360 2370 2380 2390 2400
IVGHGMKLGD KVLETDISSF DKSQDQAMAV TALMLLEDLG VEEDLLTLIE ASFGDITSVH
2410 2420 2430 2440 2450 2460
LPTGTRFQFG SMMKSGLFLT LFVNTLLNIT IAARVLREQL ADTRCAAFIG DDNVITGVVS
2470 2480 2490 2500 2510 2520
DDMMVARCAS WLNMEVKIME MEIGDRSPYF CGGFLLLDTV TGTVSRVSDP VKRLMKMGKP
2530 2540 2550 2560 2570 2580
ALNDPETDVD RCRALREEVE SWYRVGIQWP LQVAAATRYG VNHLPLATMA MATLAQDLRS
2590
YLGARGEYVS LYA
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Q8QL53 in FASTA format |
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