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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: 2601 AA [This is the length of the unprocessed precursor] |
Molecular weight: 285752 Da [This is the MW of the unprocessed precursor] |
CRC64: B052C737954909BE [This is a checksum on the sequence] |
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10 20 30 40 50 60
MMQNLTANPS AGATVTVNLP ADHPALNQFK TAFPGFEVVA SNRSSNDHAA ARAFSHLATK
70 80 90 100 110 120
WIERDIGGRQ VIVADIGSAP ARRIGAPDNV TYHSVCPRKC AEDPERLASY ARKLVRAVER
130 140 150 160 170 180
GDGHLVNEKI 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 GIVGIPAKEE LATSYHRDGV VVTKFSDTIN HEQVSFPVVT YIPAVICDQM
370 380 390 400 410 420
TAMTANPVKY SDAVKLLVGL NQRIVVNGTT VRNVNSMDNS LIPVFARALC SWADEVRRDM
430 440 450 460 470 480
EDEQDLYGIT SVTTWICICR AYDKRQQHTF YRRPKQSSGI YVPAKFTGSL RAALSATYLN
490 500 510 520 530 540
LPLKQLLLNT LKRAIKPMDQ AIADETEALA HDAAEVHELT EEERRQQAAN PSYIADVLGQ
550 560 570 580 590 600
DDDEEEAGDG MSDVDLGEED GAGATIIDCQ RGTVKVITAF GDNMMGEYLV LSPVTVLRTR
610 620 630 640 650 660
KLAILLGPLA EEVMQYVHKG RTGRYAIEKN NLKVLIPTGV SLKTDHFQAL AESATLTYND
670 680 690 700 710 720
YLFTCRTLDQ LATRGSARNT DEVYYKLVDA AKARDEYVYE LSSKQCVKKE DATGTVLQGD
730 740 750 760 770 780
ICNPPYHQFA YEALRKRPAH THDVHTIGIY GVPGAGKTAI ITTEVTTRDL VASGKKENCE
790 800 810 820 830 840
DIKRCVLERR GLKIAARTVD SLFYGAYRGA VNTLYVDEAY ACHSGTLLAL IAAVRPTGKV
850 860 870 880 890 900
VLCGDPKQVG CVNQLQMRMH YNHEISDRVL RKNISRRCTH TLTAIVSNLN YEGRMKTTNP
910 920 930 940 950 960
CKKPVLIDTT GSTKPDKEAL VLTCFRGWVK DLKFLYPHNE LMTAAASQGL TREKVYAVRC
970 980 990 1000 1010 1020
RVTTNPLYEP TSEHITVLLT RTNDELVWKT LPNDPLIPIL SKPPKGDYSA TMEDWEDEHN
1030 1040 1050 1060 1070 1080
GILAALREAC VPRMNFAHGK RNTCWAVTSS RVLHEAGVQI TPEDYNRIFP AFREDKPHSA
1090 1100 1110 1120 1130 1140
LAALDAVATL VWGLDTSSGI LSGKGSFMRL ENSHWSNSNR GYEYGLNLDA LEGYEIANPR
1150 1160 1170 1180 1190 1200
MIKALKQRRG RECYDIETGK LVPLDPARVQ VPINRIVPHV LVDTSAAAKP GFLENRLTVD
1210 1220 1230 1240 1250 1260
RWDQVHSFKT RAAVKFAELT KRVSYNSVLD LGAAPGGVTD YCVKKGKTVT SVSEQWDTKP
1270 1280 1290 1300 1310 1320
RGAVVVTADI NGPLNNLGIF DLVFCDAAGP RRYHHYAQCE DHAVLFTSAC KHGVERTAKG
1330 1340 1350 1360 1370 1380
GVFIVKAYGM ADRRTERAVE GTARYFRSVS VEKPVSSRIT NVEVFFKFSG RCRPHARSIA
1390 1400 1410 1420 1430 1440
HLGPQLTDIY ARTWKAYKML ARGSVADKVK VAEILNSMVG AAPGYRVLNR NIITAEEEVL
1450 1460 1470 1480 1490 1500
VNAANSNGRP GDGVCGALYG AFGDAFPNGA IGAGNAVLVR GLEATIIHAA GADFREVDEE
1510 1520 1530 1540 1550 1560
TGARQLRAAY RAAATLVTAN GITSAAIPLL STHIFSNGRN RLEQSFSALV EAFDTTECDV
1570 1580 1590 1600 1610 1620
TIYCLANNMA ARIQQLIDAH AREEFDEEVV VEEEEEHEAD AMSDTETLSS FGDETVWVPK
1630 1640 1650 1660 1670 1680
HSTLAGRPGY SAYYGDRRSL FVGTKFHRAA VAMSSIEAAW PKTKEANAKL IEYIRGQHLV
1690 1700 1710 1720 1730 1740
DVLKSCPVDD IPVGRPPSSL PCGCIYAMTP ERVTVLKQRP QEGFVVCSAF KLPLTNIQDV
1750 1760 1770 1780 1790 1800
TKVECTVRAP AEEPRPVRHL QERRPAQAAV RQLRPAAVAA SVAASHTASR TSTASSRRTP
1810 1820 1830 1840 1850 1860
APGSVQVRLL PPRDGTESRS SRMGSQSSVT SSAGSVPPAP RRAPAVSAAS LASSAHSRSV
1870 1880 1890 1900 1910 1920
RSAPAMRAAS AGARSVRSAQ SGSTGHRAGA FSVAGSVRQP SGPPSSVSTP AAIRGLTRDQ
1930 1940 1950 1960 1970 1980
FDAVRVRARR NLELEGSEHG SQSSFHSGSL AVGSSASSYS QRSDDQDTGT EPSSRGAAVR
1990 2000 2010 2020 2030 2040
TRRRGQRDGL GGYIFSSDQG TAHLSQHNTQ TNNTTEVLMR TSVLPSNDHG TPDLPAETRK
2050 2060 2070 2080 2090 2100
RLAYQMRPTQ KNKSRYLSAK VHNMKHKIVR CLQRGAGHYL REQHALPLWK NTFPKPRYSD
2110 2120 2130 2140 2150 2160
ACVVKFESVN TAIVAANMFI GCNYPTLSSF GITDKYDAYL DMVDGLNCNL DTVTFDPAKV
2170 2180 2190 2200 2210 2220
RSLPKKSEYN QPLIQSQVPG PMTSTLQSIL MAATKRNCNV TQMRELPTMD SAAMNVEAFK
2230 2240 2250 2260 2270 2280
SFACKDTDLW TEFAEKPVRL SPGQIEEYVF HLQGAKANVM HSRVEAVCPD LSEVAMDRFT
2290 2300 2310 2320 2330 2340
LDMKRDVKVT PGTKHVEERP KVQEIQAADP MATAYLCAIH RELVRRLKAV LKPSIHVLFD
2350 2360 2370 2380 2390 2400
MSSEDFDAIV GHGMKLGDKV LETDISSFDK SQDQAMAVTA LMLLRDLGVE EDLLTLIEAS
2410 2420 2430 2440 2450 2460
FGDITSAHLP TGTRFQFGSM MKSGLFLTLF VNTLLNITIA ARVLREQLAD TRCAAFIGDD
2470 2480 2490 2500 2510 2520
NVITGVVSDD MMVARCASWL NMEVKIMDME IGNMSPYFCG GFLLLDTVTG TVSRVSDPVK
2530 2540 2550 2560 2570 2580
RLMKMGKPAL NDPETDVDRC RALREEVESW YRVGIQWPLQ VAAATRYGVN HLPLATMAMA
2590 2600
TLAQDLRSYL GARGEYVSLY V
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Q8JJX1 in FASTA format |
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