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Protein

Non-structural polyprotein

Gene
N/A
Organism
Getah virus (GETV)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 (By similarity).By similarity
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).By similarity
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 (By similarity).By similarity
nsP3 and nsP3' are essential for minus strand and subgenomic 26S mRNA synthesis.By similarity
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 (By similarity).By similarity

Miscellaneous

The genome codes for P123, but readthrough of a terminator codon UGA occurs between the codons for Ser-1849 and Leu-1850. 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.

Catalytic activityi

S-adenosyl-L-methionine + GTP = m7GTP.
m7GTP + [nsP1 protein] = m7GMP-[nsP1 protein] + diphosphate.
m7GMP-[nsP1 protein] + (5')pp-Pur-mRNA = m7G(5')ppp-Pur-mRNA + [nsP1 protein].
(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)DescriptionActionsGraphical viewLength
Active sitei1012For cysteine protease nsP2 activityPROSITE-ProRule annotation1
Active sitei1081For cysteine protease nsP2 activityPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi720 – 727ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, Methyltransferase, Multifunctional enzyme, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed RNA polymerase, Thiol protease, Transferase
Biological processEukaryotic 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
LigandATP-binding, GTP-binding, Nucleotide-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
OrganismiGetah virus (GETV)
Taxonomic identifieri59300 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirus
Virus hostiAedes vexans (Inland floodwater mosquito) (Culex vexans) [TaxID: 7163]
Culex tritaeniorhynchus (Mosquito) [TaxID: 7178]
Equus caballus (Horse) [TaxID: 9796]
Proteomesi
  • UP000008625 Componenti: Genome

Subcellular locationi

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

GO - Cellular componenti

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003083921 – 2466Non-structural polyproteinAdd BLAST2466
ChainiPRO_00002287731 – 1855P123'Add BLAST1855
ChainiPRO_00002287741 – 1849P123Add BLAST1849
ChainiPRO_00002287751 – 534mRNA-capping enzyme nsP1Add BLAST534
ChainiPRO_0000228776535 – 1332Protease nsP2Add BLAST798
ChainiPRO_00002287771333 – 1855Non-structural protein 3'Add BLAST523
ChainiPRO_00002287781333 – 1849Non-structural protein 3Add BLAST517
ChainiPRO_00002287791856 – 2466RNA-directed RNA polymerase nsP4Add BLAST611

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi416S-palmitoyl cysteine; by hostBy similarity1
Lipidationi418S-palmitoyl cysteine; by hostBy similarity1

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 (By similarity).By similarity
nsP1 is palmitoylated by host.By similarity
nsP4 is ubiquitinated; targets the protein for rapid degradation via the ubiquitin system.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei534 – 535Cleavage; by nsP2By similarity2
Sitei1332 – 1333Cleavage; by nsP2By similarity2
Sitei1855 – 1856Cleavage; by nsP2By similarity2

Keywords - PTMi

Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PRIDEiQ5Y389

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.

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ5Y389
SMRiQ5Y389
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 258Alphavirus-like MTPROSITE-ProRule annotationAdd BLAST232
Domaini689 – 841(+)RNA virus helicase ATP-bindingAdd BLAST153
Domaini842 – 990(+)RNA virus helicase C-terminalAdd BLAST149
Domaini1003 – 1325Peptidase C9PROSITE-ProRule annotationAdd BLAST323
Domaini1333 – 1492MacroPROSITE-ProRule annotationAdd BLAST160
Domaini2220 – 2335RdRp catalyticPROSITE-ProRule annotationAdd BLAST116

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni243 – 262nsP1 membrane-bindingBy similarityAdd BLAST20
Regioni1004 – 1023Nucleolus localization signalBy similarityAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1180 – 1184Nuclear localization signalBy similarity5

Phylogenomic databases

OrthoDBiVOG09000007

Family and domain databases

InterProiView protein in InterPro
IPR027351 (+)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
IPR001788 Tymovirus_RNA-dep_RNA_pol
PfamiView protein in Pfam
PF01661 Macro, 1 hit
PF01707 Peptidase_C9, 1 hit
PF00978 RdRP_2, 1 hit
PF01443 Viral_helicase1, 1 hit
PF01660 Vmethyltransf, 1 hit
SMARTiView protein in SMART
SM00506 A1pp, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51743 ALPHAVIRUS_MT, 1 hit
PS51154 MACRO, 1 hit
PS51520 NSP2PRO, 1 hit
PS51657 PSRV_HELICASE, 1 hit
PS50507 RDRP_SSRNA_POS, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q5Y389-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKVTVDVEAD SPFLKALQKA FPAFEVESQQ VTPNDHANAR AFSHLATKLI
60 70 80 90 100
EQEVPTGVTI LDVGSAPARR LMSDHTYHCI CPMKSAEDPE RLANYARKLA
110 120 130 140 150
KASGTVLDKN VSGKITDLQD VMATPDLESP TFCLHTDETC RTRAEVAVYQ
160 170 180 190 200
DVYAVHAPTS LYHQAIKGVR TAYWIGFDTT PFMFEALAGA YPAYSTNWAD
210 220 230 240 250
EQVLQARNIG LCATGLSEGR RGKLSIMRKK CLRPSDRVMF SVGSTLYTES
260 270 280 290 300
RKLLRSWHLP SVFHLKGKNS FTCRCDTVVS CEGYVVKKIT ISPGIYGKTV
310 320 330 340 350
DYAVTHHAEG FLMCKITDTV RGERVSFPVC TYVPATICDQ MTGILATDVT
360 370 380 390 400
PEDAQKLLVG LNQRIVVNGR TQRNTNTMKN YLLPVVAQAF SKWAREARAD
410 420 430 440 450
MEDEKPLGTR ERTLTCCCLW AFKSHKIHTM YKRPETQTIV KVPSTFDSFV
460 470 480 490 500
IPSLWSSSLS MGIRQRIKLL LSARMAQGLP YSGDRTEARA AEEEEKEVQE
510 520 530 540 550
AELTRAALPP LVSGSCADDI AQVDVEELTF RAGAGVVETP RNALKVTPQA
560 570 580 590 600
HDHLIGSYLI LSPQTVLKSE KLAPIHPLAE QVTVMTHSGR SGRYPVDKYD
610 620 630 640 650
GRVLIPTGAA IPVSEFQALS ESATMVYNER EFINRKLHHI ALYGPALNTD
660 670 680 690 700
EESYEKVRAE RAETEYVFDV DKKACIKKEE ASGLVLTGDL INPPFHEFAY
710 720 730 740 750
EGLKIRPAAP YHTTIIGVFG VPGSGKSAII KNMVTTRDLV ASGKKENCQE
760 770 780 790 800
IMNDVKRQRG LDVTARTVDS ILLNGCKKGV ENLYVDEAFA CHSGTLLALI
810 820 830 840 850
ALVRPSGKVV LCGDPKQCGF FNLMQLKVHY NHNICTRVLH KSISRRCTLP
860 870 880 890 900
VTAIVSTLHY QGKMRTTNRC NTPIQIDTTG SSKPASGDIV LTCFRGWVKQ
910 920 930 940 950
LQIDYRGHEV MTAAASQGLT RKGVYAVRQK VNENPLYSPL SEHVNVLLTR
960 970 980 990 1000
TENRLVWKTL SGDPWIKVLT NVPRGDFSAT LEEWHEEHDG IMRVLNERPA
1010 1020 1030 1040 1050
EVDPFQNKAK VCWAKCLVQV LETAGIRMTA DEWNTILAFR EDRAYSPEVA
1060 1070 1080 1090 1100
LNEICTRYYG VDLDSGLFSA QSVSLFYENN HWDNRPGGRM YGFNHEVARK
1110 1120 1130 1140 1150
YAARFPFLRG NMNSGLQLNV PERKLQPFSA ECNIVPSNRR LPHALVTSYQ
1160 1170 1180 1190 1200
QCRGERVEWL LKKIPGHQML LVSEYNLVIP HKRVFWIAPP RVSGADRTYD
1210 1220 1230 1240 1250
LDLGLPMDAG RYDLVFVNIH TEYRQHHYQQ CVDHSMRLQM LGGDSLHLLR
1260 1270 1280 1290 1300
PGGSLLMRAY GYADRVSEMV VTALARKFSA FRVLRPACVT SNTEVFLLFS
1310 1320 1330 1340 1350
NFDNGRRAVT LHQANQKLSS MYACNGLHTA GCAPSYRVRR ADISGHSEEA
1360 1370 1380 1390 1400
VVNAANAKGT VSDGVCRAVA KKWPSSFKGA ATPVGTAKMI RADGMTVIHA
1410 1420 1430 1440 1450
VGPNFSTVTE AEGDRELAAA YRAVASIIST NNIKSVAVPL LSTGTFSGGK
1460 1470 1480 1490 1500
DRVMQSLNHL FTALDATDAD VVIYCRDKNW EKKIQEAIDR RTAIELVSED
1510 1520 1530 1540 1550
VTLETDLVRV HPDSCLVGRN GYSATDGKLY SYLEGTRFHQ TAVDMAEIST
1560 1570 1580 1590 1600
LWPRLQDANE QICLYALGET MDSIRTKCPV EDADSSTPPK TVPCLCRYAM
1610 1620 1630 1640 1650
TAERVARLRM NNTKNIIVCS SFPLPKYRIE GVQKVKCDRV LIFDQTVPSL
1660 1670 1680 1690 1700
VSPRKYIQQP PEQLDNVSLT STTSTGSAWS FPSETTYETM EVVAEVHTEP
1710 1720 1730 1740 1750
PIPPPRRRRA AVAQLRQDLE VTEEIEPYVT QQAEIMVMER VATTDIRAIP
1760 1770 1780 1790 1800
VPARRAITMP VPAPRVRKVA TEPPLEPEAP IPAPRKRRTT STSPPHNPED
1810 1820 1830 1840 1850
FVPRVPVELP WEPEDLDIQF GDLEPRRRNT RDRDVSTGIQ FGDIDFNQSL
1860 1870 1880 1890 1900
GRAGAYIFSS DTGPGHLQQK SVRQHELPCE TLYAHEDERI YPPAFDGEKE
1910 1920 1930 1940 1950
KVLQAKMQMA PTEANKSRYQ SRKVENMKAL IVERLREGAK LYLHEQTDKV
1960 1970 1980 1990 2000
PTYTSKYPRP VYSPSVDDSL SDPEVAVAAC NSFLEENYPT VANYQITDEY
2010 2020 2030 2040 2050
DAYLDLVDGS ESCLDRATFC PAKLRCYPKH HAYHQPQIRS AVPSPFQNTL
2060 2070 2080 2090 2100
QNVLAAATKR NCNVTQMREL PTMDSAVFNV ESFKKYACTG EYWQEFKDNP
2110 2120 2130 2140 2150
IRITTENITT YVAKLKGPKA AALFAKTHNL VPLQEVPMDR FVMDMKRDVK
2160 2170 2180 2190 2200
VTPGTKHTEE RPKVQVIQAA EPLATAYLCG IHRELVRRLK AVLTPNIHTL
2210 2220 2230 2240 2250
FDMSAEDFDA IIAAHFQPGD AVLETDIASF DKSQDDSLAL TALMLLEDLG
2260 2270 2280 2290 2300
VDQELLDLIE AAFGEITSVH LPTGTRFKFG AMMKSGMFLT LFINTLLNIV
2310 2320 2330 2340 2350
IACRVLRDKL SSSACAAFIG DDNIVHGVRS DPLMAERCAS WVNMEVKIID
2360 2370 2380 2390 2400
ATMCEKPPYF CGGFILYDSV AGTACRVADP LKRLFKLGKP LPADDNQDED
2410 2420 2430 2440 2450
RRRALKDETV KWSRIGLREE LDVALSSRYQ VSGVGNITRA MSTLSKSLKS
2460
FRKIRGPIIH LYGGPK
Length:2,466
Mass (Da):275,210
Last modified:March 21, 2006 - v2
Checksum:i5870CF4316BEFB79
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY702913 Genomic RNA Translation: AAU85259.1
RefSeqiYP_164438.1, NC_006558.1

Genome annotation databases

GeneIDi5075854
KEGGivg:5075854

Keywords - Coding sequence diversityi

RNA suppression of termination

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY702913 Genomic RNA Translation: AAU85259.1
RefSeqiYP_164438.1, NC_006558.1

3D structure databases

ProteinModelPortaliQ5Y389
SMRiQ5Y389
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiC09.001

Proteomic databases

PRIDEiQ5Y389

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi5075854
KEGGivg:5075854

Phylogenomic databases

OrthoDBiVOG09000007

Family and domain databases

InterProiView protein in InterPro
IPR027351 (+)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
IPR001788 Tymovirus_RNA-dep_RNA_pol
PfamiView protein in Pfam
PF01661 Macro, 1 hit
PF01707 Peptidase_C9, 1 hit
PF00978 RdRP_2, 1 hit
PF01443 Viral_helicase1, 1 hit
PF01660 Vmethyltransf, 1 hit
SMARTiView protein in SMART
SM00506 A1pp, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS51743 ALPHAVIRUS_MT, 1 hit
PS51154 MACRO, 1 hit
PS51520 NSP2PRO, 1 hit
PS51657 PSRV_HELICASE, 1 hit
PS50507 RDRP_SSRNA_POS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPOLN_GETV
AccessioniPrimary (citable) accession number: Q5Y389
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: March 21, 2006
Last modified: April 25, 2018
This is version 96 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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