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UniProtKB - Q5XXP4 (POLN_CHIK3)

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Protein

Non-structural polyprotein

Gene
N/A
Organism
Chikungunya virus (strain 37997) (CHIKV)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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).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 is 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 (By similarity).By similarity

Caution

There is no stop codon readthrough before nsP4.Curated

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 sitei1013For cysteine protease nsP2 activityPROSITE-ProRule annotation1
Active sitei1083For cysteine protease nsP2 activityPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi721 – 728ATPSequence analysis8

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural polyprotein
Alternative name(s):
Polyprotein nsP1234
Short name:
P1234
Cleaved into the following 5 chains:
P123
mRNA-capping enzyme nsP1 (EC:2.1.1.-, EC:2.7.7.-)
Alternative name(s):
Non-structural protein 1
Protease nsP2 (EC:3.1.3.33, EC:3.4.22.-, EC:3.6.1.15, EC:3.6.4.13)
Alternative name(s):
Non-structural protein 2
Short name:
nsP2
Non-structural protein 3
Short name:
nsP3
RNA-directed RNA polymerase nsP4 (EC:2.7.7.48)
Alternative name(s):
Non-structural protein 4
Short name:
nsP4
OrganismiChikungunya virus (strain 37997) (CHIKV)
Taxonomic identifieri371095 [NCBI]
Taxonomic lineageiViruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus ›
Virus hostiAedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159]
Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta) [TaxID: 7160]
Aedes furcifer (Mosquito) [TaxID: 299627]
Aedes polynesiensis (Polynesian tiger mosquito) [TaxID: 188700]
Cercopithecus [TaxID: 9533]
Homo sapiens (Human) [TaxID: 9606]
Macaca (macaques) [TaxID: 9539]
Pan troglodytes (Chimpanzee) [TaxID: 9598]
Papio (baboons) [TaxID: 9554]
Presbytis [TaxID: 9573]
Proteomesi
  • UP000008450 Componenti: Genome

Subcellular locationi

Non-structural polyprotein :
P123 :
mRNA-capping enzyme nsP1 :
Protease nsP2 :
Non-structural protein 3 :
RNA-directed RNA polymerase nsP4 :

GO - Cellular componenti

View the complete GO annotation on QuickGO ...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003083961 – 2474Non-structural polyproteinAdd BLAST2474
ChainiPRO_00002277651 – 1863P123By similarityAdd BLAST1863
ChainiPRO_00002277661 – 535mRNA-capping enzyme nsP1By similarityAdd BLAST535
ChainiPRO_0000227767536 – 1333Protease nsP2By similarityAdd BLAST798
ChainiPRO_00002277681334 – 1863Non-structural protein 3By similarityAdd BLAST530
ChainiPRO_00002277691864 – 2474RNA-directed RNA polymerase nsP4By similarityAdd BLAST611

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi417S-palmitoyl cysteine; by hostBy similarity1
Lipidationi419S-palmitoyl cysteine; by hostBy similarity1

Post-translational modificationi

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).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
Sitei535 – 536Cleavage; by nsP2By similarity2
Sitei1333 – 1334Cleavage; by nsP2By similarity2
Sitei1863 – 1864Cleavage; by nsP2By similarity2

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ5XXP4

Expressioni

Inductioni

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.

Interactioni

Subunit structurei

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

Structurei

3D structure databases

ProteinModelPortaliQ5XXP4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 259Alphavirus-like MTPROSITE-ProRule annotationAdd BLAST232
Domaini690 – 842(+)RNA virus helicase ATP-bindingAdd BLAST153
Domaini843 – 991(+)RNA virus helicase C-terminalAdd BLAST149
Domaini1004 – 1327Peptidase C9PROSITE-ProRule annotationAdd BLAST324
Domaini1334 – 1493MacroPROSITE-ProRule annotationAdd BLAST160
Domaini2228 – 2343RdRp catalyticPROSITE-ProRule annotationAdd BLAST116

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni244 – 263nsP1 membrane-bindingBy similarityAdd BLAST20
Regioni1005 – 1024Nucleolus localization signalBy similarityAdd BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1182 – 1186Nuclear 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.

Q5XXP4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPVYVDIDA DSAFLKALQR AYPMFEVEPR QVTPNDHANA RAFSHLAIKL 
        60         70         80         90        100
IEQEIDPDST ILDIGSAPAR RMMSDRKYHC VCPMRSAEDP ERLANYARKL 
       110        120        130        140        150
ASAAGKVLDR NISEKIGDLQ AVMAVPDAET PTFCLHTDVS CRQRADVAIY 
       160        170        180        190        200
QDVYAVHAPT SLYHQAIKGV RVAYWIGFDT TPFMYNAMAG AYPSYSTNWA 
       210        220        230        240        250
DEQVLKAKNI GLCSTDLTEG RRGKLSIMRG KKMKPCDRVL FSVGSTLYPE 
       260        270        280        290        300
SRKLLKSWHL PSVFHLKGKL SFTCRCDTVV SCEGYVVKRI TISPGLYGKT 
       310        320        330        340        350
TGYAVTHHAD GFLMCKTTDT VDGERVSFSV CTYVPATICD QMTGILATEV 
       360        370        380        390        400
TPEDAQKLLV GLNQRIVVNG RTQRNTNTMK NYLLPVVAQA FSKWAKECRK 
       410        420        430        440        450
DMEDEKLLGI RERTLTCCCL WAFKKQKTHT VYKRPDTQSI QKVPAEFDSF 
       460        470        480        490        500
VVPSLWSSGL SIPLRTRIKW LLSKVPKTDL IPYSGDAKEA RDAEKEAEEE 
       510        520        530        540        550
REAELTREAL PPLQAAQDDV QVEIDVEQLE DRAGAGIIET PRGAIKVTAQ 
       560        570        580        590        600
PTDHVVGEYL VLSPQTVLRS QKLSLIHALA EQVKTCTHSG RAGRYAVEAY 
       610        620        630        640        650
DGRILVPSGY AISPEDFQSL SESATMVYNE REFVNRKLHH IALHGPALNT 
       660        670        680        690        700
DEESYELVRA ERTEHEYVYD VDQRRCCKKE EAAGLVLVGD LTNPPYHEFA 
       710        720        730        740        750
YEGLRIRPAC PYKTAVIGVF GVPGSGKSAI IKNLVTRQDL VTSGKKENCQ 
       760        770        780        790        800
EISTDVMRQR NLEISARTVD SLLLNGCNRP VDVLYVDEAF ACHSGTLLAL 
       810        820        830        840        850
IALVRPRQKV VLCGDPKQCG FFNMMQMKVN YNHNICTQVY HKSISRRCTL 
       860        870        880        890        900
PVTAIVSSLH YEGKMRTTNE YNKPIVVDTT GSTKPDPGDL VLTCFRGWVK 
       910        920        930        940        950
QLQIDYRGHE VMTAAASQGL TRKGVYAVRQ KVNENPLYAS TSEHVNVLLT 
       960        970        980        990       1000
RTEGKLVWKT LSGDPWIKTL QNPPKGNFKA TIKEWEVEHA SIMAGICNHQ 
      1010       1020       1030       1040       1050
VTFDTFQNKA NVCWAKSLVP ILETAGIKLN DRQWSQIIQA FKEDRAYSPE 
      1060       1070       1080       1090       1100
VALNEICTRM YGVDLDSGLF SKPLVSVHYA DNHWDNRPGG KMFGFNPEAA 
      1110       1120       1130       1140       1150
SILERKYPFT KGKWNTNKQI CVTTRRIEDF NPNTNIIPAN RRLPHSLVAE 
      1160       1170       1180       1190       1200
HRPVKGERME WLVNKINGHH VLLVSGYNLV LPTKRVTWVA PLGIRGADYT 
      1210       1220       1230       1240       1250
YNLELGLPAT LGRYDLVIIN IHTPFRIHHY QQCVDHAMKL QMLGGDSLRL 
      1260       1270       1280       1290       1300
LKPGGSLLIR AYGYADRTSE RVVCVLGRKF RSSRALKPPC VTSNTEMFFL 
      1310       1320       1330       1340       1350
FSNFDNGRRN FTTHVMNNQL NAAFVGQATR AGCAPSYRVK RMDIAKNDEE 
      1360       1370       1380       1390       1400
CVVNAANPRG LPGDGVCKAV YKKWPESFKN SATPVGTAKT VMCGTYPVIH 
      1410       1420       1430       1440       1450
AVGPNFSNYS ESEGDRELAA AYREVAKEVT RLGVNSVAIP LLSTGVYSGG 
      1460       1470       1480       1490       1500
KDRLTQSLNH LFTALDSTDA DVVIYCRDKE WEKKIAEAIQ MRTQVELLDE 
      1510       1520       1530       1540       1550
HISVDCDIIR VHPDSSLAGR KGYSTTEGSL YSYLEGTRFH QTAVDMAEVY 
      1560       1570       1580       1590       1600
TMWPKQTEAN EQVCLYALGE SIESIRQKCP VDDADASSPP KTVPCLCRYA 
      1610       1620       1630       1640       1650
MTPERVTRLR MNHVTSIIVC SSFPLPKYKI EGVQKVKCSK VMLFDHNVPS 
      1660       1670       1680       1690       1700
RVSPREYKSP QETAQEVSST TSLTHSQFDL SVDGEELPAP SDLEADAPIP 
      1710       1720       1730       1740       1750
EPTPDDRAVL TLPPTIDNFS AVSDWVMNTA PVAPPRRRRG KNLNVTCDER 
      1760       1770       1780       1790       1800
EGNVLPMASV RFFRADLHSI VQETAEIRDT AASLQAPLSV ATEPNQLPIS 
      1810       1820       1830       1840       1850
FGAPNETFPI TFGDFDEGEI ESLSSELLTF GDFSPGEVDD LTDSDWSTCS 
      1860       1870       1880       1890       1900
DTDDELXLDR AGGYIFSSDT GPGHLQQRSV RQTVLPVNTL EEVQEEKCYP 
      1910       1920       1930       1940       1950
PKLDEVKEQL LLKKLQESAS MANRSRYQSR KVENMKATIV QRLKGGCKLY 
      1960       1970       1980       1990       2000
LMSETPKVPT YRTTYPAPVY SPPINIRLSN PESAVAACNE FLARNYPTVA 
      2010       2020       2030       2040       2050
SYQITDEYDA YLDMVDGSES CLDRATFNPS KLRSYPKQHS YHAPTIRSAV 
      2060       2070       2080       2090       2100
PSPFQNTLQN VLAAATKRNC NVTQMRELPT LDSAVFNVEC FKKFACNQEY 
      2110       2120       2130       2140       2150
WKEFAASPIR ITTENLTTYV TKLKGPKAAA LFAKTHNLLP LQEVPMDRFT 
      2160       2170       2180       2190       2200
VDMKRDVKVT PGTKHTEERP KVQVIQAAEP LATAYLCGIH RELVRRLNAV 
      2210       2220       2230       2240       2250
LLPNVHTLFD MSAEDFDAII AAHFKPGDAV LETDIASFDK SQDDSLALTA 
      2260       2270       2280       2290       2300
LMLLEDLGVD HPLLDLIEAA FGEISSCHLP TGTRFKFGAM MKSGMFLTLF 
      2310       2320       2330       2340       2350
VNTLLNITIA SRVLEDRLTR SACAAFIGDD NIIHGVVSDE LMAARCATWM 
      2360       2370       2380       2390       2400
NMEVKIIDAV VSQKAPYFCG GFILYDTVAG TACRVADPLK RLFKLGKPLA 
      2410       2420       2430       2440       2450
AGDEQDDDRR RALADEVVRW QRTGLTDELE KAVHSRYEVQ GISVVVMSMA 
      2460       2470 
TFASSRSNFE KLRGPVVTLY GGPK
Length:2,474
Mass (Da):275,933
Last modified:November 23, 2004 - v1
Checksum:i0699DB0485FB3097
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY726732 Genomic RNA Translation: AAU43880.1

Keywords - Coding sequence diversityi

RNA suppression of termination

Similar proteinsi

Entry informationi

Entry nameiPOLN_CHIK3
AccessioniPrimary (citable) accession number: Q5XXP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: November 23, 2004
Last modified: April 25, 2018
This is version 97 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

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