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Q8QZ73 (POLN_MAYAB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-structural polyprotein
Alternative name(s):
Polyprotein nsP1234
Short name=P1234

Cleaved into the following 7 chains:

  1. P123
  2. P123'
  3. mRNA-capping enzyme nsP1
    EC=2.1.1.-
    EC=2.7.7.-
    Alternative name(s):
    Non-structural protein 1
  4. 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
  5. Non-structural protein 3
    Short name=nsP3
  6. Non-structural protein 3'
    Short name=nsP3'
  7. RNA-directed RNA polymerase nsP4
    EC=2.7.7.48
    Alternative name(s):
    Non-structural protein 4
    Short name=nsP4
OrganismMayaro virus (strain Brazil) (MAYV) [Complete proteome]
Taxonomic identifier374990 [NCBI]
Taxonomic lineageVirusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirusSFV complex
Virus hostAedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159]
Haemagogus [TaxID: 7180]
Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length2436 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

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.

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.

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.

Catalytic activity

S-adenosyl-L-methionine + GTP = m7GTP.

m7GTP + (5')pp-Pur-mRNA = diphosphate + m7G(5')ppp-Pur-mRNA.

(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).

Subunit structure

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: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host 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.

P123: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity.

P123': Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity.

mRNA-capping enzyme nsP1: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host cell projectionhost filopodium 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 and its filopodial extensions By similarity.

Protease nsP2: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host 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.

Non-structural protein 3: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host 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.

Non-structural protein 3': Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host 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.

RNA-directed RNA polymerase nsP4: Host endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity.

Induction

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.

Post-translational modification

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.

nsP1 is palmitoylated by host By similarity.

nsP4 is ubiquitinated; targets the protein for rapid degradation via the ubiquitin system By similarity.

Miscellaneous

The genome codes for P123, but readthrough of a terminator codon UGA occurs between the codons for Ser-1819 and Leu-1820. 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.

Sequence similarities

Contains 1 (+)RNA virus helicase ATP-binding domain.

Contains 1 (+)RNA virus helicase C-terminal domain.

Contains 1 Macro domain.

Contains 1 peptidase C9 domain.

Contains 1 RdRp catalytic domain.

Ontologies

Keywords
   Biological processHost gene expression shutoff by virus
Host transcription shutoff by virus
Host-virus interaction
Inhibition of host RNA polymerase II by virus
mRNA capping
mRNA processing
Viral RNA replication
   Cellular componentHost cell membrane
Host cell projection
Host cytoplasm
Host endosome
Host lysosome
Host membrane
Host nucleus
Membrane
   Coding sequence diversityRNA suppression of termination
   LigandATP-binding
GTP-binding
Nucleotide-binding
RNA-binding
   Molecular functionHelicase
Hydrolase
Methyltransferase
Nucleotidyltransferase
Protease
RNA-directed RNA polymerase
Thiol protease
Transferase
   PTMLipoprotein
Palmitate
Ubl conjugation
   Technical termComplete proteome
Multifunctional enzyme
Gene Ontology (GO)
   Biological_process7-methylguanosine mRNA capping

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host RNA polymerase II activity

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: InterPro

viral RNA genome replication

Inferred from electronic annotation. Source: InterPro

   Cellular_componenthost cell endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell filopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA-directed RNA polymerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

cysteine-type peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

helicase activity

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA methyltransferase activity

Inferred from electronic annotation. Source: InterPro

polynucleotide 5'-phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 24362436Non-structural polyprotein
PRO_0000308393
Chain1 – 18251825P123'
PRO_0000229927
Chain1 – 18191819P123
PRO_0000229926
Chain1 – 536536mRNA-capping enzyme nsP1
PRO_0000229928
Chain537 – 1334798Protease nsP2
PRO_0000229929
Chain1335 – 1825491Non-structural protein 3'
PRO_0000229931
Chain1335 – 1819485Non-structural protein 3
PRO_0000229930
Chain1826 – 2436611RNA-directed RNA polymerase nsP4
PRO_0000229932

Regions

Domain691 – 843153(+)RNA virus helicase ATP-binding
Domain844 – 992149(+)RNA virus helicase C-terminal
Domain1005 – 1327323Peptidase C9
Domain1335 – 1493159Macro
Domain2190 – 2305116RdRp catalytic
Nucleotide binding722 – 7298ATP Potential
Region244 – 26320nsP1 membrane-binding By similarity
Region1006 – 102520Nucleolus localization signal By similarity
Motif1182 – 11865Nuclear localization signal By similarity

Sites

Active site10141For cysteine protease nsP2 activity By similarity
Active site10841For cysteine protease nsP2 activity By similarity
Site536 – 5372Cleavage; by nsP2 By similarity
Site1334 – 13352Cleavage; by nsP2 By similarity
Site1825 – 18262Cleavage; by nsP2 By similarity

Amino acid modifications

Lipidation4171S-palmitoyl cysteine; by host By similarity
Lipidation4191S-palmitoyl cysteine; by host By similarity

Sequences

Sequence LengthMass (Da)Tools
Q8QZ73 [UniParc].

Last modified April 4, 2006. Version 2.
Checksum: BFF43A0DC04D3C59

FASTA2,436271,885
        10         20         30         40         50         60 
MSKVFVDIEA ESPFLKSLQR AFPAFEVEAQ QVTPNDHANA RAFSHLATKL IEQETEKDTL 

        70         80         90        100        110        120 
ILDIGSAPAR RMMSEHTYHC VCPMRSAEDP ERLLYYARKL AKASGEVVDR NIAAKIDDLQ 

       130        140        150        160        170        180 
SVMATPDNES RTFCLHTDQT CRTQAEVAVY QDVYAVHAPT SLYFQAMKGV RTAYWIGFDT 

       190        200        210        220        230        240 
TPFMFDTMAG AYPTYATNWA DEQVLKARNI GLCSASLTEG HLGKLSIMRK KKMTPSDQIM 

       250        260        270        280        290        300 
FSVGSTLYIE SRRLLKSWHL PSVFHLKGRQ SYTCRCDTIV SCEGYVVKKI TMSPGVFGKT 

       310        320        330        340        350        360 
SGYAVTHHAE GFLVCKTTDT IAGERVSFPI CTYVPSTICD QMTGILATEV TPEDAQKLLV 

       370        380        390        400        410        420 
GLNQRIVVNG RTQRNTNTMK NYLLPVVSQA FSKWAKEYRL DQEDEKNMGM RERTLTCCCL 

       430        440        450        460        470        480 
WAFKTHKNHT MYKKPDTQTI VKVPSEFNSF VIPSLWSAGL SIGIRHRIRL LLQSRRVEPL 

       490        500        510        520        530        540 
VPSMDVGEAR AAEREAAEAK EAEDTLAALP PLIPTAPVLD DIPEVDVEEL EFRAGAGVVE 

       550        560        570        580        590        600 
TPRNALKVTP QDRDTMVGSY LVLSPQTVLK SVKLQALHPL AESVKIITHK GRAGRYQVDA 

       610        620        630        640        650        660 
YDGRVLLPTG AAIPVPDFQA LSESATMVYN EREFINRKLY HIAVHGAALN TDEEGYEKVR 

       670        680        690        700        710        720 
AESTDAEYVY DVDRKQCVKR EEAEGLVMIG DLINPPFHEF AYEGLKRRPA APYKTTVVGV 

       730        740        750        760        770        780 
FGVPGSGKSG IIKSLVTRGD LVASGKKENC QEIMLDVKRY RDLDMTAKTV DSVLLNGVKQ 

       790        800        810        820        830        840 
TVDVLYVDEA FACHAGTLLA LIATVRPRKK VVLCGDPKQC GFFNLMQLQV NFNHNICTEV 

       850        860        870        880        890        900 
DHKSISRRCT LPITAIVSTL HYEGRMRTTN PYNKPVIIDT TGQTKPNRED IVLTCFRGWV 

       910        920        930        940        950        960 
KQLQLDYRGH EVMTAAASQG LTRKGVYAVR MKVNENPLYA QSSEHVNVLL TRTEGRLVWK 

       970        980        990       1000       1010       1020 
TLSGDPWIKT LSNIPKGNFT ATLEDWQREH DTIMRAITQE AAPLDVFQNK AKVCWAKCLV 

      1030       1040       1050       1060       1070       1080 
PVLETAGIKL SATDWSAIIL AFKEDRAYSP EVALNEICTK IYGVDLDSGL FSAPRVSLHY 

      1090       1100       1110       1120       1130       1140 
TTNHWDNSPG GRMYGFSVEA ANRLEQQHPF YRGRWASGQV LVAERKTQPI DVTCNLIPFN 

      1150       1160       1170       1180       1190       1200 
RRLPHTLVTE YHPIKGERVE WLVNKIPGYH VLLVSEYNLI LPRRKVTWIA PPTVTGADLT 

      1210       1220       1230       1240       1250       1260 
YDLDLGLPPN AGRYDLVFVN MHTPYRLHHY QQCVDHAMKL QMLGGDALYL LKPGGSLLLS 

      1270       1280       1290       1300       1310       1320 
TYAYADRTSE AVVTALARRF SSFRAVTVRC VTSNTEVFLL FTNFDNGRRT VTLHQTNGKL 

      1330       1340       1350       1360       1370       1380 
SSIYAGTVLQ AAGCAPAYAV KRADIATAIE DAVVNAANHR GQVGDGVCRA VARKWPQAFR 

      1390       1400       1410       1420       1430       1440 
NAATPVGTAK TVKCDETYII HAVGPNFNNT SEAEGDRDLA AAYRAVAAEI NRLSISSVAI 

      1450       1460       1470       1480       1490       1500 
PLLSTGIFSA GKDRVHQSLS HLLAAMDTTE ARVTIYCRDK TWEQKIKTVL QNRSATELVS 

      1510       1520       1530       1540       1550       1560 
DELQFEVNLT RVHPDSSLVG RPGYSTTDGT LYSYMEGTKF HQAALDMAEI TTLWPRVQDA 

      1570       1580       1590       1600       1610       1620 
NEHICLYALG ETMDNIRARC PVEDSDSSTP PKTVPCLCRY AMTPERVTRL RMHHTKDFVV 

      1630       1640       1650       1660       1670       1680 
CSSFQLPKYR IPGVQRVKCE KVMLFDAAPP ASVSPVQYLT NQSETTISLS SFSITSDSSS 

      1690       1700       1710       1720       1730       1740 
LSTFPDLESA EELDHDSQSV RPALNEPDDH QPTPTAELAT HPVPPPRPNR ARRLAAARVQ 

      1750       1760       1770       1780       1790       1800 
VQVEVHQPPS NQPTKPIPAP RTSLRPVPAP RRYVPRPVVE LPWPLETIDV EFGAPTEEES 

      1810       1820       1830       1840       1850       1860 
DITFGDFSAS EWETISNSSL GRAGAYIFSS DVGPGHLQQK SVRQHDLEVP IMDRVIEEKV 

      1870       1880       1890       1900       1910       1920 
YPPKLDEAKE KQLLLKLQMH ATDANRSRYQ SRKVENMKAT IIDRLKQGSA YYVSAAADKA 

      1930       1940       1950       1960       1970       1980 
VTYHVRYAKP RYSVPVMQRL SSATIAVATC NEFLARNYPT VASYQITDEY DAYLDMVDGS 

      1990       2000       2010       2020       2030       2040 
ESCLDRANFC PAKLRCYPKH HAYHMPQIRS AVPSPFQNTL QNVLAAATKR NCNVTQMREL 

      2050       2060       2070       2080       2090       2100 
PTLDSAVYNV ECFRKYACNN EYWEEFAKKP IRITTENLTT YVTKLKGGKA AALFAKTHNL 

      2110       2120       2130       2140       2150       2160 
VPLQEVPMDR FIMDMKRDVK VTPGTKHTEE RPKVQVIQAA EPLATAYLCG IHRELVRRLN 

      2170       2180       2190       2200       2210       2220 
AVLLPNIHTL FDMSAEDFDA IISEHFKPGD HVLETDIASF DKSQDDSLAL TGLMILEDLG 

      2230       2240       2250       2260       2270       2280 
VDNQLLDLIE AAFGQITSCH LPTGTRFKFG AMMKSGMFLT LFINTVLNIT IASRVLEARL 

      2290       2300       2310       2320       2330       2340 
TNSACAAFIG DDNVVHGVVS DKLMADRCAT WVNMEVKIID AVMCIKPPYF CGGFLVYDHV 

      2350       2360       2370       2380       2390       2400 
TRTACRIADP LKRLFKLGKP LPADDCQDED RRRALYDEVK KWSRSGLGSE IEVALASRYR 

      2410       2420       2430 
LEGSYNLLLA MSTFAHSMKN FSALRGPVIH LYGGPK 

« Hide

References

[1]Netto M.C.M.G., Shirako Y., Strauss E.G., Carvalho M.G.C., Strauss J.H.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF237947 Genomic RNA. Translation: AAL79763.1.
AF237947 Genomic RNA. Translation: AAL79765.1. Sequence problems.
RefSeqNP_579968.1. NC_003417.1.
NP_579969.1. NC_003417.1.

3D structure databases

ProteinModelPortalQ8QZ73.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ8QZ73.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID935140.
935142.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027351. (+)RNA_virus_helicase_core_dom.
IPR002620. Alphavirus_nsp2pro.
IPR002589. Macro_dom.
IPR027417. P-loop_NTPase.
IPR007094. RNA-dir_pol_PSvirus.
IPR002588. Tymovirus_MeTrfase.
IPR001788. Tymovirus_RNA-dep_RNA_pol.
[Graphical view]
PfamPF01661. Macro. 1 hit.
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
[Graphical view]
SMARTSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS51154. MACRO. 1 hit.
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePOLN_MAYAB
AccessionPrimary (citable) accession number: Q8QZ73
Secondary accession number(s): Q8QHM4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: April 16, 2014
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries