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Q8QZ73

- POLN_MAYAB

UniProt

Q8QZ73 - POLN_MAYAB

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Protein

Non-structural polyprotein

Gene
N/A
Organism
Mayaro virus (strain Brazil) (MAYV)
Status
Reviewed - Annotation score: 5 out of 5 - 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.
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 activityi

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).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei536 – 5372Cleavage; by nsP2 By similarity
Active sitei1014 – 10141For cysteine protease nsP2 activity By similarity
Active sitei1084 – 10841For cysteine protease nsP2 activity By similarity
Sitei1334 – 13352Cleavage; by nsP2 By similarity
Sitei1825 – 18262Cleavage; by nsP2 By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi722 – 7298ATP Reviewed prediction

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cysteine-type peptidase activity Source: UniProtKB-KW
  3. GTP binding Source: UniProtKB-KW
  4. helicase activity Source: UniProtKB-KW
  5. mRNA methyltransferase activity Source: InterPro
  6. polynucleotide 5'-phosphatase activity Source: UniProtKB-EC
  7. RNA binding Source: UniProtKB-KW
  8. RNA-directed RNA polymerase activity Source: UniProtKB-KW

GO - Biological processi

  1. 7-methylguanosine mRNA capping Source: UniProtKB-KW
  2. suppression by virus of host RNA polymerase II activity Source: UniProtKB-KW
  3. transcription, DNA-templated Source: InterPro
  4. viral RNA genome replication Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase, Methyltransferase, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase

Keywords - Biological processi

Eukaryotic 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

Keywords - Ligandi

ATP-binding, GTP-binding, Nucleotide-binding, RNA-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 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
OrganismiMayaro virus (strain Brazil) (MAYV)
Taxonomic identifieri374990 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageTogaviridaeAlphavirusSFV complex
Virus hostiAedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159]
Haemagogus [TaxID: 7180]
Homo sapiens (Human) [TaxID: 9606]
ProteomesiUP000007774: Genome

Subcellular locationi

Chain 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.
Chain 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.
Chain 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.
Chain 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.
Chain 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.

GO - Cellular componenti

  1. host cell endosome membrane Source: UniProtKB-SubCell
  2. host cell filopodium Source: UniProtKB-SubCell
  3. host cell lysosomal membrane Source: UniProtKB-SubCell
  4. host cell nucleus Source: UniProtKB-SubCell
  5. host cell plasma membrane Source: UniProtKB-SubCell
  6. membrane Source: UniProtKB-KW
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 24362436Non-structural polyproteinPRO_0000308393Add
BLAST
Chaini1 – 18251825P123'PRO_0000229927Add
BLAST
Chaini1 – 18191819P123PRO_0000229926Add
BLAST
Chaini1 – 536536mRNA-capping enzyme nsP1PRO_0000229928Add
BLAST
Chaini537 – 1334798Protease nsP2PRO_0000229929Add
BLAST
Chaini1335 – 1825491Non-structural protein 3'PRO_0000229931Add
BLAST
Chaini1335 – 1819485Non-structural protein 3PRO_0000229930Add
BLAST
Chaini1826 – 2436611RNA-directed RNA polymerase nsP4PRO_0000229932Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi417 – 4171S-palmitoyl cysteine; by host By similarity
Lipidationi419 – 4191S-palmitoyl cysteine; by host By similarity

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

Keywords - PTMi

Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PRIDEiQ8QZ73.

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 By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ8QZ73.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini691 – 843153(+)RNA virus helicase ATP-bindingAdd
BLAST
Domaini844 – 992149(+)RNA virus helicase C-terminalAdd
BLAST
Domaini1005 – 1327323Peptidase C9Add
BLAST
Domaini1335 – 1493159MacroAdd
BLAST
Domaini2190 – 2305116RdRp catalyticAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni244 – 26320nsP1 membrane-binding By similarityAdd
BLAST
Regioni1006 – 102520Nucleolus localization signal By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1182 – 11865Nuclear localization signal By similarity

Sequence similaritiesi

Contains 1 Macro domain.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027351. (+)RNA_virus_helicase_core_dom.
IPR002620. Alphavirus_nsp2pro.
IPR002589. Macro_dom.
IPR027417. P-loop_NTPase.
IPR007094. RNA-dir_pol_PSvirus.
IPR029063. SAM-dependent_MTases-like.
IPR002588. Tymovirus_MeTrfase.
IPR001788. Tymovirus_RNA-dep_RNA_pol.
[Graphical view]
PfamiPF01661. Macro. 1 hit.
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
[Graphical view]
SMARTiSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEiPS51154. MACRO. 1 hit.
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8QZ73-1 [UniParc]FASTAAdd to Basket

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MSKVFVDIEA ESPFLKSLQR AFPAFEVEAQ QVTPNDHANA RAFSHLATKL     50
IEQETEKDTL ILDIGSAPAR RMMSEHTYHC VCPMRSAEDP ERLLYYARKL 100
AKASGEVVDR NIAAKIDDLQ SVMATPDNES RTFCLHTDQT CRTQAEVAVY 150
QDVYAVHAPT SLYFQAMKGV RTAYWIGFDT TPFMFDTMAG AYPTYATNWA 200
DEQVLKARNI GLCSASLTEG HLGKLSIMRK KKMTPSDQIM FSVGSTLYIE 250
SRRLLKSWHL PSVFHLKGRQ SYTCRCDTIV SCEGYVVKKI TMSPGVFGKT 300
SGYAVTHHAE GFLVCKTTDT IAGERVSFPI CTYVPSTICD QMTGILATEV 350
TPEDAQKLLV GLNQRIVVNG RTQRNTNTMK NYLLPVVSQA FSKWAKEYRL 400
DQEDEKNMGM RERTLTCCCL WAFKTHKNHT MYKKPDTQTI VKVPSEFNSF 450
VIPSLWSAGL SIGIRHRIRL LLQSRRVEPL VPSMDVGEAR AAEREAAEAK 500
EAEDTLAALP PLIPTAPVLD DIPEVDVEEL EFRAGAGVVE TPRNALKVTP 550
QDRDTMVGSY LVLSPQTVLK SVKLQALHPL AESVKIITHK GRAGRYQVDA 600
YDGRVLLPTG AAIPVPDFQA LSESATMVYN EREFINRKLY HIAVHGAALN 650
TDEEGYEKVR AESTDAEYVY DVDRKQCVKR EEAEGLVMIG DLINPPFHEF 700
AYEGLKRRPA APYKTTVVGV FGVPGSGKSG IIKSLVTRGD LVASGKKENC 750
QEIMLDVKRY RDLDMTAKTV DSVLLNGVKQ TVDVLYVDEA FACHAGTLLA 800
LIATVRPRKK VVLCGDPKQC GFFNLMQLQV NFNHNICTEV DHKSISRRCT 850
LPITAIVSTL HYEGRMRTTN PYNKPVIIDT TGQTKPNRED IVLTCFRGWV 900
KQLQLDYRGH EVMTAAASQG LTRKGVYAVR MKVNENPLYA QSSEHVNVLL 950
TRTEGRLVWK TLSGDPWIKT LSNIPKGNFT ATLEDWQREH DTIMRAITQE 1000
AAPLDVFQNK AKVCWAKCLV PVLETAGIKL SATDWSAIIL AFKEDRAYSP 1050
EVALNEICTK IYGVDLDSGL FSAPRVSLHY TTNHWDNSPG GRMYGFSVEA 1100
ANRLEQQHPF YRGRWASGQV LVAERKTQPI DVTCNLIPFN RRLPHTLVTE 1150
YHPIKGERVE WLVNKIPGYH VLLVSEYNLI LPRRKVTWIA PPTVTGADLT 1200
YDLDLGLPPN AGRYDLVFVN MHTPYRLHHY QQCVDHAMKL QMLGGDALYL 1250
LKPGGSLLLS TYAYADRTSE AVVTALARRF SSFRAVTVRC VTSNTEVFLL 1300
FTNFDNGRRT VTLHQTNGKL SSIYAGTVLQ AAGCAPAYAV KRADIATAIE 1350
DAVVNAANHR GQVGDGVCRA VARKWPQAFR NAATPVGTAK TVKCDETYII 1400
HAVGPNFNNT SEAEGDRDLA AAYRAVAAEI NRLSISSVAI PLLSTGIFSA 1450
GKDRVHQSLS HLLAAMDTTE ARVTIYCRDK TWEQKIKTVL QNRSATELVS 1500
DELQFEVNLT RVHPDSSLVG RPGYSTTDGT LYSYMEGTKF HQAALDMAEI 1550
TTLWPRVQDA NEHICLYALG ETMDNIRARC PVEDSDSSTP PKTVPCLCRY 1600
AMTPERVTRL RMHHTKDFVV CSSFQLPKYR IPGVQRVKCE KVMLFDAAPP 1650
ASVSPVQYLT NQSETTISLS SFSITSDSSS LSTFPDLESA EELDHDSQSV 1700
RPALNEPDDH QPTPTAELAT HPVPPPRPNR ARRLAAARVQ VQVEVHQPPS 1750
NQPTKPIPAP RTSLRPVPAP RRYVPRPVVE LPWPLETIDV EFGAPTEEES 1800
DITFGDFSAS EWETISNSSL GRAGAYIFSS DVGPGHLQQK SVRQHDLEVP 1850
IMDRVIEEKV YPPKLDEAKE KQLLLKLQMH ATDANRSRYQ SRKVENMKAT 1900
IIDRLKQGSA YYVSAAADKA VTYHVRYAKP RYSVPVMQRL SSATIAVATC 1950
NEFLARNYPT VASYQITDEY DAYLDMVDGS ESCLDRANFC PAKLRCYPKH 2000
HAYHMPQIRS AVPSPFQNTL QNVLAAATKR NCNVTQMREL PTLDSAVYNV 2050
ECFRKYACNN EYWEEFAKKP IRITTENLTT YVTKLKGGKA AALFAKTHNL 2100
VPLQEVPMDR FIMDMKRDVK VTPGTKHTEE RPKVQVIQAA EPLATAYLCG 2150
IHRELVRRLN AVLLPNIHTL FDMSAEDFDA IISEHFKPGD HVLETDIASF 2200
DKSQDDSLAL TGLMILEDLG VDNQLLDLIE AAFGQITSCH LPTGTRFKFG 2250
AMMKSGMFLT LFINTVLNIT IASRVLEARL TNSACAAFIG DDNVVHGVVS 2300
DKLMADRCAT WVNMEVKIID AVMCIKPPYF CGGFLVYDHV TRTACRIADP 2350
LKRLFKLGKP LPADDCQDED RRRALYDEVK KWSRSGLGSE IEVALASRYR 2400
LEGSYNLLLA MSTFAHSMKN FSALRGPVIH LYGGPK 2436
Length:2,436
Mass (Da):271,885
Last modified:April 4, 2006 - v2
Checksum:iBFF43A0DC04D3C59
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF237947 Genomic RNA. Translation: AAL79763.1.
AF237947 Genomic RNA. Translation: AAL79765.1. Sequence problems.
RefSeqiNP_579968.1. NC_003417.1.
NP_579969.1. NC_003417.1.

Genome annotation databases

GeneIDi935140.
935142.

Keywords - Coding sequence diversityi

RNA suppression of termination

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF237947 Genomic RNA. Translation: AAL79763.1 .
AF237947 Genomic RNA. Translation: AAL79765.1 . Sequence problems.
RefSeqi NP_579968.1. NC_003417.1.
NP_579969.1. NC_003417.1.

3D structure databases

ProteinModelPortali Q8QZ73.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi Q8QZ73.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 935140.
935142.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR027351. (+)RNA_virus_helicase_core_dom.
IPR002620. Alphavirus_nsp2pro.
IPR002589. Macro_dom.
IPR027417. P-loop_NTPase.
IPR007094. RNA-dir_pol_PSvirus.
IPR029063. SAM-dependent_MTases-like.
IPR002588. Tymovirus_MeTrfase.
IPR001788. Tymovirus_RNA-dep_RNA_pol.
[Graphical view ]
Pfami PF01661. Macro. 1 hit.
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
[Graphical view ]
SMARTi SM00506. A1pp. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 1 hit.
PROSITEi PS51154. MACRO. 1 hit.
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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].

Entry informationi

Entry nameiPOLN_MAYAB
AccessioniPrimary (citable) accession number: Q8QZ73
Secondary accession number(s): Q8QHM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: July 9, 2014
This is version 88 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Multifunctional enzyme

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi