Q8QZ73 (POLN_MAYAB) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 83. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 7 chains:
|Organism||Mayaro virus (strain Brazil) (MAYV) [Complete proteome]|
|Taxonomic identifier||374990 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Togaviridae › Alphavirus › SFV complex ›|
|Virus host||Aedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159]|
Haemagogus [TaxID: 7180]
Homo sapiens (Human) [TaxID: 9606]
|Sequence length||2436 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 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 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.
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).
P123 interacts with nsP4; nsP1, nsP2, nsP3 and nsP4 interact with each other, and with uncharacterized host factors By similarity.
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.
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 projection › host 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.
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.
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.
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.
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.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 2436||2436||Non-structural polyprotein||PRO_0000308393|
|Chain||1 – 1825||1825||P123'||PRO_0000229927|
|Chain||1 – 1819||1819||P123||PRO_0000229926|
|Chain||1 – 536||536||mRNA-capping enzyme nsP1||PRO_0000229928|
|Chain||537 – 1334||798||Protease nsP2||PRO_0000229929|
|Chain||1335 – 1825||491||Non-structural protein 3'||PRO_0000229931|
|Chain||1335 – 1819||485||Non-structural protein 3||PRO_0000229930|
|Chain||1826 – 2436||611||RNA-directed RNA polymerase nsP4||PRO_0000229932|
|Domain||691 – 843||153||(+)RNA virus helicase ATP-binding|
|Domain||844 – 992||149||(+)RNA virus helicase C-terminal|
|Domain||1005 – 1327||323||Peptidase C9|
|Domain||1335 – 1493||159||Macro|
|Domain||2190 – 2305||116||RdRp catalytic|
|Nucleotide binding||722 – 729||8||ATP Potential|
|Region||244 – 263||20||nsP1 membrane-binding By similarity|
|Region||1006 – 1025||20||Nucleolus localization signal By similarity|
|Motif||1182 – 1186||5||Nuclear localization signal By similarity|
|Active site||1014||1||For cysteine protease nsP2 activity By similarity|
|Active site||1084||1||For cysteine protease nsP2 activity By similarity|
|Site||536 – 537||2||Cleavage; by nsP2 By similarity|
|Site||1334 – 1335||2||Cleavage; by nsP2 By similarity|
|Site||1825 – 1826||2||Cleavage; by nsP2 By similarity|
Amino acid modifications
|Lipidation||417||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||419||1||S-palmitoyl cysteine; by host By similarity|
|AF237947 Genomic RNA. Translation: AAL79763.1.|
AF237947 Genomic RNA. Translation: AAL79765.1. Sequence problems.
|RefSeq||NP_579968.1. NC_003417.1. |
3D structure databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR027351. (+)RNA_virus_helicase_core_dom. |
|Pfam||PF01661. Macro. 1 hit. |
PF01707. Peptidase_C9. 1 hit.
PF00978. RdRP_2. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF01660. Vmethyltransf. 1 hit.
|SMART||SM00506. A1pp. 1 hit. |
|SUPFAM||SSF52540. SSF52540. 1 hit. |
|PROSITE||PS51154. MACRO. 1 hit. |
PS51520. NSP2PRO. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
|Accession||Primary (citable) accession number: Q8QZ73|
Secondary accession number(s): Q8QHM4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|