Results | viHumans

UniProt ID

Q8QZ73

Status

Reviewed

Host

Aedes Aegypti (Yellowfever Mosquito) (Culex Aegypti) [TaxID: 7159]; Haemagogus [TaxID: 7180]; Homo Sapiens (Human) [TaxID: 9606]

Gene Name

Not Available

Protein Name

♦Non-structural polyprotein (Polyprotein nsP1234) (P1234) [Cleaved into: P123
♦ P123'
♦ mRNA-capping enzyme nsP1 (EC 2.1.1.-) (EC 2.7.7.-) (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) (Non-structural protein 2) (nsP2)
♦ Non-structural protein 3 (nsP3)
♦ Non-structural protein 3' (nsP3')
♦ RNA-directed RNA polymerase nsP4 (EC 2.7.7.48) (Non-structural protein 4) (nsP4)]

Organism Name

Mayaro Virus (strain Brazil) (MAYV)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Togaviridae> Alphavirus (arboviruses Group A)> Mayaro Virus> Mayaro Virus (strain Brazil) (MAYV)

RefSeq

NC_003417.1 ; AF237947.1

PubMed ID

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

vg:935140;vg:935142

Reactome

Not Available

Sequence

							MSKVFVDIEAESPFLKSLQRAFPAFEVEAQQVTPNDHANARAFSHLATKLIEQETEKDTLILDIGSAPARRMMSEHTYHCVCPMRSAEDPERLLYYARKL
AKASGEVVDRNIAAKIDDLQSVMATPDNESRTFCLHTDQTCRTQAEVAVYQDVYAVHAPTSLYFQAMKGVRTAYWIGFDTTPFMFDTMAGAYPTYATNWA
DEQVLKARNIGLCSASLTEGHLGKLSIMRKKKMTPSDQIMFSVGSTLYIESRRLLKSWHLPSVFHLKGRQSYTCRCDTIVSCEGYVVKKITMSPGVFGKT
SGYAVTHHAEGFLVCKTTDTIAGERVSFPICTYVPSTICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPVVSQAFSKWAKEYRL
DQEDEKNMGMRERTLTCCCLWAFKTHKNHTMYKKPDTQTIVKVPSEFNSFVIPSLWSAGLSIGIRHRIRLLLQSRRVEPLVPSMDVGEARAAEREAAEAK
EAEDTLAALPPLIPTAPVLDDIPEVDVEELEFRAGAGVVETPRNALKVTPQDRDTMVGSYLVLSPQTVLKSVKLQALHPLAESVKIITHKGRAGRYQVDA
YDGRVLLPTGAAIPVPDFQALSESATMVYNEREFINRKLYHIAVHGAALNTDEEGYEKVRAESTDAEYVYDVDRKQCVKREEAEGLVMIGDLINPPFHEF
AYEGLKRRPAAPYKTTVVGVFGVPGSGKSGIIKSLVTRGDLVASGKKENCQEIMLDVKRYRDLDMTAKTVDSVLLNGVKQTVDVLYVDEAFACHAGTLLA
LIATVRPRKKVVLCGDPKQCGFFNLMQLQVNFNHNICTEVDHKSISRRCTLPITAIVSTLHYEGRMRTTNPYNKPVIIDTTGQTKPNREDIVLTCFRGWV
KQLQLDYRGHEVMTAAASQGLTRKGVYAVRMKVNENPLYAQSSEHVNVLLTRTEGRLVWKTLSGDPWIKTLSNIPKGNFTATLEDWQREHDTIMRAITQE
AAPLDVFQNKAKVCWAKCLVPVLETAGIKLSATDWSAIILAFKEDRAYSPEVALNEICTKIYGVDLDSGLFSAPRVSLHYTTNHWDNSPGGRMYGFSVEA
ANRLEQQHPFYRGRWASGQVLVAERKTQPIDVTCNLIPFNRRLPHTLVTEYHPIKGERVEWLVNKIPGYHVLLVSEYNLILPRRKVTWIAPPTVTGADLT
YDLDLGLPPNAGRYDLVFVNMHTPYRLHHYQQCVDHAMKLQMLGGDALYLLKPGGSLLLSTYAYADRTSEAVVTALARRFSSFRAVTVRCVTSNTEVFLL
FTNFDNGRRTVTLHQTNGKLSSIYAGTVLQAAGCAPAYAVKRADIATAIEDAVVNAANHRGQVGDGVCRAVARKWPQAFRNAATPVGTAKTVKCDETYII
HAVGPNFNNTSEAEGDRDLAAAYRAVAAEINRLSISSVAIPLLSTGIFSAGKDRVHQSLSHLLAAMDTTEARVTIYCRDKTWEQKIKTVLQNRSATELVS
DELQFEVNLTRVHPDSSLVGRPGYSTTDGTLYSYMEGTKFHQAALDMAEITTLWPRVQDANEHICLYALGETMDNIRARCPVEDSDSSTPPKTVPCLCRY
AMTPERVTRLRMHHTKDFVVCSSFQLPKYRIPGVQRVKCEKVMLFDAAPPASVSPVQYLTNQSETTISLSSFSITSDSSSLSTFPDLESAEELDHDSQSV
RPALNEPDDHQPTPTAELATHPVPPPRPNRARRLAAARVQVQVEVHQPPSNQPTKPIPAPRTSLRPVPAPRRYVPRPVVELPWPLETIDVEFGAPTEEES
DITFGDFSASEWETISNSSLGRAGAYIFSSDVGPGHLQQKSVRQHDLEVPIMDRVIEEKVYPPKLDEAKEKQLLLKLQMHATDANRSRYQSRKVENMKAT
IIDRLKQGSAYYVSAAADKAVTYHVRYAKPRYSVPVMQRLSSATIAVATCNEFLARNYPTVASYQITDEYDAYLDMVDGSESCLDRANFCPAKLRCYPKH
HAYHMPQIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTLDSAVYNVECFRKYACNNEYWEEFAKKPIRITTENLTTYVTKLKGGKAAALFAKTHNL
VPLQEVPMDRFIMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNIHTLFDMSAEDFDAIISEHFKPGDHVLETDIASF
DKSQDDSLALTGLMILEDLGVDNQLLDLIEAAFGQITSCHLPTGTRFKFGAMMKSGMFLTLFINTVLNITIASRVLEARLTNSACAAFIGDDNVVHGVVS
DKLMADRCATWVNMEVKIIDAVMCIKPPYFCGGFLVYDHVTRTACRIADPLKRLFKLGKPLPADDCQDEDRRRALYDEVKKWSRSGLGSEIEVALASRYR
LEGSYNLLLAMSTFAHSMKNFSALRGPVIHLYGGPK
						

Length

2436

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

04-04-2006

Protein Existence

Evidence at protein level

Amino Acid composition

Amino Acid	Count	% Frequency	Amino Acid	Count	% Frequency
Alanine (A)			Leucine (L)
Arginine (R)			Lysine (K)
Asparagine (N)			Methionine (M)
Aspartic Acid (D)			Phenylalanine (F)
Cysteine (C)			Proline (P)
Glutamine (Q)			Serine (S)
Glutamic Acid (E)			Threonine (T)
Glycine (G)			Tryptophan (W)
Histidine (H)			Tyrosine (Y)
Isoleucine (I)			Valine (V)

Sum of Absolute Deviation from Amino Acid Occurrence Frequencies

Aliphatic Index

Instability Index

Secondary Structure features

% Number of Residues in Helices	% Number of Residues in Strands	% Number of Residues in Coils

Structural Difficulty(SD) index

Role(s)

♦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.
♦ 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).

EC

2.1.1.- , 2.7.7.- , 3.1.3.33 , 3.4.22.- , 3.6.1.15 , 3.6.4.13 , 2.7.7.48

Experimentally known GO terms

GO:0003723 ;   GO:0003968 ;   GO:0004386 ;   GO:0004651 ;   GO:0005524 ;
GO:0005525 ;   GO:0006351 ;   GO:0006370 ;   GO:0008174 ;   GO:0008234 ;
GO:0016020 ;   GO:0020002 ;   GO:0039523 ;   GO:0039694 ;   GO:0042025 ;
GO:0044175 ;   GO:0044176 ;   GO:0044188

Subcellular Location

♦ Non-structural polyprotein: Host endosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . 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 . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side .
♦ P123': Host endosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side .
♦ mRNA-capping enzyme nsP1: Host endosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host cell membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host cell projection, host filopodium . 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 . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host nucleus . 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 . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host cytoplasm . 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 . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side . Host cytoplasm . 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 . Host lysosome membrane
♦ Peripheral membrane protein
♦ Cytoplasmic side .

Domain(s)

♦DOMAIN 28 259 Alphavirus-like MT.
♦ DOMAIN 691 843 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 844 992 (+)RNA virus helicase C-terminal.
♦ DOMAIN 1005 1327 Peptidase C9.
♦ DOMAIN 1335 1493 Macro.
♦ DOMAIN 2190 2305 RdRp catalytic.

Motif(s)

MOTIF 1182 1186 Nuclear localization signal.

Methods of 3D structure generation

NMR spectroscopy (1)

Experimetally known structure

5IQ5

Active Site(s)

♦ACT_SITE 1014 1014 For cysteine protease nsP2 activity.
♦ ACT_SITE 1084 1084 For cysteine protease nsP2 activity.

Predicted 3D Structures

Protein couldn't be modeled using I-Tasser and Raptor X because of length constraints of the software.

Experimentally known Ligand(s)

Not Available

Virtually Screened Ligands

Virtual screening has been performed using RASPD

						Million Molecules

					
Best 20 Hit molecules 
Not Available