Results | viHumans

UniProt ID

Q306W8

Status

Reviewed

Host

Aedes [TaxID: 7158]; Homo Sapiens (Human) [TaxID: 9606]; Passeriformes [TaxID: 9126]

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

Eastern Equine Encephalitis Virus (strain PE-3.0815) (EEEV) (Eastern Equine Encephalomyelitis Virus)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Togaviridae> Alphavirus (arboviruses Group A)> Eastern Equine Encephalitis Virus (EEEV) (Eastern Equine Encephalomyelitis Virus)> Eastern Equine Encephalitis Virus (strain PE-3.0815) (EEEV) (Eastern Equine Encephalomyelitis Virus)

RefSeq

NC_003899.1 ; X63135.1

PubMed ID

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MEKVHVDLDADSPYVKLLQKCFPHFEIEATQVTDNDHANARAFSHLATKLIESEVDPDQVILDIGSAPVRHTHSKHKYHCICPMISAEDPDRLQRYADKL
RKSDVTDRFIASKAADLLTVMSTPDVETPSLCMHTDSTCRYHGTVAVYQDVYAVHAPTSIYHQALKGVRTIYWIGFDTTPFMYKNMAGAYPTYNTNWADE
SVLEARNIGLCSSDLHEKRLGKISIMRKKKLQPTNKVVFSVGSTIYTEERILLRSWHLPNVFHLKGKTSFTGRCNTIVSCDGYVVKKITISPGIYGKVDN
LASTLHREGFLSCKVTDTLRGERVSFPVCTYVPATLCDQMTGILATDVSVDDAQKLLVGLNQRIVVNGRTQRNTNTMQNYLLPVVAQAFSRWAREYRADL
EDEKDLGVRERSLVMGCCWAFKTHKITSIYKKPGTQTIKKVPAVFNSFVIPQFNSYGLNIGLRRRIKMLLEEKRKPAPIITEADVAHLKGMQEEAEAVAE
AEAVRAALPPLLPEVERETIEADIDLIMQEAGAGSVETPRRHIKVTTYPGEETIGSYAVLSPQAVLNSEKLACIHPLAEQVLVMTHKGRAGRYKVEPYHG
RVVVPSGTAIPIPDFQALSESATIVYNEREFVNRYLHHIAINGGAINTDEEYYKVLRSSEADSEYVFDIDARKCVKKADAGPMCLVGELVDPPFHEFAYE
SLKTRPAAPHKVPTIGVYGVPGSGKSGIIKSAVTKRDLVVSAKKENCTEIIKDVKRMRGMDIAARTVDSVLLNGVKHPVDTLYIDEAFACHAGTLLALIA
IVKPKKVVLCGDPKQCGFFNMMCLKVHFNHEICTEVYHKSISRRCTKTVTAIVSTLFYDKRMRTVNPCSDKIIIDTTSTTKPQRDDIILTCFRGWVKQLQ
IDYKNHEIMTAAASQGLTRKGVYAVRYKVNENPLYAQTSEHVNVLLTRTEKRIVWKTLAGDPWIKTLTAHYPGEFSATLEEWQAEHDAIMERILETPASS
DVYQNKVHVCWAKALEPVLATANITLTRSQWETIPAFKDDKAFSPEMALNFLCTRFFGVDIDSGLFSAPTVPLTYTNEHWDNSPGPNRYGLCMRTAKELA
RRYPCILKAVDTGRLADVRTNTIKDYSPLINVVPLNRRLPHSLVVSHRYTGDGNYSQLLSKLIGKTVLVIGTPISVPGKRVETLGPGPQCTYKADLDLGI
PSTIGKYDIIFVNVRTPYKHHHYQQCEDHAIHHSMLTRKAVDHLNKGGTCVALGYGTADRATENIISAVARSFRFSRVCQPKCAWENTEVAFVFFGKDNG
NHLRDQDQLSIVLNNIYQGSTQYEAGRAPAYRVIRGDISKSTDEAIVNAANNKGQPGAGVCGALYKKWPGAFDKVPIATGTAHLVKHTPNIIHAVGPNFS
RVSEVEGNQKLSEVYMDIAKIINRERYNKVSIPLLSTGIYAGGKDRVMQSLNHLFTAMDTTDADVTIYCLDKQWEARIKDAIARKESVEELVEDDKPVDI
ELVRVHPLSSLVGRPGYSTDEGKVHSYLEGTRFHQTAKDIAEIYAMWPNKQEANEQICLYVLGESMTSIRSKCPVEDSEASSPPHTIPCLCNYAMTAERV
YRLRMAKNEQFAVCSSFQLPKYRITGVQKIQCNKPVIFSGVVPPAIHPRKFSAIEETVPVTIERLVPRRPAPPVPVPARIPSPRCSPAVSMQSLGGSSTS
DVVISEAEVHDSDSDCSIPPMPFVVEAEVHASQGSHWSIPSASGFEIRELPEDRSISGSPTRTSVISDHSVNLITFDSVTDIFENFKQAPFQFLSEIRPI
PAPRRRVGGFETDTKRYDKTEEKPIPKPRTRTTKYKQPPGVARSISEAELDEFIRRHSNRYEAGAYIFSSETGQGHLQQKSTRQCKLQNPILERSVHEKF
YAPRLDLEREKLLQKKLQLCASEGNRSRYQSRKVENMKAITAERLLQGIGAYLSAESQPVECYKVNYPVPIYSTTRSNRFSSADVAVRVCNLVLQENFPT
VASYTITDEYDAYLDMVDGASCCLDTATFCPAKLRSFPKKHSYLRPEIRSAVPSPIQNTLQNVLAAATKRNCNVTQMRELPVLDSAAFNVECFKKYACND
EYWDTFKNNPIRLTTENVTQYVTKLKGPKAAALFAKTHNLQPLHEIPMDRFVMDLKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLN
AVLLPNIHTLFDMSAEDFDAIIAEHFQFGDAVLETDIASFDKSEDDAIAMSALMILEDLGVDQALLDLIEAAFGNITSVHLPTGTRFKFGAMMKSGMFLT
LFINTVVNIMIASRVLRERLTNSPCAAFIGDDNIVKGVKSDALMAERCATWLNMEVKIIDATVGVKAPYFCGGFIVVDQVTGTACRVADPLKRLFKLGKP
LPLDDDQDGDRRRALYDEALRWNRIGITDELIKAVESRYEVFYISLVITALTTLAATVSNFKYIRGNPITLYG
						

Length

2473

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

21-03-2006

Protein Existence

Evidence at transcript 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 28 257 Alphavirus-like MT.
♦ DOMAIN 674 839 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 840 988 (+)RNA virus helicase C-terminal.
♦ DOMAIN 1001 1320 Peptidase C9.
♦ DOMAIN 1328 1486 Macro.
♦ DOMAIN 2230 2345 RdRp catalytic.

Motif(s)

MOTIF 1177 1181 Nuclear localization signal.

Methods of 3D structure generation

Predicted/Modelled

Experimetally known structure

Not Available

Active Site(s)

♦ACT_SITE 1010 1010 For cysteine protease nsP2 activity.
♦ ACT_SITE 1079 1079 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