Results | viHumans

UniProt ID

O90368

Status

Reviewed

Host

Anopheles [TaxID: 44482]; Homo Sapiens (Human) [TaxID: 9606]

Gene Name

Not Available

Protein Name

♦Non-structural polyprotein (Polyprotein nsP1234) (P1234) [Cleaved into: 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)
♦ RNA-directed RNA polymerase nsP4 (EC 2.7.7.48) (Non-structural protein 4) (nsP4)]

Organism Name

O'nyong-nyong Virus (strain SG650) (ONNV)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Togaviridae> Alphavirus (arboviruses Group A)> O'nyong-nyong Virus> O'nyong-nyong Virus (strain SG650) (ONNV)

RefSeq

NC_001512.1 ; M20303.1

PubMed ID

9875334

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MDSVYVDIDADSAFLKALQRAYPMFEVEPKQVTPNDHANARAFSHLAIKLIEQEIDPDSTILDIGPAPARRMMSDRKYHCVCPMRSAEDPERLANYARKL
ASAAGKVTDKNISGKINDLQAVMAVPNMETSTFCLHTDATCKQRGDVAIYQDVYAVHAPTSLYHQAIKGVRVAYWIGFDTTPFMYNAMAGAYPSYSTNWA
DEQVLKAKNIGLCSTDLSEGRRGKLSIMRGKKLKPCDRVLFSVGSTLYPESRKLLQSWHLPSVFHLKGKLSFTCRCDTIVSCEGYVVKRVTMSPGIYGKT
SGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPIVAQAFSKWAKECRK
DMEDEKLLGVRERTLTCCCLWAFRKHKTHTVYKRPDTQSIQKVPAEFDSFVIPSLWSSGLSIPLRTRIKWLLSKAPKHEQLPHSGNAEEAAQAEMDAAEE
REAELTREAMPPLQATQDDVQVEIDVEQLEDRAGAGIVETPRGAIKVTAQPSDRVVGEYLVLTPQAVLRSQKLSLIHALAEQVKTCTHSGRAGRYAVEAY
DGRVLVPSGYAIPQEDFQSLSESATMVFNEREFVNRKLHHIAMHGPALNTDEESYELVRVEKTEHEYVYDVDQKKCCKREEATGLVLVGDLTSPPYHEFA
YEGLKIRPACPYKTAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEISNDVMRQRKLEISARTVDSLLLNGCNKPVEVLYVDEAFACHSGTLLAL
IAMVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYESKMRTTNEYNQPIVVDTTGITKPEPGDLVLTCFRGWVK
QLQIDYRGNEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLIWKTLSGDPWIKILQNPPKGNFKATIKEWEAEHASIMAGICNHQ
MAFDTFQNKANVCWAKCLVPILDTAGIKLSDRQWSQIVQAFKEDRAYSPEVALNEICTRIYGVDLDSGLFSKPLISVYYADNHWDNRPGGKMFGFNPEVA
LMLEKKYPFTKGKWNINKQICITTRKVDEFNPETNIIPANRRLPHSLVAEHHTVRGERMEWLVNKINGHHMLLVSGYNLILPTKRVTWVAPLGTRGADYT
YNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVISVLGRKFRSSRALKPQCITSNTEMFFL
FSRFDNGRRNFTTHVMNNQLNAVYAGLATRAGCAPSYRVKRMDIAKNTEECVVNAANPRGVPGDGVCKAVYRKWPESFRNSATPVGTAKTIMCGQYPVIH
AVGPNFSNYSEAEGDRELASVYREVAKEVSRLGVSSVAIPLLSTGVYSGGKDRLLQSLNHLFTAMDSTDADVVIYCRDKEWEKKITEAISLRSQVELLDD
HISVDCDIVRVHPDSSLAGRKGYSTVEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESVRQKCPVDDADASFPPKTVPCLCRYA
MTPERVARLRMNHTTSIIVCSSFPLPKYKIEGVQKVKCSKALLFDHNVPSRVSPRTYRPADEIIQTPQIPTEACQDAQFVQSITDEAVPVPSDLEACDAT
MDWPSIDIVPTRQRSDSFDSEYSSRSNIQLVTADVHAPMYANSLASSGGSVLSLSSEQAQNGIMILPDSEDTDSISRVSTPIAPPRRRLGRTINVTCDER
EGKILPMASDRLFTAKPYTVALGVSTADITAYPIQAPLGSTQPPALEQITFGDFAEGEIDNLLTGALTFGDFEPGEVEELTDSEWSTCSDTDEELXLDRA
GGYIFSSDTGQGHLQQKSVRQTTLPVNIVEEVHEEKCYPPKLDEIKEQLLLKRLQESASTANRSRYQSRKVENMKATIIHRLKEGCRLYLASDTPRVPSY
RITYPAPVYSPSISIKLNNPETAVAVCNEFLARNYPTVASYQVTDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHSYHAPTIRSAVPSPFQNTLQNV
LAAATKRNCNVTQMRELPTMDSAVFNVECFKKYACNQEYWREFASSPIRVTTENLTMYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTMDMKRDVKVTP
GTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIISTHFKPGDAVLETDIASFDKSQDDSLALTAMMLLEDLGVDQ
PILDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEERLTTSACAAFIGDDNIIHGVVSDALMAARCATWMNMEVKIIDAVV
SEKAPYFCGGFILHDTVTGTSCRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVTRWQRTGLITELEKAVYSRYEVQGITAVITSMATFASSKENFKK
LRGPVVTLYGGPK
						

Length

2513

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

01-11-1998

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 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and 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 is 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 (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: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 .
♦ 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 . 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 (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). .
♦ 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 690 842 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 843 991 (+)RNA virus helicase C-terminal.
♦ DOMAIN 1004 1327 Peptidase C9.
♦ DOMAIN 2267 2382 RdRp catalytic.

Motif(s)

MOTIF 1182 1186 Nuclear localization signal.

Methods of 3D structure generation

Predicted/Modelled

Experimetally known structure

Not Available

Active Site(s)

♦ACT_SITE 1013 1013 For cysteine protease nsP2 activity.
♦ ACT_SITE 1083 1083 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