Results | viHumans

UniProt ID

P13887

Status

Reviewed

Host

Aedes [TaxID: 7158]; Culex Annulirostris (Common Banded Mosquito) [TaxID: 162997]; Homo Sapiens (Human) [TaxID: 9606]; Macropus Sp. (kangaroo) [TaxID: 9322]

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

Ross River Virus (strain NB5092) (RRV)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Togaviridae> Alphavirus (arboviruses Group A)> Ross River Virus> Ross River Virus (strain NB5092) (RRV)

RefSeq

Not Available

PubMed ID

2833022

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

vg:1489706

Reactome

Not Available

Sequence

							MKVTVDVEADSPFLKALQKAFPAFEVESQQVTPNDHANARAFSHLATKLIEQEVPANITILDVGSAPARRLMSDHSYHCICPMKSAEDPERLANYARKLA
KTAGEVLDKNVSGKITDLQDVMATPDLESPTFCLHTDETCRTRAEVAVYQDVXXHAPTSLYHQAMKGVRTVYWIGFDTTPFMFEVVAGAYPTYSTNWADE
QVLQARNIGLCATSLSEGHRGKISIMRKKRLRPSDRXMFSVGXTLYIESRRLLKSWHLPSVFHLKGKNSFTCRCDTIVSCEGYVVKKITMSPGTYGKTVG
YAVTHHAEGFLMCKVTDTVRGERVSFPVCTYVPATICDQMTGILATDVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPVVAQAFSKWAREAKADM
EDEKPLGTRERTLTCCCLWAFKNHKTHTMYKRPDTQTIVKVPSTFDSFVIPSLWSSSLSIGIRQRIKLLLGPKLSRDLPYSGDRNEAREAEKEAEETKEA
ELTREALPPLVGSNCADDVDQVDVEELTYRAGAGVVETPRNALKVTPQERDQLIGAYLILSPQTVLKSEKLTPIHPLAEQVTIMTHSGRSGRYPVDRYDG
RVLVPTGAAIPVSEFQALSESATMVYNEREFINRKLHHIALYGPALNTDEENYEKVRAERAEAEYVFDVDKRTCVKREDASGLVLVGDLINPPFHEFAYE
GLKIRPATPFQTTVIGVFGVPGSGKSAIIKSVVTTRDLVASGKKENCQEIVNDVKKQRGLDVTARTVDSILLNGCRRGVENLYVDEAFACHSGTLLALIA
MVKPTGKVILCGDPKQCGFFNLMQLKVNFNHDICTQVLHKSISRRCTLPITAIVSTLHYQGKMRTTNLCSAPIQIDTTGTTKPAKGDIVLTCFRXWVKQL
QIDYRGHEVMTAAASQGLTRKGVYAVRQKVNENPLYAPSSEHVNVLLTRTENRLVWKTLSGDPWIKVLTNIPKGDFSATLEEWQEEHDNIMNALRERSTA
VDPFQNKAKVCWAKCLVQVLETAGIRMTAEEWDTVLAFREDRAYSPEVALNEICTKYYGVDLDSGLFSAQSVSLYYENNHWDNRPGGRMYGFNREVARKF
EQRYPFLRGKMDSGLQVNVPERKVQPFNAECNILLLNRRLPHALVTSYQQCRGERVEWLLKKLPGYHLLLVSEYNLALPHKRVFWIAPPHVSGADRIYDL
DLGLPLNAGRYDLVFVNIHTEYRTHHYQQCVDHSMKLQMLGGDSLHLLXPGGSLLIRAYGYADRVSEMVVTALARKFSAFRVLRPACVTSNTEVFLLFTN
FDNGRRAVTLHQANQRLSSMFACNGLHTAGCAPSYRVRRTDISGHAEEAVVNAANAKGTVGVGVCRAVARKWPDSFKGAATPVGTAKLVQANGMNVIHAV
GPNFSTVTEAEGDRELAAAYRAVAGIINASNIKSVAIPLLSTGVFSGGKDRVMQSLNHLFTAMDTTDADVVIYCRDKAWEKKIQEAIDRRTAVELVSEDI
SLESDLIRVHPDSCLVGRKGYSITDGKLHSYLEGTRFHQTAVDMAEISTLWPKLQDANEQICLYALGESMDSIRTKCPVEDADSSTPPKTVPCLCRYAMT
AERVARLRMNNTKAIIVCSSFPLPKYRIEGVQKVKCDRVLIFDQTVPSLVSPRKYIPAAASMHADTVSLDSTVSTGSAWSFPSEATYETMEVVAEVHHSE
PPVPPPRRRRAQVTMHHQELLEVSDMHTPIAARVEIPVYDTAVVAERVAIPCTSEYATPIPTPRAVRVVPVPAPRIQRASTYRVSPTPTPRVLRASVCSV
TTSAGVEFPWAPEDLEVLTEPVHCEMREPVELPWEPEDVDIQFGDFETPDKIQFGDIDFDQFLSRAGAYIFSSDTGPGHLQQKSVRQHALPCEMLYAHEE
ERTYPPALDEAREKLLQAKMQMAPTEANKSRYQSRKVENMKAVIIDRLKDGARTYLAEQSEKIPTYASKYPRPVYSPSVEDSLQSPEVAVAACNAFLEAN
YPTVASYQITDEYDAYLDMVDGSESCLDRATFCPAKLRCYPKHHAYHQPQVRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTLDSAVFNVECFKKFA
CNGEYWQEFKDDPIRITTENITTYVTRLKGPKAAALFAKTHNLVPLQEVPMDRFVVDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVR
RLKAVLAPNIHTLFDMSAEDFDAIIAAHFQPGDAVLETDIASFDKSQDDSLALTALMLLEDLGVDQELLDLIEEAFGEITSVHLPTGTRFKFGAMMKSGM
FLTLFINTLLNIVIACRVLREKLTNSICAAFIGDDNIVHGVRSDPLMAERCASWVNMEVKIIDATMCEKPPYFCGGFILYDNVTGSACRVADPLKRLFKL
GKPLPAGDTQDEDRRRALKDETDRWARVGLKSELEIALSSRYEVNGTGNIVRAMATLAKSLKNFKKLRGPIVHLYGGPK
						

Length

2479

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

01-01-1990

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 27 257 Alphavirus-like MT.
♦ DOMAIN 688 840 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 841 989 (+)RNA virus helicase C-terminal.
♦ DOMAIN 1002 1324 Peptidase C9.
♦ DOMAIN 1332 1491 Macro.
♦ DOMAIN 2233 2348 RdRp catalytic.

Motif(s)

MOTIF 1179 1183 Nuclear localization signal.

Methods of 3D structure generation

Predicted/Modelled

Experimetally known structure

Not Available

Active Site(s)

♦ACT_SITE 1011 1011 For cysteine protease nsP2 activity.
♦ ACT_SITE 1080 1080 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