viHumans
P36328
Reviewed
Bos Taurus (Bovine) [TaxID: 9913]; Didelphis Marsupialis (Southern Opossum) [TaxID: 9268]; Equus Asinus (Donkey) (Equus Africanus Asinus) [TaxID: 9793]; Equus Caballus (Horse) [TaxID: 9796]; Homo Sapiens (Human) [TaxID: 9606]; Melanoconion [TaxID: 53535]; Philander Opossum (Gray Four-eyed Opossum) [TaxID: 9272]; Proechimys [TaxID: 10162]; Sigmodon Hispidus (Hispid Cotton Rat) [TaxID: 42415]
Not Available
♦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)]
Venezuelan Equine Encephalitis Virus (strain P676) (VEEV)
Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Togaviridae> Alphavirus (arboviruses Group A)> Venezuelan Equine Encephalitis Virus> Venezuelan Equine Encephalitis Virus (strain P676) (VEEV)
NC_001449.1 ;  L04653.1 
1448915 ;  8709783 ;  11390583 ;  16485478 ;  26041283 
Various pathway(s) in which protein is involved
vg:2652923
Not Available
MEKVHVDIEEDSPFLRALQRSFPQFEVEAKQVTDNDHANARAFSHLASKLIETEVDPSDTILDIGSAPARRMYSKHKYHCICPMRCAEDPDRLYKYATKL
KKNCKEITDKELDKKMKELAAVMSDPDLETETMCLHDDESCRYEGQVAVYQDVYAVDGPTSLYHQANKGVRVAYWIGFDTTPFMFKNLAGAYPSYSTNWA
DETVLTARNIGLCSSDVMERSRRGMSILRKKYLKPSNNVLFSVGSTIYHEKRDLLRSWHLPSVFHLRGKQNYTCRCETIVSCDGYVVKRIAISPGLYGKP
SGYAATMHREGFLCCKVTDTLNGERVSFPVCTYVPATLCDQMTGILATDVSADDAQKLLVGLNQRIVVNGRTQRNTNTMKNYLLPVVAQAFARWAKEYKE
DQEDERPLGLRDRQLVMGCCWAFRRHKITSIYKRPDTQTIIKVNSDFHSFVLPRIGSNTLEIGLRTRIRKMLEEHKEPSPLITAEDIQEAKCAADEAKEV
REAEELRAALPPLAADFEEPTLEADVDLMLQEAGAGSVETPRGLIKVTSYAGEDKIGSYAVLSPQAVLKSEKLSCIHPLAEQVIVITHSGRKGRYAVEPY
HGKVVVPEGHAIPVQDFQALSESATIVYNEREFVNRYLHHIATHGGALNTDEEYYKTVKPSEHDGEYLYDIDRKQCVKKELVTGLGLTGELVDPPFHEFA
YESLRTRPAAPYQVPTIGVYGVPGSGKSGIIKSAVTKKDLVVSAKKENCAEIIRDVKKMKGLDVNARTVDSVLLNGCKHPVETLYIDEAFACHAGTLRAL
IAIIRPKKAVLCGDPKQCGFFNMMCLKVHFNHEICTQVFHKSISRRCTKSVTSVVSTLFYDKRMRTTNPKETKIVIDTTGSTKPKQDDLILTCFRGWVKQ
LQIDYKGNEIMTAAASQGLTRKGVYAVRYKVNENPLYAPTSEHVNVLLTRTEDRIVWKTLAGDPWIKILTAKYPGNFTATIEEWQAEHDAIMRHILERPD
PTDVFQNKANVCWAKALVPVLKTAGIDMTTEQWNTVDYFETDKAHSAEIVLNQLCVRFFGLDLDSGLFSAPTVPLSIRNNHWDNSPSPNMYGLNKEVVRQ
LSRRYPQLPRAVATGRVYDMNTGTLRNYDPRINLVPVNRRLPHALVLHHNEHPQSDFSSFVSKLKGRTVLVVGEKLSVPGKKVDWLSDQPEATFRARLDL
GIPGDVPKYDIVFINVRTPYKYHHYQQCEDHAIKLSMLTKKACLHLNPGGTCVSIGYGYADRASESIIGAIARQFKFSRVCKPKSSHEETEVLFVFIGYD
RKARTHNPYKLSSTLTNIYTGSRLHEAGCAPSYHVVRGDIATATEGVIINAANSKGQPGGGVCGALYKKFPESFDLQPIEVGKARLVKGAAKHIIHAVGP
NFNKVSEVEGDKQLAEAYESIAKIVNDNNYKSVAIPLLSTGIFSGNKDRLTQSLNHLLTALDTTDADVAIYCRDKKWEMTLKEAVARREAVEEICISDDS
SVTEPDAELVRVHPKSSLAGRKGYSTSDGKTFSYLEGTKFHQAAKDIAEINAMWPVATEANEQVCMYILGESMSSIRSKCPVEESEASTPPSTLPCLCIH
AMTPERVQRLKASRPEQITVCSSFPLPKYRITGVQKIQCSQPILFSPKVPAYIHPRKYLVETPPVEETPESPAENQSTEGTPEQPALVNVDATRTRMPEP
IIIEEEEEDSISLLSDGPTHQVLQVEADIHGSPSVSSSSWSIPHASDFDVDSLSILDTLDGASVTSGAVSAETNSYFARSMEFRARPVPAPRTVFRNPPH
PAPRTRTPPLAHSRASSRTSLVSTPPGVNRVITREELEALTPSRAPSRSASRTSLVSNPPGVNRVITREEFEAFVAQQQRFDAGAYIFSSDTGQGHLQQK
SVRQTVLSEVVLERTELEISYAPRLDQEKEELLRKKLQLNPTPANRSRYQSRRVENMKAITARRILQGLGHYLKAEGKVECYRTLHPVPLYSSSVNRAFS
SPKVAVEACNAMLKENFPTVASYCIIPEYDAYLDMVDGASCCLDTASFCPAKLRSFPKKHSYLEPTIRSAVPSAIQNTLQNVLAAATKRNCNVTQMRELP
VLDSAAFNVECFKKYACNNEYWETFKENPIRLTEENVVNYITKLKGPKAAALFAKTHNLNMLQDIPMDRFVMDLKRDVKVTPGTKHTEERPKVQVIQAAD
PLATADLCGIHRELVRRLNAVLLPNIHTLFDMSAEDFDAIIAEHFQPGDCVLETDIASFDKSEDDAMALTALMILEDLGVDAELLTLIEAAFGEISSIHL
PTKTKFKFGAMMKSGMFLTLFVNTVINIVIASRVLRERLTGSPCAAFIGDDNIVKGVKSDKLMADRCATWLNMEVKIIDAVVGEKAPYFCGGFILCDSVT
GTACRVADPLKRLFKLGKPLAVDDEHDDDRRRALHEESTRWNRVGILPELCKAVESRYETVGTSIIVMAMTTLASSVKSFSYLRGAPITLYG
2492
Not Available
Not Available
01-06-1994
Evidence at protein level
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)
% Number of Residues in Helices % Number of Residues in Strands % Number of Residues in Coils
♦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).
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  
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  
♦ 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 28 259 Alphavirus-like MT.
♦ DOMAIN 690 841 (+)RNA virus helicase ATP-binding.
♦ DOMAIN 842 990 (+)RNA virus helicase C-terminal.
♦ DOMAIN 1003 1322 Peptidase C9.
♦ DOMAIN 1330 1489 Macro.
♦ DOMAIN 2249 2364 RdRp catalytic.
MOTIF 1179 1183 Nuclear localization signal.
X-ray crystallography (2); NMR spectroscopy (1)
3GQE  3GQO  5ISN  
♦ACT_SITE 1012 1012 For cysteine protease nsP2 activity.
♦ ACT_SITE 1081 1081 For cysteine protease nsP2 activity.
Protein couldn't be modeled using I-Tasser and Raptor X because of length constraints of the software.
Not Available
Virtual screening has been performed using RASPD
  • Million Molecules

Best 20 Hit molecules

    Not Available