Results | viHumans

UniProt ID

P27909

Status

Reviewed

Host

Aedes Aegypti (Yellowfever Mosquito) (Culex Aegypti) [TaxID: 7159]; Aedes Albopictus (Asian Tiger Mosquito) (Stegomyia Albopicta) [TaxID: 7160]; Homo Sapiens (Human) [TaxID: 9606]

Gene Name

Not Available

Protein Name

♦Genome polyprotein [Cleaved into: Protein C (Core protein)
♦ Protein prM
♦ Peptide pr
♦ Small envelope protein M (Matrix protein)
♦ Envelope protein E
♦ Non-structural protein 1 (NS1)
♦ Non-structural protein 2A (NS2A)
♦ Non-structural protein 2A-alpha (NS2A-alpha)
♦ Serine protease subunit NS2B (Flavivirin protease NS2B regulatory subunit) (Non-structural protein 2B)
♦ Serine protease NS3 (EC 3.4.21.91) (EC 3.6.1.15) (EC 3.6.4.13) (Flavivirin protease NS3 catalytic subunit) (Non-structural protein 3)
♦ Non-structural protein 4A (NS4A)
♦ Peptide 2k
♦ Non-structural protein 4B (NS4B)
♦ RNA-directed RNA polymerase NS5 (EC 2.1.1.56) (EC 2.1.1.57) (EC 2.7.7.48) (Non-structural protein 5)]

Organism Name

Dengue Virus Type 1 (strain Brazil/97-11/1997) (DENV-1)

Taxonomic Lineage

Viruses> SsRNA Viruses> SsRNA Positive-strand Viruses> No DNA Stage> Flaviviridae> Flavivirus (arboviruses Group B)> Dengue Virus Group> Dengue Virus> Dengue Virus 1> Dengue Virus Type 1 (strain Brazil/97-11/1997) (DENV-1)

RefSeq

NC_001477.1 ; U88536.1

PubMed ID

2738579 ; 1339466 ; 12457974

Pathways Involved

Various pathway(s) in which protein is involved

KEGG

Not Available

Reactome

Not Available

Sequence

							MNNQRKKTGRPSFNMLKRARNRVSTGSQLAKRFSKGLLSGQGPMKLVMAFIAFLRFLAIPPTAGILARWSSFKKNGAIKVLRGFKKEISSMLNIMNRRKR
SVTMLLMLLPTALAFHLTTRGGEPHMIVSKQERGKSLLFKTSAGVNMCTLIAMDLGELCEDTMTYKCPRITEAEPDDVDCWCNATDTWVTYGTCSQTGEH
RRDKRSVALAPHVGLGLETRTETWMSSEGAWKQIQKVETWALRHPGFTVIALFLAHAIGTSITQKGIIFILLMLVTPSMAMRCVGIGNRDFVEGLSGATW
VDVVLEHGSCVTTMAKNKPTLDIELLKTEVTNPAVLRKLCIEAKISNTTTDSRCPTQGEATLVEEQDANFVCRRTFVDRGWGNGCGLFGKGSLLTCAKFK
CVTKLEGKIVQYENLKYSVIVTVHTGDQHQVGNETTEHGTIATITPQAPTSEIQLTDYGALTLDCSPRTGLDFNEMVLLTMKEKSWLVHKQWFLDLPLPW
TSGASTSQETWNRQDLLVTFKTAHAKKQEVVVLGSQEGAMHTALTGATEIQTSGTTTIFAGHLKCRLKMDKLTLKGTSYVMCTGSFKLEKEVAETQHGTV
LVQVKYEGTDAPCKIPFSTQDEKGVTQNGRLITANPIVTDKEKPVNIETEPPFGESYIVVGAGEKALKLSWFKKGSSIGKMFEATARGARRMAILGDTAW
DFGSIGGVFTSVGKLVHQVFGTAYGVLFSGVSWTMKIGIGILLTWLGLNSRSTSLSMTCIAVGMVTLYLGVMVQADSGCVINWKGRELKCGSGIFVTNEV
HTWTEQYKFQADSPKRLSAAIGRAWEEGVCGIRSATRLENIMWKQISNELNHILLENDIKFTVVVGNANGILAQGKKMIRPQPMEHKYSWKSWGKAKIIG
ADIQNTTFIIDGPDTPECPDEQRAWNIWEVEDYGFGIFTTNIWLKLRDSYTQMCDHRLMSAAIKDSKAVHADMGYWIESEKNETWKLARASFIEVKTCIW
PKSHTLWSNGVLESEMIIPKMYGGPISQHNYRPGYFTQTAGPWHLGKLELDFDLCEGTTVVVDEHCGSRGPSLRTTTVTGKIIHEWCCRSCTLPPLRFRG
EDGCWYGMEIRPVKEKEENLVRSMVSAGSGEVDSFSLGILCVSIMIEEVMRSRWSRKMLMTGTLAVFLLLIMGQLTWNDLIRLCIMVGANASDKMGMGTT
YLALMATFKMRPMFAVGLLFRRLTSREVLLLTIGLSLVASVELPNSLEELGDGLAMGIMMLKLLTEFQPHQLWTTLLSLTFIKTTLSLDYAWKTTAMVLS
IVSLFPLCLSTTSQKTTWLPVLLGSFGCKPLTMFLITENEIWGRKSWPLNEGIMAIGIVSILLSSLLKNDVPLAGPLIAGGMLIACYVISGSSADLSLEK
AAEVSWEEEAEHSGTSHNILVEVQDDGTMKIKDEERDDTLTILLKATLLAVSGVYPMSIPATLFVWYFWQKKKQRSGVLWDTPSPPEVERAVLDDGIYRI
LQRGLLGRSQVGVGVFQDGVFHTMWHVTRGAVLMYQGKRLEPSWASVKKDLISYGGGWRFQGSWNTGEEVQVIAVEPGKNPKNVQTTPGTFKTPEGEVGA
IALDFKPGTSGSPIVNREGKIVGLYGNGVVTTSGTYVSAIAQAKASQEGPLPEIEDEVFKKRNLTIMDLHPGSGKTRRYLPAIVREAIKRKLRTLILAPT
RVVASEMAEALKGMPIRYQTTAVKSEHTGREIVDLMCHATFTMRLLSPVRVPNYNMIIMDEAHFTDPASIAARGYISTRVGMGEAAAIFMTATPPGSVEA
FPQSNAVIQDEERDIPERSWNSGYDWITDFPGKTVWFVPSIKSGNDIANCLRKNGKRVIQLSRKTFDTEYQKTKNNDWDYVVTTDISEMGANFRADRVID
PRRCLKPVILKDGPERVILAGPMPVTVASAAQRRGRIGRNQNKEGDQYVYMGQPLNNDEDHAHWTEAKMLLDNINTPEGIIPALFEPEREKSAAIDGEYR
LRGEARKTFVELMRRGDLPVWLSYKVASEGFQYSDRRWCFDGERNNQVLEENMDVEIWTKEGERKKLRPRWLDARTYSDPLALREFKEFAAGRRSVSGDL
ILEIGKLPQHLTLRAQNALDNLVMLHNSEQGGKAYRHAMEELPDTIETLMLLALIAVLTGGVTLFFLSGKGLGKTSIGLLCVTASSALLWMASVEPHWIA
ASIILEFFLMVLLIPEPDRQRTPQDNQLAYVVIGLLFMILTVAANEMGLLETTKKDLGIGHVAAENHQHATILDVDLHPASAWTLYAVATTVITPMMRHT
IENTTANISLTAIANQAAILMGLDKGWPISKMDLGVPLLALGCYSQVNPLTLTAAVLMLVAHYAIIGPGLQAKATREAQKRTAAGIMKNPTVDGIVAIDL
DPVVYDAKFEKQLGQIMLLILCTSQILLMRTTWALCESITLATGPLTTLWEGSPGKFWNTTIAVSMANIFRGSYLAGAGLAFSLMKSLGGGRRGTGAQGE
TLGEKWKRQLNQLSKSEFNTYKRSGIMEVDRSEAKEGLKRGETTKHAVSRGTAKLRWFVERNLVKPEGKVIDLGCGRGGWSYYCAGLKKVTEVKGYTKGG
PGHEEPIPMATYGWNLVKLHSGKDVFFMPPEKCDTLLCDIGESSPNPTIEEGRTLRVLKMVEPWLRGNQFCIKILNPYMPSVVETLEQMQRKHGGMLVRN
PLSRNSTHEMYWVSCGTGNIVSAVNMTSRMLLNRFTMAHRKPTYERDVDLGAGTRHVAVEPEVANLDIIGQRIENIKNEHKSTWHYDEDNPYKTWAYHGS
YEVKPSGSASSMVNGVVRLLTKPWDVIPMVTQIAMTDTTPFGQQRVFKEKVDTRTPRAKRGTAQIMEVTAKWLWGFLSRNKKPRICTREEFTRKVRSNAA
IGAVFVDENQWNSAKEAVEDERFWDLVHRERELHKQGKCATCVYNMMGKREKKLGEFGKAKGSRAIWYMWLGARFLEFEALGFMNEDHWFSRENSLSGVE
GEGLHKLGYILRDISKIPGGNMYADDTAGWDTRITEDDLQNEAKITDIMEPEHALLATSIFKLTYQNKVVRVQRPAKNGTVMDVISRRDQRGSGQVGTYG
LNTFTNMEVQLIRQMESEGIFFPSELESPNLAERVLDWLEKHGAERLKRMAISGDDCVVKPIDDRFATALIALNDMGKVRKDIPQWEPSKGWNDWQQVPF
CSHHFHQLIMKDGREIVVPCRNQDELVGRARVSQGAGWSLRETACLGKSYAQMWQLMYFHRRDLRLAANAICSAVPVDWVPTSRTTWSIHAHHQWMTTED
MLSVWNRVWIEENPWMEDKTHVSSWEEVPYLGKREDQWCGSLIGLTARATWATNIQVAINQVRRLIGNENYLDYMTSMKRFKNESDPEGALW
						

Length

3392

Alternate Sequence

Not Available

Non-standard residue

Not Available

Date of last Sequence modification

12-12-2006

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)

♦Protein C: Plays a role in virus budding by binding to membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration in host cytoplasm after hemifusion induced by surface proteins. Can migrate tot cell nucleus where it modulates host functions.
♦ Peptide pr: Prevents premature fusion activity of envelope proteins in trans Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space gets dissociated from E dimers.
♦ Protein prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network. Presumably to avoid catastrophic activation of the viral fusion activity in acidic GolGi compartment prior to virion release. prM-E cleavage is ineficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.
♦ Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M extodomain. May display a viroporin activity.
♦ Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is ineficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.
♦ Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. May play a role in viral genome replication. Assist membrane bending and envelopment of genomic RNA at the endoplasmic reticulum. Excreted as a hexameric lipoparticle that plays a role against host immune responce.
♦ Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.
♦ Non-structural protein 2B: Required cofactor for the serine protease function of NS3 (By similarity). May have membrane-destabilizing activity and form viroporins (By similarity).
♦ Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction.
♦ Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. Plays a role in the inhibition of the host innate immune response. Interacts with host MAVS and thereby prevents the interaction between DDX58 and MAVS. In turn, IFN-beta production is impaired.
♦ Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.
♦ Non-structural protein 4B: Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.
♦ RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.

EC

3.4.21.91 , 3.6.1.15 , 3.6.4.13 , 2.1.1.56 , 2.1.1.57 , 2.7.7.48

Experimentally known GO terms

GO:0003724 ;   GO:0003725 ;   GO:0003968 ;   GO:0004252 ;   GO:0004482 ;
GO:0004483 ;   GO:0005198 ;   GO:0005216 ;   GO:0005524 ;   GO:0005576 ;
GO:0006351 ;   GO:0006355 ;   GO:0008026 ;   GO:0016021 ;   GO:0019028 ;
GO:0019031 ;   GO:0019062 ;   GO:0033650 ;   GO:0039502 ;   GO:0039520 ;
GO:0039545 ;   GO:0039564 ;   GO:0039574 ;   GO:0039654 ;   GO:0039694 ;
GO:0039707 ;   GO:0042025 ;   GO:0044167 ;   GO:0044385 ;   GO:0046872 ;
GO:0046983 ;   GO:0051259 ;   GO:0055036 ;   GO:0075512

Subcellular Location

♦ Protein C: Virion . Host nucleus .
♦ Peptide pr: Secreted .
♦ Small envelope protein M: Virion membrane
♦ Multi-pass membrane protein . Host endoplasmic reticulum membrane , PROSITE-ProRule:PRU00860
♦ Multi-pass membrane protein .
♦ Envelope protein E: Virion membrane
♦ Multi-pass membrane protein . Host endoplasmic reticulum membrane , PROSITE-ProRule:PRU00860
♦ Multi-pass membrane protein .
♦ Non-structural protein 1: Secreted . Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Peripheral membrane protein PROSITE-ProRule:PRU00860
♦ Lumenal side .
♦ Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Multi-pass membrane protein .
♦ Non-structural protein 2A: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Multi-pass membrane protein .
♦ Serine protease subunit NS2B: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Peripheral membrane protein PROSITE-ProRule:PRU00860
♦ Cytoplasmic side , PROSITE-ProRule:PRU00860.
♦ Serine protease NS3: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Peripheral membrane protein PROSITE-ProRule:PRU00860
♦ Cytoplasmic side PROSITE-ProRule:PRU00860. Note=Remains non-covalently associated to NS3 protease. PROSITE-ProRule:PRU00860.
♦ Non-structural protein 4A: Host endoplasmic reticulum membrane
♦ Multi-pass membrane protein . Host mitochondrion . Note=Located in RE-associated vesicles hosting the replication complex. Interacts with host MAVS in the mitochondrion-associated endoplasmic reticulum membranes. .
♦ Non-structural protein 4B: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Multi-pass membrane protein .
♦ RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane PROSITE-ProRule:PRU00860
♦ Peripheral membrane protein PROSITE-ProRule:PRU00860
♦ Cytoplasmic side PROSITE-ProRule:PRU00860. Host nucleus . Note=Located in RE-associated vesicles hosting the replication complex. .

Domain(s)

♦DOMAIN 1476 1653 Peptidase S7.
♦ DOMAIN 1656 1812 Helicase ATP-binding.
♦ DOMAIN 1822 1989 Helicase C-terminal.
♦ DOMAIN 2495 2756 mRNA cap 0-1 NS5-type MT.
♦ DOMAIN 3021 3170 RdRp catalytic.

Motif(s)

MOTIF 1760 1763 DEAH box.

Methods of 3D structure generation

X-ray crystallography (1)

Experimetally known structure

3UZQ

Active Site(s)

♦ACT_SITE 1526 1526 Charge relay system
♦ for serine protease NS3 activity.
♦ ACT_SITE 1550 1550 Charge relay system
♦ for serine protease NS3 activity.
♦ ACT_SITE 1610 1610 Charge relay system
♦ for serine protease NS3 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