Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
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Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
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(P05769) - Overview - Molecular Target Synopsis

Protein


, Genome polyprotein
Enzyme Classification 3.4.21.91
UniProt P05769

Also Known as POLG_MVEV5

Capsid protein C: Plays a role in virus budding by binding to the cell 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 into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions. Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway., Capsid protein C: Inhibits RNA silencing by interfering with host Dicer., 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 probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, 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 ectodomain. 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 inefficient, 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. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3)., Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response., Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins., 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., Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter., Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the Capsid protein C: Homodimer. Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway. Protein prM: Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi. Envelope protein E: Homodimer; in the endoplasmic reticulum and Golgi. Interacts with protein prM. Interacts with non-structural protein 1. Non-structural protein 1: Homohexamer when secreted. NS1 interacts with NS4B. Interacts with host complement protein CFH; this interaction leads to the degradation of C3. Non-structural protein 2A: Interacts (via N-terminus) with serine protease NS3. Non-structural protein 2B: Forms a heterodimer with serine protease NS3. May form homooligomers. Serine protease NS3: Forms a heterodimer with NS2B. Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity. Non-structural protein 4B: Interacts with serine protease NS3. RNA-directed RNA polymerase NS5: Homodimer. Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation. Interacts with serine protease NS3.

2WV9
CRYSTAL STRUCTURE OF THE NS3 PROTEASE-HELICASE FROM MURRAY VALLEY ENCEPHALITIS VIRUS
RCSB/PDB
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Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
3434P05769-1

Sub-cellular localization


UniProt: is active in the following subcellular-locations: host cytoplasm, host endoplasmic reticulum membrane, host nucleus, host perinuclear region, secreted, virion, virion membrane.
GO terms: is active in the following subcellular-locations: extracellular region, host cell endoplasmic reticulum membrane, host cell nucleus, host cell perinuclear region of cytoplasm, integral component of membrane, viral capsid, viral envelope, virion membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For there are:
8 structures (12 chains) solved
6 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


has been screened with compounds ( bioactivities). (see details)