UniProt functional annotation for P19712



	UniProt functional annotation for P19712

UniProt code: P19712.

Organism: Classical swine fever virus (strain Alfort) (CSFV) (Hog cholera virus).

Taxonomy: Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes; Amarillovirales; Flaviviridae; Pestivirus.

Function: [N-terminal protease]: Leader cysteine autoprotease that cleaves itself from the nascent polyprotein during translation of the viral mRNA. Once released, plays a role in the inhibition of host innate immune response by interacting with host IRF3 and inducing its proteasomal degradation. {ECO:0000269|PubMed:17215286, ECO:0000269|PubMed:24606708, ECO:0000269|PubMed:27334592}.

Function: [Capsid protein C]: Packages viral RNA to form a viral nucleocapsid and thereby protects viral RNA. Plays also a role in transcription regulation. Protects the incoming virus against IFN- induced effectors. {ECO:0000269|PubMed:28290554, ECO:0000269|PubMed:9617770}.

Function: [E(rns) glycoprotein]: Plays a role in viral entry. Interacts with host RPSA that acts as a cellular attachment receptor for the virus. Possesses also intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferon and assist in the development of persistent infections. {ECO:0000269|PubMed:19264773, ECO:0000269|PubMed:19767841, ECO:0000269|PubMed:25694590, ECO:0000269|PubMed:29235980, ECO:0000269|PubMed:8356450}.

Function: [Envelope glycoprotein E1]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E2 the viral entry. {ECO:0000269|PubMed:15527858}.

Function: [Envelope glycoprotein E2]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E1 the viral entry. {ECO:0000269|PubMed:15527858}.

Function: [Viroporin p7]: Plays an essential role in the virus replication cycle by acting as a viroporin. Forms ion conductive pores, which alters the cell permeability allowing the transport of ions and other small molecules. {ECO:0000269|PubMed:22496228, ECO:0000269|PubMed:24189547}.

Function: [Non-structural protein 2-3]: Autoprotease that associates with the host chaperone JIV and cleaves the NS2-3 protein between NS2 and NS3. Plays also a role in the formation of infectious particles. {ECO:0000269|PubMed:17482232}.

Function: [Cysteine protease NS2]: Plays a role in the regulation of viral RNA replication. {ECO:0000269|PubMed:10438869}.

Function: [Serine protease NS3]: Multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and viral genome replication. The chymotrypsin-like serine protease activity utilizes NS4A as an essential cofactor and catalyzes the cleavage of the polyprotein leading to the release of NS4A, NS4B, NS5A, and NS5B. Plays a role in the inhibition of host NF-kappa-B activation by interacting with and inhibiting host TRAF6. Interacts with NS5B to enhance RNA-dependent RNA polymerase activity. {ECO:0000269|PubMed:19185595, ECO:0000269|PubMed:28751780}.

Function: [Non-structural protein 4A]: Acts as a cofactor for the NS3 protease activity. {ECO:0000269|PubMed:17482232}.

Function: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). Antagonizes host cell apoptosis by interacting with host ferritin heavy chain. The ORF4 protein physically binds host FTH1/FHC, resulting in the reduction of FTH1 protein levels in host cells. Reduction of FTH1 concentration further inhibits the accumulation of reactive oxygen in host cells, leading to reduced apoptosis (PubMed:29844394) (By similarity). {ECO:0000250|UniProtKB:O56125, ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000269|PubMed:29844394}.

Function: [Non-structural protein 5A]: Regulates viral RNA replication by interacting with the 3'-untranslated region of viral RNA in a dose- dependent manner. At small concentrations promotes viral synthesis by interacting with the polymerase NS5B while at large concentrations, inhibits replication. {ECO:0000269|PubMed:22261205, ECO:0000269|PubMed:22795973}.

Function: [RNA-directed RNA polymerase]: Replicates the viral (+) and (-) genome. {ECO:0000255|PROSITE-ProRule:PRU00539}.

Catalytic activity: [Serine protease NS3]: Reaction=Leu is conserved at position P1 for all four cleavage sites. Alanine is found at position P1' of the NS4A-NS4B cleavage site, whereas serine is found at position P1' of the NS3-NS4A, NS4B-NS5A and NS5A-NS5B cleavage sites.; EC=3.4.21.113;

Catalytic activity: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};

Catalytic activity: [Serine protease NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;

Catalytic activity: [Serine protease NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;

Subunit: [N-terminal protease]: Interacts with host IRF3. {ECO:0000269|PubMed:17215286, ECO:0000269|PubMed:27334592}.

Subunit: [Capsid protein C]: Interacts with host OS9 (PubMed:25010283). {ECO:0000269|PubMed:25010283}.

Subunit: [E(rns) glycoprotein]: Homodimer; disulfide-linked (PubMed:29235980, PubMed:1870198). Interacts with host RPSA (PubMed:25694590). {ECO:0000269|PubMed:1870198, ECO:0000269|PubMed:25694590, ECO:0000269|PubMed:29235980}.

Subunit: [Envelope glycoprotein E1]: Homodimer; disulfide-linked (PubMed:2370675). Heterodimer with E1; disulfide-linked (PubMed:2370675). {ECO:0000269|PubMed:2370675}.

Subunit: [Envelope glycoprotein E2]: Homodimer; disulfide-linked (PubMed:2370675). Heterodimer with E1; disulfide-linked (PubMed:2370675). Interacts with host TRX2 (PubMed:26041303). {ECO:0000269|PubMed:2370675, ECO:0000269|PubMed:26041303}.

Subunit: [Serine protease NS3]: Interacts with host TRAF6; this interaction inhibits host NF-kappa-B pathway. Interacts with NS5B; this interaction enhances RNA-dependent RNA polymerase activity. Interacts with protein NS4A. {ECO:0000305}.

Subunit: [Non-structural protein 4B]: Interacts with host RAB5, this interaction facilitates the formation of NS4B-related complex (PubMed:28848503). Interacts with host FTH1; this interaction plays a positive role in viral anti-apoptosis (PubMed:29844394). {ECO:0000269|PubMed:28848503, ECO:0000269|PubMed:29844394}.

Subunit: [Non-structural protein 5A]: Interacts with RNA-directed RNA polymerase (PubMed:22795973). Interacts with host RSAD2; this interaction inhibits viral replication (PubMed:31517388). {ECO:0000269|PubMed:22795973, ECO:0000269|PubMed:31517388}.

Subunit: [RNA-directed RNA polymerase]: Interacts with NS5A; this interaction promotes viral replication. {ECO:0000269|PubMed:22795973, ECO:0000269|PubMed:31517388}.

Subcellular location: [N-terminal protease]: Host cytoplasm {ECO:0000269|PubMed:17215286}.

Subcellular location: [Capsid protein C]: Virion {ECO:0000269|PubMed:28290554}.

Subcellular location: [E(rns) glycoprotein]: Host cell membrane {ECO:0000269|PubMed:28290554}; Peripheral membrane protein. Virion membrane {ECO:0000269|PubMed:28290554}; Peripheral membrane protein {ECO:0000305}. Note=The C-terminus membrane anchor of Erns represents an amphipathic helix embedded in plane into the membrane.

Subcellular location: [Envelope glycoprotein E2]: Host cell surface {ECO:0000269|PubMed:28290554}. Virion membrane {ECO:0000269|PubMed:28290554}.

Subcellular location: [Cysteine protease NS2]: Host membrane {ECO:0000255|PROSITE-ProRule:PRU01029}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU01029}.

Subcellular location: [Serine protease NS3]: Host cytoplasm {ECO:0000269|PubMed:28848503}.

Subcellular location: [Non-structural protein 4B]: Host cytoplasm {ECO:0000269|PubMed:28848503, ECO:0000269|PubMed:29844394}.

Subcellular location: [Non-structural protein 5A]: Host cytoplasm {ECO:0000269|PubMed:28848503}.

Induction: Translated cap independently from an internal ribosome entry site (IRES). {ECO:0000269|PubMed:9573242}.

Ptm: [E(rns) glycoprotein]: Heavily glycosylated. {ECO:0000269|PubMed:1870198}.

Ptm: The viral RNA of pestiviruses is expressed as a single polyprotein which undergoes post-translational proteolytic processing resulting in the production of at least eleven individual proteins. The N-terminal protease cleaves itself from the nascent polyprotein autocatalytically and thereby generates the N-terminus of the adjacent viral capsid protein C. {ECO:0000269|PubMed:8230432, ECO:0000269|PubMed:8388499}.

Ptm: [Genome polyprotein]: Cleavage between E2 and p7 is partial.

Similarity: Belongs to the pestivirus polyprotein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Classical swine fever virus (strain Alfort) (CSFV) (Hog cholera virus).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes; Amarillovirales; Flaviviridae; Pestivirus.



Function:		[N-terminal protease]: Leader cysteine autoprotease that cleaves itself from the nascent polyprotein during translation of the viral mRNA. Once released, plays a role in the inhibition of host innate immune response by interacting with host IRF3 and inducing its proteasomal degradation. {ECO:0000269\|PubMed:17215286, ECO:0000269\|PubMed:24606708, ECO:0000269\|PubMed:27334592}.



Function:		[Capsid protein C]: Packages viral RNA to form a viral nucleocapsid and thereby protects viral RNA. Plays also a role in transcription regulation. Protects the incoming virus against IFN- induced effectors. {ECO:0000269\|PubMed:28290554, ECO:0000269\|PubMed:9617770}.



Function:		[E(rns) glycoprotein]: Plays a role in viral entry. Interacts with host RPSA that acts as a cellular attachment receptor for the virus. Possesses also intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferon and assist in the development of persistent infections. {ECO:0000269\|PubMed:19264773, ECO:0000269\|PubMed:19767841, ECO:0000269\|PubMed:25694590, ECO:0000269\|PubMed:29235980, ECO:0000269\|PubMed:8356450}.



Function:		[Envelope glycoprotein E1]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E2 the viral entry. {ECO:0000269\|PubMed:15527858}.



Function:		[Envelope glycoprotein E2]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E1 the viral entry. {ECO:0000269\|PubMed:15527858}.



Function:		[Viroporin p7]: Plays an essential role in the virus replication cycle by acting as a viroporin. Forms ion conductive pores, which alters the cell permeability allowing the transport of ions and other small molecules. {ECO:0000269\|PubMed:22496228, ECO:0000269\|PubMed:24189547}.



Function:		[Non-structural protein 2-3]: Autoprotease that associates with the host chaperone JIV and cleaves the NS2-3 protein between NS2 and NS3. Plays also a role in the formation of infectious particles. {ECO:0000269\|PubMed:17482232}.



Function:		[Cysteine protease NS2]: Plays a role in the regulation of viral RNA replication. {ECO:0000269\|PubMed:10438869}.



Function:		[Serine protease NS3]: Multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and viral genome replication. The chymotrypsin-like serine protease activity utilizes NS4A as an essential cofactor and catalyzes the cleavage of the polyprotein leading to the release of NS4A, NS4B, NS5A, and NS5B. Plays a role in the inhibition of host NF-kappa-B activation by interacting with and inhibiting host TRAF6. Interacts with NS5B to enhance RNA-dependent RNA polymerase activity. {ECO:0000269\|PubMed:19185595, ECO:0000269\|PubMed:28751780}.



Function:		[Non-structural protein 4A]: Acts as a cofactor for the NS3 protease activity. {ECO:0000269\|PubMed:17482232}.



Function:		[Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex (By similarity). Antagonizes host cell apoptosis by interacting with host ferritin heavy chain. The ORF4 protein physically binds host FTH1/FHC, resulting in the reduction of FTH1 protein levels in host cells. Reduction of FTH1 concentration further inhibits the accumulation of reactive oxygen in host cells, leading to reduced apoptosis (PubMed:29844394) (By similarity). {ECO:0000250\|UniProtKB:O56125, ECO:0000250\|UniProtKB:Q9Q6P4, ECO:0000269\|PubMed:29844394}.



Function:		[Non-structural protein 5A]: Regulates viral RNA replication by interacting with the 3'-untranslated region of viral RNA in a dose- dependent manner. At small concentrations promotes viral synthesis by interacting with the polymerase NS5B while at large concentrations, inhibits replication. {ECO:0000269\|PubMed:22261205, ECO:0000269\|PubMed:22795973}.



Function:		[RNA-directed RNA polymerase]: Replicates the viral (+) and (-) genome. {ECO:0000255\|PROSITE-ProRule:PRU00539}.


Catalytic activity:		[Serine protease NS3]: Reaction=Leu is conserved at position P1 for all four cleavage sites. Alanine is found at position P1' of the NS4A-NS4B cleavage site, whereas serine is found at position P1' of the NS3-NS4A, NS4B-NS5A and NS5A-NS5B cleavage sites.; EC=3.4.21.113;
Catalytic activity:		[RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA- COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00539};
Catalytic activity:		[Serine protease NS3]: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
Catalytic activity:		[Serine protease NS3]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
Subunit:		[N-terminal protease]: Interacts with host IRF3. {ECO:0000269\|PubMed:17215286, ECO:0000269\|PubMed:27334592}.
Subunit:		[Capsid protein C]: Interacts with host OS9 (PubMed:25010283). {ECO:0000269\|PubMed:25010283}.
Subunit:		[E(rns) glycoprotein]: Homodimer; disulfide-linked (PubMed:29235980, PubMed:1870198). Interacts with host RPSA (PubMed:25694590). {ECO:0000269\|PubMed:1870198, ECO:0000269\|PubMed:25694590, ECO:0000269\|PubMed:29235980}.
Subunit:		[Envelope glycoprotein E1]: Homodimer; disulfide-linked (PubMed:2370675). Heterodimer with E1; disulfide-linked (PubMed:2370675). {ECO:0000269\|PubMed:2370675}.
Subunit:		[Envelope glycoprotein E2]: Homodimer; disulfide-linked (PubMed:2370675). Heterodimer with E1; disulfide-linked (PubMed:2370675). Interacts with host TRX2 (PubMed:26041303). {ECO:0000269\|PubMed:2370675, ECO:0000269\|PubMed:26041303}.
Subunit:		[Serine protease NS3]: Interacts with host TRAF6; this interaction inhibits host NF-kappa-B pathway. Interacts with NS5B; this interaction enhances RNA-dependent RNA polymerase activity. Interacts with protein NS4A. {ECO:0000305}.
Subunit:		[Non-structural protein 4B]: Interacts with host RAB5, this interaction facilitates the formation of NS4B-related complex (PubMed:28848503). Interacts with host FTH1; this interaction plays a positive role in viral anti-apoptosis (PubMed:29844394). {ECO:0000269\|PubMed:28848503, ECO:0000269\|PubMed:29844394}.
Subunit:		[Non-structural protein 5A]: Interacts with RNA-directed RNA polymerase (PubMed:22795973). Interacts with host RSAD2; this interaction inhibits viral replication (PubMed:31517388). {ECO:0000269\|PubMed:22795973, ECO:0000269\|PubMed:31517388}.
Subunit:		[RNA-directed RNA polymerase]: Interacts with NS5A; this interaction promotes viral replication. {ECO:0000269\|PubMed:22795973, ECO:0000269\|PubMed:31517388}.
Subcellular location:		[N-terminal protease]: Host cytoplasm {ECO:0000269\|PubMed:17215286}.
Subcellular location:		[Capsid protein C]: Virion {ECO:0000269\|PubMed:28290554}.
Subcellular location:		[E(rns) glycoprotein]: Host cell membrane {ECO:0000269\|PubMed:28290554}; Peripheral membrane protein. Virion membrane {ECO:0000269\|PubMed:28290554}; Peripheral membrane protein {ECO:0000305}. Note=The C-terminus membrane anchor of Erns represents an amphipathic helix embedded in plane into the membrane.
Subcellular location:		[Envelope glycoprotein E2]: Host cell surface {ECO:0000269\|PubMed:28290554}. Virion membrane {ECO:0000269\|PubMed:28290554}.
Subcellular location:		[Cysteine protease NS2]: Host membrane {ECO:0000255\|PROSITE-ProRule:PRU01029}; Multi-pass membrane protein {ECO:0000255\|PROSITE-ProRule:PRU01029}.
Subcellular location:		[Serine protease NS3]: Host cytoplasm {ECO:0000269\|PubMed:28848503}.
Subcellular location:		[Non-structural protein 4B]: Host cytoplasm {ECO:0000269\|PubMed:28848503, ECO:0000269\|PubMed:29844394}.
Subcellular location:		[Non-structural protein 5A]: Host cytoplasm {ECO:0000269\|PubMed:28848503}.
Induction:		Translated cap independently from an internal ribosome entry site (IRES). {ECO:0000269\|PubMed:9573242}.
Ptm:		[E(rns) glycoprotein]: Heavily glycosylated. {ECO:0000269\|PubMed:1870198}.
Ptm:		The viral RNA of pestiviruses is expressed as a single polyprotein which undergoes post-translational proteolytic processing resulting in the production of at least eleven individual proteins. The N-terminal protease cleaves itself from the nascent polyprotein autocatalytically and thereby generates the N-terminus of the adjacent viral capsid protein C. {ECO:0000269\|PubMed:8230432, ECO:0000269\|PubMed:8388499}.
Ptm:		[Genome polyprotein]: Cleavage between E2 and p7 is partial.
Similarity:		Belongs to the pestivirus polyprotein family. {ECO:0000305}.