Q04561 (RPOA_PRRSL) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 111. History...
Names and origin
|Sequence length||3855 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
The replicase polyprotein 1ab is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
Nsp1 is essential for viral subgenomic mRNA synthesis By similarity.
Nsp1-alpha inhibits IFN-beta production. Counteracts the action of NF-kappaB by decreasing the phosphorylation of IkappaB-alpha, such that the degradation of IkappaB-alpha is suppressed. This leads to the blockage of NF-kappaB nuclear translocation and thus interference of NF-kappaB activation. Also seems to inhibit IRF3-dependent pathways By similarity.
Nsp2 cysteine proteinase which cleaves the nsp2/nsp3 site in the polyprotein. Also displays deubiquitinating and deISGylase activities. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent host innate immunity. Deubiquitinates host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation By similarity.
The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein By similarity.
The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity By similarity.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
ATP + H2O = ADP + phosphate.
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane By similarity.
The OTU-like region is responsible for the deubiquitinating and deISGylation activities of Nsp2 By similarity.
Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. Nsp1 is autocleaved into two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative pathways for processing. Either nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and nsp6-7 are processed, which represents the minor pathway. The major pathway occurs when nsp2 acts as cofactor for nsp4 By similarity.
Belongs to the arteriviridae polyprotein family.
Contains 1 (+)RNA virus helicase ATP-binding domain.
Contains 1 (+)RNA virus helicase C-terminal domain.
Contains 1 AV MBD (arterivirus metal-binding) domain.
Contains 1 peptidase C31 domain.
Contains 1 peptidase C32 domain.
Contains 1 peptidase C33 domain.
Contains 1 peptidase S32 domain.
Contains 1 RdRp catalytic domain.
The sequence AAA46273.2 differs from that shown. Reason: Erroneous initiation.
The sequence AAA46274.1 differs from that shown. Reason: Erroneous initiation.
|Biological process||Host-virus interaction|
Inhibition of host innate immune response by virus
Inhibition of host interferon signaling pathway by virus
Inhibition of host ISG15 by virus
Inhibition of host NF-kappa-B by virus
Inhibition of host STAT1 by virus
Modulation of host ubiquitin pathway by viral deubiquitinase
Modulation of host ubiquitin pathway by virus
Viral RNA replication
|Cellular component||Host cytoplasm|
|Coding sequence diversity||Ribosomal frameshifting|
RNA-directed RNA polymerase
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||modulation by virus of host protein ubiquitination|
Inferred from electronic annotation. Source: UniProtKB-KWproteolysis
Inferred from electronic annotation. Source: UniProtKB-KWsuppression by virus of host ISG15 activity
Inferred from electronic annotation. Source: UniProtKB-KWsuppression by virus of host NF-kappaB transcription factor activity
Inferred from electronic annotation. Source: UniProtKB-KWsuppression by virus of host STAT1 activity
Inferred from electronic annotation. Source: UniProtKB-KWsuppression by virus of host type I interferon-mediated signaling pathway
Inferred from electronic annotation. Source: UniProtKB-KWtranscription, DNA-templated
Inferred from electronic annotation. Source: InterProviral RNA genome replication
Inferred from electronic annotation. Source: InterProviral protein processing
Inferred from electronic annotation. Source: InterPro
|Cellular_component||host cell membrane|
Inferred from electronic annotation. Source: UniProtKB-SubCellhost cell nucleus
Inferred from electronic annotation. Source: UniProtKB-SubCellhost cell perinuclear region of cytoplasm
Inferred from electronic annotation. Source: UniProtKB-SubCellintegral component of membrane
Inferred from electronic annotation. Source: UniProtKB-KW
Inferred from electronic annotation. Source: UniProtKB-KWRNA binding
Inferred from electronic annotation. Source: InterProRNA-directed RNA polymerase activity
Inferred from electronic annotation. Source: UniProtKB-KWcysteine-type endopeptidase activity
Inferred from electronic annotation. Source: InterProhelicase activity
Inferred from electronic annotation. Source: UniProtKB-KWmetal ion binding
Inferred from electronic annotation. Source: UniProtKB-KWserine-type endopeptidase activity
Inferred from electronic annotation. Source: InterPro
|Complete GO annotation...|
|This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]|
|Isoform Replicase polyprotein 1ab (identifier: Q04561-1) |
Also known as: pp1ab;
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Note: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.|
|Isoform Replicase polyprotein 1a (identifier: Q04561-2) |
Also known as: pp1a; ORF1a polyprotein;
The sequence of this isoform differs from the canonical sequence as follows:
|Note: Produced by conventional translation.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 3855||3855||Replicase polyprotein 1ab||PRO_0000036683|
|Chain||1 – 384||384||Nsp1 By similarity||PRO_0000410828|
|Chain||1 – 180||180||Nsp1-alpha papain-like cysteine proteinase Potential||PRO_0000036685|
|Chain||181 – 385||205||Nsp1-beta papain-like cysteine proteinase Potential||PRO_0000036686|
|Chain||386 – 1463||1078||Nsp2 cysteine proteinase Potential||PRO_0000036687|
|Chain||1464 – 1693||230||Non-structural protein 3 By similarity||PRO_0000036688|
|Chain||1694 – 1896||203||3C-like serine proteinase By similarity||PRO_0000036689|
|Chain||1897 – 2351||455||Non-structural protein 5-6-7 By similarity||PRO_0000036690|
|Chain||1897 – 2066||170||Non-structural protein 5 By similarity||PRO_0000423126|
|Chain||2067 – 2082||16||Non-structural protein 6 By similarity||PRO_0000423127|
|Chain||2083 – 2231||149||Non-structural protein 7-alpha By similarity||PRO_0000423128|
|Chain||2232 – 2351||120||Non-structural protein 7-beta By similarity||PRO_0000423129|
|Chain||2352 – 3037||686||RNA-directed RNA polymerase By similarity||PRO_0000036691|
|Chain||2352 – 2396||45||Non-structural protein 8 By similarity||PRO_0000036692|
|Chain||3038 – 3479||442||Helicase By similarity||PRO_0000036693|
|Chain||3480 – 3703||224||Non-structural protein 11 By similarity||PRO_0000036694|
|Chain||3704 – 3855||152||Non-structural protein 12 By similarity||PRO_0000036695|
|Transmembrane||1134 – 1154||21||Helical; Potential|
|Transmembrane||1179 – 1199||21||Helical; Potential|
|Transmembrane||1252 – 1272||21||Helical; Potential|
|Transmembrane||1468 – 1488||21||Helical; Potential|
|Transmembrane||1521 – 1541||21||Helical; Potential|
|Transmembrane||1543 – 1563||21||Helical; Potential|
|Transmembrane||1573 – 1593||21||Helical; Potential|
|Transmembrane||1609 – 1629||21||Helical; Potential|
|Transmembrane||1919 – 1939||21||Helical; Potential|
|Transmembrane||1943 – 1963||21||Helical; Potential|
|Transmembrane||1977 – 1997||21||Helical; Potential|
|Transmembrane||2020 – 2040||21||Helical; Potential|
|Domain||69 – 180||112||Peptidase C31|
|Domain||269 – 385||117||Peptidase C32|
|Domain||420 – 527||108||Peptidase C33|
|Domain||1694 – 1896||203||Peptidase S32|
|Domain||2783 – 2917||135||RdRp catalytic|
|Domain||3038 – 3101||64||AV MBD|
|Domain||3151 – 3310||160||(+)RNA virus helicase ATP-binding|
|Domain||3311 – 3440||130||(+)RNA virus helicase C-terminal|
|Zinc finger||8 – 28||21||C4-type; atypical|
|Nucleotide binding||3186 – 3193||8||ATP By similarity|
|Region||69 – 182||114||PCP1-alpha|
|Region||269 – 384||116||PCP1-beta|
|Region||418 – 505||88||OTU-like|
|Region||1149 – 1272||124||HD1|
|Region||1327 – 1351||25||WCCH|
|Region||1468 – 1629||162||HD2|
|Region||1919 – 2040||122||HD3|
|Active site||76||1||For Nsp1-alpha papain-like cysteine proteinase activity Ref.4|
|Active site||146||1||For Nsp1-alpha papain-like cysteine proteinase activity Ref.4|
|Active site||276||1||For Nsp1-beta papain-like cysteine proteinase activity Ref.4|
|Active site||345||1||For Nsp1-beta papain-like cysteine proteinase activity Ref.4|
|Active site||429||1||For Nsp2 cysteine proteinase activity By similarity|
|Active site||498||1||For Nsp2 cysteine proteinase activity By similarity|
|Active site||1732||1||Charge relay system; for 3C-like serine proteinase activity By similarity|
|Active site||1757||1||Charge relay system; for 3C-like serine proteinase activity By similarity|
|Active site||1810||1||Charge relay system; for 3C-like serine proteinase activity By similarity|
|Site||180 – 181||2||Cleavage; by autolysis Potential|
|Site||385 – 386||2||Cleavage; by autolysis By similarity|
|Site||1463 – 1464||2||Cleavage; by CP2 Potential|
|Site||1693 – 1694||2||Cleavage; by 3CLSP By similarity|
|Site||1896 – 1897||2||Cleavage; by 3CLSP By similarity|
|Site||2066 – 2067||2||Cleavage; by 3CLSP By similarity|
|Site||2082 – 2083||2||Cleavage; by 3CLSP By similarity|
|Site||2231 – 2232||2||Cleavage; by 3CLSP By similarity|
|Site||2351 – 2352||2||Cleavage; by 3CLSP By similarity|
|Site||3037 – 3038||2||Cleavage; by 3CLSP By similarity|
|Site||3088||1||Involved in mRNA transcription process By similarity|
|Site||3479 – 3480||2||Cleavage; by 3CLSP By similarity|
|Site||3703 – 3704||2||Cleavage; by 3CLSP By similarity|
|Alternative sequence||2397 – 3855||1459||Missing in isoform Replicase polyprotein 1a.||VSP_032892|
|Mutagenesis||76||1||C → G or S: Complete loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||92||1||H → F or Y: No effect. Ref.4|
|Mutagenesis||115||1||H → A: No effect. Ref.4|
|Mutagenesis||115||1||H → Y: 50% loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||146||1||H → D, F, I, N or Y: Complete loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||157||1||H → D: 20% loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||157||1||H → I: 90% loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||157||1||H → N: 50% loss of cleavage between nsp1-alpha and nsp1-beta. Ref.4|
|Mutagenesis||157||1||H → Y: No effect. Ref.4|
|Mutagenesis||276||1||C → I, L, R or S: Complete loss of cleavage between nsp1-beta and nsp2. Ref.4|
|Mutagenesis||345||1||H → D or Y: Complete loss of cleavage between nsp1-beta and nsp2. Ref.4|
|Sequence conflict||3502||1||T → V in AAA47101. Ref.3|
|Sequence conflict||3740||1||V → I in AAA47101. Ref.3|
|||"Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV."|
Meulenberg J.J.M., Hulst M.M., de Meijer E.J., Moonen P.L.J.M., den Besten A., de Kluyver E.P., Wensvoort G., Moormann R.J.M.
Virology 192:62-72(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||Kroese M.V., Moormann R.J.M.|
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 3327.
|||"Molecular characterization of porcine reproductive and respiratory syndrome virus, a member of the arterivirus group."|
Conzelmann K.K., Visser N., van Woensel P., Thiel H.J.
Virology 193:329-339(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 3323-3855.
Strain: Isolate Boxmeer 10.
|||"Processing and evolution of the N-terminal region of the arterivirus replicase ORF1a protein: identification of two papainlike cysteine proteases."|
den Boon J.A., Faaberg K.S., Meulenberg J.J.M., Wassenaar A.L.M., Plagemann P.G.W., Gorbalenya A.E., Snijder E.J.
J. Virol. 69:4500-4505(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITES OF PCP1-ALPHA AND PCP1-BETA, MUTAGENESIS OF CYS-76; HIS-92; HIS-115; HIS-146; HIS-157; HIS-157; CYS-276 AND HIS-345.
|M96262 Genomic RNA. Translation: AAA46273.2. Different initiation.|
M96262 Genomic RNA. Translation: AAA46274.1. Different initiation.
L04493 Genomic RNA. Translation: AAA47101.1.
3D structure databases
Protein family/group databases
Protocols and materials databases
Family and domain databases
|Gene3D||18.104.22.1680. 1 hit. |
|InterPro||IPR027351. (+)RNA_virus_helicase_core_dom. |
|Pfam||PF05410. Peptidase_C31. 1 hit. |
PF05411. Peptidase_C32. 1 hit.
PF05412. Peptidase_C33. 1 hit.
PF05579. Peptidase_S32. 1 hit.
PF00680. RdRP_1. 1 hit.
PF01443. Viral_helicase1. 1 hit.
|SUPFAM||SSF50494. SSF50494. 1 hit. |
SSF52540. SSF52540. 1 hit.
|PROSITE||PS51538. AV_CP. 1 hit. |
PS51652. AV_MBD. 1 hit.
PS51493. AV_NSP4_PRO. 1 hit.
PS51539. AV_PCP_ALPHA. 1 hit.
PS51540. AV_PCP_BETA. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
|Accession||Primary (citable) accession number: Q04561|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|