A0MD28 (RPOA_PRRSS) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 31.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
Protein attributes
| Sequence length | 3838 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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 By similarity. Ref.3 Nsp1 is essential for viral subgenomic mRNA synthesis By similarity. Ref.3 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. Ref.3 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 By similarity. Deubiquitinates host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation. Ref.3 The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein By similarity. Ref.3 The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity By similarity. Ref.3 |
| Catalytic activity | 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). |
| Subcellular location | Nsp1: Host nucleus By similarity. Host cytoplasm By similarity. Nsp1-alpha papain-like cysteine proteinase: Host nucleus By similarity. Host cytoplasm By similarity. Nsp1-beta papain-like cysteine proteinase: Host cytoplasm By similarity. Nsp2 cysteine proteinase: Host membrane; Multi-pass membrane protein Potential. Non-structural protein 3: Host membrane; Multi-pass membrane protein Potential. Non-structural protein 5-6-7: Host membrane; Multi-pass membrane protein Potential. 3C-like serine proteinase: Host cytoplasm Potential. RNA-directed RNA polymerase: Host cytoplasm › host perinuclear region Potential. Helicase: Host cytoplasm › host perinuclear region Potential. |
| Domain | 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 Probable. |
| Post-translational modification | 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. |
| Sequence similarities | 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. |
| Sequence caution | The sequence AAR37017.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select] | ||||||
| Isoform Replicase polyprotein 1ab (identifier: A0MD28-1) 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: A0MD28-2) Also known as: pp1a; ORF1a polyprotein; The sequence of this isoform differs from the canonical sequence as follows: 2380-3838: Missing. | ||||||
| Note: Produced by conventional translation. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 3838 | 3838 | Replicase polyprotein 1ab By similarity | PRO_0000397084 | |||||
| Chain | 1 – 384 | 384 | Nsp1 By similarity | PRO_0000410830 | |||||
| Chain | 1 – 180 | 180 | Nsp1-alpha papain-like cysteine proteinase Potential | PRO_0000397085 | |||||
| Chain | 181 – 385 | 205 | Nsp1-beta papain-like cysteine proteinase Potential | PRO_0000397086 | |||||
| Chain | 386 – 1446 | 1061 | Nsp2 cysteine proteinase By similarity | PRO_0000397087 | |||||
| Chain | 1447 – 1676 | 230 | Non-structural protein 3 By similarity | PRO_0000397088 | |||||
| Chain | 1677 – 1879 | 203 | 3C-like serine proteinase By similarity | PRO_0000397089 | |||||
| Chain | 1880 – 2334 | 455 | Non-structural protein 5-6-7 By similarity | PRO_0000397090 | |||||
| Chain | 2335 – 3020 | 686 | RNA-directed RNA polymerase By similarity | PRO_0000397091 | |||||
| Chain | 2335 – 2379 | 45 | Non-structural protein 8 By similarity | PRO_0000397092 | |||||
| Chain | 3021 – 3462 | 442 | Helicase By similarity | PRO_0000397093 | |||||
| Chain | 3463 – 3686 | 224 | Non-structural protein 11 By similarity | PRO_0000397094 | |||||
| Chain | 3687 – 3838 | 152 | Non-structural protein 12 By similarity | PRO_0000397095 | |||||
Regions | |||||||||
| Transmembrane | 1094 – 1114 | 21 | Helical; Potential | ||||||
| Transmembrane | 1117 – 1137 | 21 | Helical; Potential | ||||||
| Transmembrane | 1162 – 1182 | 21 | Helical; Potential | ||||||
| Transmembrane | 1211 – 1231 | 21 | Helical; Potential | ||||||
| Transmembrane | 1235 – 1255 | 21 | Helical; Potential | ||||||
| Transmembrane | 1450 – 1470 | 21 | Helical; Potential | ||||||
| Transmembrane | 1526 – 1546 | 21 | Helical; Potential | ||||||
| Transmembrane | 1556 – 1576 | 21 | Helical; Potential | ||||||
| Transmembrane | 1592 – 1612 | 21 | Helical; Potential | ||||||
| Transmembrane | 1875 – 1895 | 21 | Helical; Potential | ||||||
| Transmembrane | 1916 – 1936 | 21 | Helical; Potential | ||||||
| Transmembrane | 1960 – 1980 | 21 | Helical; Potential | ||||||
| Transmembrane | 2003 – 2023 | 21 | Helical; Potential | ||||||
| Transmembrane | 2029 – 2048 | 20 | Helical; Potential | ||||||
| Domain | 69 – 180 | 112 | Peptidase C31 | ||||||
| Domain | 269 – 385 | 117 | Peptidase C32 | ||||||
| Domain | 420 – 527 | 108 | Peptidase C33 | ||||||
| Domain | 1677 – 1879 | 203 | Peptidase S32 | ||||||
| Domain | 2765 – 2899 | 135 | RdRp catalytic | ||||||
| Domain | 3021 – 3084 | 64 | AV MBD | ||||||
| Domain | 3134 – 3293 | 160 | (+)RNA virus helicase ATP-binding | ||||||
| Domain | 3294 – 3423 | 130 | (+)RNA virus helicase C-terminal | ||||||
| Zinc finger | 8 – 28 | 21 | C4-type; atypical | ||||||
| Nucleotide binding | 3168 – 3175 | 8 | ATP By similarity | ||||||
| Region | 69 – 182 | 114 | PCP1-alpha By similarity | ||||||
| Region | 269 – 384 | 116 | PCP1-beta By similarity | ||||||
| Region | 418 – 505 | 88 | OTU-like | ||||||
| Region | 1132 – 1255 | 124 | HD1 By similarity | ||||||
| Region | 1310 – 1334 | 25 | WCCH By similarity | ||||||
| Region | 1451 – 1612 | 162 | HD2 By similarity | ||||||
| Region | 1902 – 2023 | 122 | HD3 By similarity | ||||||
Sites | |||||||||
| Active site | 76 | 1 | For Nsp1-alpha papain-like cysteine proteinase activity By similarity | ||||||
| Active site | 146 | 1 | For Nsp1-alpha papain-like cysteine proteinase activity By similarity | ||||||
| Active site | 276 | 1 | For Nsp1-beta papain-like cysteine proteinase activity By similarity | ||||||
| Active site | 345 | 1 | For Nsp1-beta papain-like cysteine proteinase activity By similarity | ||||||
| Active site | 429 | 1 | For Nsp2 cysteine proteinase activity By similarity | ||||||
| Active site | 498 | 1 | For Nsp2 cysteine proteinase activity By similarity | ||||||
| Active site | 1715 | 1 | Charge relay system; for 3C-like serine proteinase activity By similarity | ||||||
| Active site | 1740 | 1 | Charge relay system; for 3C-like serine proteinase activity By similarity | ||||||
| Active site | 1793 | 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 | 1446 – 1447 | 2 | Cleavage; by CP2 Potential | ||||||
| Site | 1676 – 1677 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 1879 – 1880 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 2049 – 2050 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 2065 – 2066 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 2334 – 2335 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 3020 – 3021 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 3071 | 1 | Involved in mRNA transcription process By similarity | ||||||
| Site | 3462 – 3463 | 2 | Cleavage; by 3CLSP By similarity | ||||||
| Site | 3686 – 3687 | 2 | Cleavage; by 3CLSP By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 2380 – 3838 | 1459 | Missing in isoform Replicase polyprotein 1a. | VSP_039634 | |||||
| Natural variant | 666 | 1 | R → Q in strain: Infectious clone SD 01-08. | ||||||
| Natural variant | 1005 | 1 | R → K in strain: Infectious clone SD 01-08. | ||||||
| Natural variant | 1012 | 1 | N → S in strain: Infectious clone SD 01-08. | ||||||
| Natural variant | 3092 | 1 | P → L in strain: Infectious clone SD 01-08. | ||||||
| Natural variant | 3682 | 1 | Y → H in strain: Infectious clone SD 01-08. | ||||||
Experimental info | |||||||||
| Mutagenesis | 429 | 1 | C → A: Lethal. Ref.3 | ||||||
| Mutagenesis | 458 | 1 | D → A: Slight reduction in the ability of Nsp2 to impair NF-kappaB activation. Ref.3 | ||||||
| Mutagenesis | 462 | 1 | S → A: Reduction in the ability of Nsp2 to impair NF-kappaB activation. Ref.3 | ||||||
| Mutagenesis | 463 | 1 | D → A: Lethal. Ref.3 | ||||||
| Mutagenesis | 465 | 1 | D → A: Reduction in the ability of Nsp2 to impair NF-kappaB activation. Ref.3 | ||||||
| Mutagenesis | 498 | 1 | H → A: Lethal. Ref.3 | ||||||
Sequences
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References
| [1] | "Heterogeneity in Nsp2 of European-like porcine reproductive and respiratory syndrome viruses isolated in the United States." Fang Y., Kim D.Y., Ropp S., Steen P., Christopher-Hennings J., Nelson E.A., Rowland R.R. Virus Res. 100:229-235(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. |
| [2] | "A full-length cDNA infectious clone of North American type 1 porcine reproductive and respiratory syndrome virus: expression of green fluorescent protein in the Nsp2 region." Fang Y., Rowland R.R., Roof M., Lunney J.K., Christopher-Hennings J., Nelson E.A. J. Virol. 80:11447-11455(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Infectious clone SD 01-08. |
| [3] | "The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 possesses deubiquitinating and interferon antagonism functions." Sun Z., Chen Z., Lawson S.R., Fang Y. J. Virol. 84:7832-7846(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF NSP2 IN DEUBIQUITINATION, MUTAGENESIS OF CYS-429; ASP-458; SER-462; ASP-463; ASP-465 AND HIS-498. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY375474 Genomic RNA. Translation: AAR37016.1. AY375474 Genomic RNA. Translation: AAR37017.1. Different initiation. DQ489311 Genomic RNA. Translation: ABF66340.1. DQ489311 Genomic RNA. Translation: ABF66341.1. |
3D structure databases | |
| ModBase | Search... |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Family and domain databases | |
| InterPro | IPR027351. (+)RNA_virus_helicase_core_dom. IPR008743. Arterivirus_Nsp2_C33. IPR023338. Arterivirus_NSP4_peptidase. IPR027355. AV_MBD_dom. IPR008741. AV_PCPalpha. IPR025773. AV_PCPbeta. IPR008760. EAV_peptidase_S32. IPR027417. P-loop_NTPase. IPR001205. RNA-dir_pol_C. IPR007094. RNA-dir_pol_PSvirus. IPR009003. Trypsin-like_Pept_dom. [Graphical view] |
| 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. [Graphical view] |
| SUPFAM | SSF50494. Pept_Ser_Cys. 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. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | RPOA_PRRSS | ||||||||
| Accession | Primary (citable) accession number: A0MD28 Secondary accession number(s): A0MD29, Q6U9W7, Q6U9W8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Viral Protein Annotation Program | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with
