P0C6Y4 (R1AB_PEDV7) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 46. History...
Names and origin
|Protein names||Recommended name:|
Replicase polyprotein 1ab
Cleaved into the following 15 chains:
|Organism||Porcine epidemic diarrhea virus (strain CV777) (PEDV) [Complete proteome]|
|Taxonomic identifier||229032 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Alphacoronavirus ›|
|Virus host||Sus scrofa (Pig) [TaxID: 9823]|
|Sequence length||6781 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Inferred from homology|
General annotation (Comments)
The replicase polyprotein of coronaviruses 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.
The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 By similarity.
The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function By similarity.
The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) By similarity.
The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction By similarity.
Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter By similarity.
Nsp9 is a ssRNA-binding protein By similarity.
NendoU is a Mn2+-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond By similarity.
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).
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
ATP + H2O = ADP + phosphate.
3CL-PRO exists as monomer and homodimer. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer. Nsp9 is a dimer. Nsp10 forms a dodecamer By similarity.
Non-structural protein 7: Host cytoplasm › host perinuclear region By similarity. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Non-structural protein 8: Host cytoplasm › host perinuclear region By similarity. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Non-structural protein 9: Host cytoplasm › host perinuclear region By similarity. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Non-structural protein 10: Host cytoplasm › host perinuclear region By similarity. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes By similarity.
Helicase: Host endoplasmic reticulum-Golgi intermediate compartment Potential. Note: The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA By similarity.
The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.
Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed By similarity.
Belongs to the coronaviruses polyprotein 1ab family.
Contains 1 (+)RNA virus helicase ATP-binding domain.
Contains 1 (+)RNA virus helicase C-terminal domain.
Contains 1 CV MBD (coronavirus metal-binding) domain.
Contains 1 Macro domain.
Contains 2 peptidase C16 domains.
Contains 1 peptidase C30 domain.
Contains 1 RdRp catalytic domain.
The sequence AAK38661.1 differs from that shown. Reason: Erroneous gene model prediction.
|This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]|
|Isoform Replicase polyprotein 1ab (identifier: P0C6Y4-1) |
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: P0C6V6-1) |
Also known as: pp1a; ORF1a polyprotein;
The sequence of this isoform can be found in the external entry P0C6V6.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by conventional translation.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 110||110||Non-structural protein 1 By similarity||PRO_0000037369|
|Chain||111 – 895||785||Non-structural protein 2 By similarity||PRO_0000037370|
|Chain||896 – 2516||1621||Non-structural protein 3 By similarity||PRO_0000037371|
|Chain||2517 – 2997||481||Non-structural protein 4 By similarity||PRO_0000037372|
|Chain||2998 – 3299||302||3C-like proteinase By similarity||PRO_0000037373|
|Chain||3300 – 3579||280||Non-structural protein 6 By similarity||PRO_0000037374|
|Chain||3580 – 3662||83||Non-structural protein 7 By similarity||PRO_0000037375|
|Chain||3663 – 3857||195||Non-structural protein 8 By similarity||PRO_0000037376|
|Chain||3858 – 3965||108||Non-structural protein 9 By similarity||PRO_0000037377|
|Chain||3966 – 4100||135||Non-structural protein 10 By similarity||PRO_0000037378|
|Chain||4101 – 5027||927||RNA-directed RNA polymerase By similarity||PRO_0000037379|
|Chain||5028 – 5546||519||Helicase||PRO_0000037380|
|Chain||5547 – 6141||595||Exoribonuclease By similarity||PRO_0000037381|
|Chain||6142 – 6480||339||Uridylate-specific endoribonuclease By similarity||PRO_0000037382|
|Chain||6481 – 6781||301||Putative 2'-O-methyl transferase By similarity||PRO_0000037383|
|Transmembrane||1959 – 1979||21||Helical; Potential|
|Transmembrane||2022 – 2042||21||Helical; Potential|
|Transmembrane||2105 – 2125||21||Helical; Potential|
|Transmembrane||2127 – 2147||21||Helical; Potential|
|Transmembrane||2150 – 2170||21||Helical; Potential|
|Transmembrane||2528 – 2548||21||Helical; Potential|
|Transmembrane||2619 – 2639||21||Helical; Potential|
|Transmembrane||2654 – 2674||21||Helical; Potential|
|Transmembrane||2754 – 2774||21||Helical; Potential|
|Transmembrane||2787 – 2807||21||Helical; Potential|
|Transmembrane||2814 – 2834||21||Helical; Potential|
|Transmembrane||2863 – 2883||21||Helical; Potential|
|Transmembrane||3336 – 3356||21||Helical; Potential|
|Transmembrane||3361 – 3381||21||Helical; Potential|
|Transmembrane||3399 – 3419||21||Helical; Potential|
|Transmembrane||3431 – 3451||21||Helical; Potential|
|Transmembrane||3454 – 3474||21||Helical; Potential|
|Transmembrane||3476 – 3496||21||Helical; Potential|
|Transmembrane||3500 – 3520||21||Helical; Potential|
|Domain||1057 – 1296||240||Peptidase C16 1|
|Domain||1297 – 1465||169||Macro|
|Domain||1691 – 1951||261||Peptidase C16 2|
|Domain||2998 – 3299||302||Peptidase C30|
|Domain||4707 – 4869||163||RdRp catalytic|
|Domain||5028 – 5111||84||CV MBD|
|Domain||5275 – 5466||192||(+)RNA virus helicase ATP-binding|
|Domain||5467 – 5636||170||(+)RNA virus helicase C-terminal|
|Zinc finger||1162 – 1193||32||C4-type|
|Zinc finger||4039 – 4055||17||By similarity|
|Zinc finger||4081 – 4094||14||By similarity|
|Nucleotide binding||5310 – 5317||8||ATP By similarity|
|Region||1959 – 2170||212||HD1|
|Region||2528 – 2883||356||HD2|
|Region||3336 – 3520||185||HD3|
|Compositional bias||1816 – 1932||117||Val-rich|
|Active site||1091||1||For PL1-PRO activity By similarity|
|Active site||1239||1||For PL1-PRO activity By similarity|
|Active site||1729||1||For PL2-PRO activity By similarity|
|Active site||1888||1||For PL2-PRO activity By similarity|
|Active site||3038||1||For 3CL-PRO activity By similarity|
|Active site||3141||1||For 3CL-PRO activity By similarity|
|Site||110 – 111||2||Cleavage; by PL1-PRO By similarity|
|Site||895 – 896||2||Cleavage; by PL1-PRO By similarity|
|Site||2516 – 2517||2||Cleavage; by PL2-PRO By similarity|
|Site||2997 – 2998||2||Cleavage; by 3CL-PRO By similarity|
|Site||3299 – 3300||2||Cleavage; by 3CL-PRO By similarity|
|Site||3579 – 3580||2||Cleavage; by 3CL-PRO By similarity|
|Site||3662 – 3663||2||Cleavage; by 3CL-PRO By similarity|
|Site||3857 – 3858||2||Cleavage; by 3CL-PRO By similarity|
|Site||3965 – 3966||2||Cleavage; by 3CL-PRO By similarity|
|Site||4100 – 4101||2||Cleavage; by 3CL-PRO By similarity|
|Site||5027 – 5028||2||Cleavage; by 3CL-PRO By similarity|
|Site||5546 – 5547||2||Cleavage; by 3CL-PRO By similarity|
|Site||6141 – 6142||2||Cleavage; by 3CL-PRO By similarity|
|Site||6480 – 6481||2||Cleavage; by 3CL-PRO By similarity|
|||"Further analysis of the genome of porcine epidemic diarrhea virus."|
Bridgen A., Kocherhans R., Tobler K., Carvajal A., Ackermann M.
Adv. Exp. Med. Biol. 440:781-786(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence."|
Kocherhans R., Bridgen A., Ackermann M., Tobler K.
Virus Genes 23:137-144(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|AF353511 Genomic RNA. Translation: AAK38661.1. Sequence problems.|
|RefSeq||NP_598309.2. NC_003436.1. |
3D structure databases
|SMR||P0C6Y4. Positions 2998-3297, 3860-3964, 3972-4096. |
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR027351. (+)RNA_virus_helicase_core_dom. |
|Pfam||PF06478. Corona_RPol_N. 1 hit. |
PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF06471. NSP11. 1 hit.
PF06460. NSP13. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF00680. RdRP_1. 1 hit.
PF01443. Viral_helicase1. 1 hit.
PF08715. Viral_protease. 2 hits.
|SMART||SM00506. A1pp. 1 hit. |
|SUPFAM||SSF101816. SSF101816. 1 hit. |
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF51126. SSF51126. 1 hit.
SSF52540. SSF52540. 1 hit.
|PROSITE||PS51653. CV_MBD. 1 hit. |
PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
PS51657. PSRV_HELICASE. 1 hit.
|Accession||Primary (citable) accession number: P0C6Y4|
Secondary accession number(s): Q91AV2
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|