P0C6U9 (R1A_CVM2) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 37. History...
Names and origin
|Protein names||Recommended name:|
Replicase polyprotein 1a
Cleaved into the following 11 chains:
|Organism||Murine coronavirus (strain 2) (MHV-2) (Murine hepatitis virus)|
|Taxonomic identifier||76344 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Betacoronavirus ›|
|Virus host||Mus musculus (Mouse) [TaxID: 10090]|
|Sequence length||4416 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Inferred from homology|
General annotation (Comments)
The papain-like proteinase 1 (PL1-PRO) and papain-like proteinase 2 (PL2-PRO) 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. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent 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.
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.
Non-structural protein 1: binds to the 40S ribosomal subunit and inhibits host translation. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response By similarity.
TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position.
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).
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.
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 Macro domain.
Contains 2 peptidase C16 domains.
Contains 1 peptidase C30 domain.
|This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]|
|Isoform Replicase polyprotein 1a (identifier: P0C6U9-1) |
Also known as: pp1a; ORF1a polyprotein;
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 conventional translation.|
|Isoform Replicase polyprotein 1ab (identifier: P0C6X8-1) |
Also known as: pp1ab;
The sequence of this isoform can be found in the external entry P0C6X8.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 4416||4416||Replicase polyprotein 1a||PRO_0000338266|
|Chain||1 – 247||247||Non-structural protein 1 By similarity||PRO_0000338267|
|Chain||248 – 832||585||Non-structural protein 2 By similarity||PRO_0000338268|
|Chain||833 – 2783||1951||Non-structural protein 3 By similarity||PRO_0000338269|
|Chain||2784 – 3279||496||Non-structural protein 4 By similarity||PRO_0000338270|
|Chain||3280 – 3582||303||3C-like proteinase By similarity||PRO_0000338271|
|Chain||3583 – 3869||287||Non-structural protein 6 By similarity||PRO_0000338272|
|Chain||3870 – 3961||92||Non-structural protein 7 By similarity||PRO_0000338273|
|Chain||3962 – 4155||194||Non-structural protein 8 By similarity||PRO_0000338274|
|Chain||4156 – 4265||110||Non-structural protein 9 By similarity||PRO_0000338275|
|Chain||4266 – 4402||137||Non-structural protein 10 By similarity||PRO_0000338276|
|Chain||4403 – 4416||14||Non-structural protein 11 Potential||PRO_0000338277|
|Transmembrane||2232 – 2252||21||Helical; Potential|
|Transmembrane||2260 – 2280||21||Helical; Potential|
|Transmembrane||2346 – 2366||21||Helical; Potential|
|Transmembrane||2388 – 2408||21||Helical; Potential|
|Transmembrane||2789 – 2809||21||Helical; Potential|
|Transmembrane||2869 – 2889||21||Helical; Potential|
|Transmembrane||3042 – 3062||21||Helical; Potential|
|Transmembrane||3064 – 3084||21||Helical; Potential|
|Transmembrane||3096 – 3116||21||Helical; Potential|
|Transmembrane||3123 – 3143||21||Helical; Potential|
|Transmembrane||3148 – 3168||21||Helical; Potential|
|Transmembrane||3591 – 3611||21||Helical; Potential|
|Transmembrane||3621 – 3641||21||Helical; Potential|
|Transmembrane||3647 – 3667||21||Helical; Potential|
|Transmembrane||3690 – 3710||21||Helical; Potential|
|Transmembrane||3717 – 3737||21||Helical; Potential|
|Transmembrane||3744 – 3764||21||Helical; Potential|
|Transmembrane||3788 – 3808||21||Helical; Potential|
|Domain||1031 – 1268||238||Peptidase C16 1|
|Domain||1269 – 1429||161||Macro|
|Domain||1625 – 1884||260||Peptidase C16 2|
|Domain||3280 – 3582||303||Peptidase C30|
|Zinc finger||1145 – 1173||29||C4-type 1|
|Zinc finger||1741 – 1777||37||C4-type 2|
|Zinc finger||4339 – 4355||17||By similarity|
|Zinc finger||4381 – 4394||14||By similarity|
|Region||2232 – 2408||177||HD1|
|Region||2789 – 3168||380||HD2|
|Region||3525 – 3808||284||HD3|
|Active site||1068||1||For PL1-PRO activity By similarity|
|Active site||1219||1||For PL1-PRO activity By similarity|
|Active site||1663||1||For PL2-PRO activity By similarity|
|Active site||1820||1||For PL2-PRO activity By similarity|
|Active site||3320||1||For 3CL-PRO activity By similarity|
|Active site||3424||1||For 3CL-PRO activity By similarity|
|Site||247 – 248||2||Cleavage; by PL1-PRO By similarity|
|Site||832 – 833||2||Cleavage; by PL1-PRO By similarity|
|Site||2783 – 2784||2||Cleavage; by PL2-PRO By similarity|
|Site||3279 – 3280||2||Cleavage; by 3CL-PRO By similarity|
|Site||3582 – 3583||2||Cleavage; by 3CL-PRO By similarity|
|Site||3869 – 3870||2||Cleavage; by 3CL-PRO By similarity|
|Site||3961 – 3962||2||Cleavage; by 3CL-PRO By similarity|
|Site||4155 – 4156||2||Cleavage; by 3CL-PRO By similarity|
|Site||4265 – 4266||2||Cleavage; by 3CL-PRO By similarity|
|Site||4402 – 4403||2||Cleavage; by 3CL-PRO By similarity|
|||"Pathogenesis and sequence analysis of mouse hepatitis virus type 2: an experimental model system of acute meningitis and hepatitis in mice."|
Das Sarma J., Hingley S.T., Lai M.M.C., Weiss S.R., Lavi E.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|AF201929 Genomic RNA. Translation: AAF19383.1.|
3D structure databases
|SMR||P0C6U9. Positions 3997-4147, 4271-4395. |
Protocols and materials databases
Family and domain databases
|InterPro||IPR022570. Coronavirus_NSP1. |
|Pfam||PF11963. DUF3477. 1 hit. |
PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF08715. Viral_protease. 1 hit.
|SMART||SM00506. A1pp. 1 hit. |
|SUPFAM||SSF101816. SSF101816. 1 hit. |
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
|PROSITE||PS51442. M_PRO. 1 hit. |
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
|Accession||Primary (citable) accession number: P0C6U9|
Secondary accession number(s): Q9PYA3
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|