A0A1S5VG80 · A0A1S5VG80_CVHOC

Function

function

Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).
Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.
Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.
Forms a primer, NSP9-pU, which is utilized by the polymerase for the initiation of RNA chains. Interacts with ribosome signal recognition particle RNA (SRP). Together with NSP8, suppress protein integration into the cell membrane, thereby disrupting host immune defenses.
Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.
May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.
Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.
Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.
Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.
Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.
Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.
Plays a role in viral RNA synthesis through two distinct activities. The N7-guanine methyltransferase activity plays a role in the formation of the cap structure GpppA-RNA. The proofreading exoribonuclease reduces the sensitivity of the virus to RNA mutagens during replication. This activity acts on both ssRNA and dsRNA in a 3'-5' direction.
Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR. Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors.
RNA-directed RNA polymerase that catalyzes the transcription of viral genomic and subgenomic RNAs. Acts in complex with nsp7 and nsp8 to transcribe both the minus and positive strands of genomic RNA. The kinase-like NiRAN domain of NSP12 attaches one or more nucleotides to the amino terminus of NSP9, forming a covalent RNA-protein intermediate that serves as transcription/replication primer. Subgenomic RNAs (sgRNAs) are formed by discontinuous transcription: The polymerase has the ability to pause at transcription-regulating sequences (TRS) and jump to the leader TRS, resulting in a major deletion. This creates a series of subgenomic RNAs that are replicated, transcribed and translated. In addition, Nsp12 is a subunit of the viral RNA capping enzyme that catalyzes the RNA guanylyltransferase reaction for genomic and sub-genomic RNAs. Subsequently, the NiRAN domain transfers RNA to GDP, and forms the core cap structure GpppA-RNA.
Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.
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.

Caution

Lacks conserved residue(s) required for the propagation of feature annotation.

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Mn2+ (UniProtKB | Rhea| CHEBI:29035 )

Features

Showing features for active site, binding site.

TypeIDPosition(s)Description
Active site5989
Active site5991
Active site6090
Active site6167
Active site6172
Binding site6230-6236S-adenosyl-L-methionine (UniProtKB | ChEBI)
Active site6684
Active site6699
Active site6739

GO annotations

AspectTerm
Cellular Componenthost cell endoplasmic reticulum-Golgi intermediate compartment
Cellular Componenthost cell membrane
Cellular Componenthost cell perinuclear region of cytoplasm
Cellular Componentmembrane
Molecular Function3'-5'-RNA exonuclease activity
Molecular FunctionATP binding
Molecular Functioncysteine-type deubiquitinase activity
Molecular Functioncysteine-type endopeptidase activity
Molecular Functionendonuclease activity
Molecular Functionlyase activity
Molecular FunctionmRNA (nucleoside-2'-O-)-methyltransferase activity
Molecular FunctionmRNA 5'-cap (guanine-N7-)-methyltransferase activity
Molecular Functionomega peptidase activity
Molecular FunctionRNA helicase activity
Molecular FunctionRNA-dependent RNA polymerase activity
Molecular Functionsingle-stranded RNA binding
Molecular Functionzinc ion binding
Biological ProcessDNA-templated transcription
Biological Processinduction by virus of host autophagy
Biological Processproteolysis
Biological Processsymbiont-mediated degradation of host mRNA
Biological Processsymbiont-mediated perturbation of host ubiquitin-like protein modification
Biological Processsymbiont-mediated suppression of host ISG15-protein conjugation
Biological Processsymbiont-mediated suppression of host NF-kappaB cascade
Biological Processsymbiont-mediated suppression of host type I interferon-mediated signaling pathway
Biological Processviral protein processing
Biological Processviral RNA genome replication
Biological Processviral translational frameshifting
Biological Processvirus-mediated perturbation of host defense response

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    ORF1ab polyprotein

Gene names

    • Name
      orf1ab

Organism names

  • Taxonomic identifier
  • Strain
    • MY-U002/12
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Pisuviricota > Pisoniviricetes > Nidovirales > Cornidovirineae > Coronaviridae > Orthocoronavirinae > Betacoronavirus > Embecovirus > Betacoronavirus 1

Accessions

  • Primary accession
    A0A1S5VG80

Subcellular Location

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane2195-2215Helical
Transmembrane2309-2331Helical
Transmembrane2755-2778Helical
Transmembrane3026-3051Helical
Transmembrane3063-3084Helical
Transmembrane3090-3112Helical
Transmembrane3124-3143Helical
Transmembrane3555-3578Helical
Transmembrane3590-3608Helical
Transmembrane3615-3636Helical
Transmembrane3656-3677Helical
Transmembrane3684-3702Helical
Transmembrane3722-3748Helical
Transmembrane3755-3774Helical

Keywords

PTM/Processing

Features

Showing features for disulfide bond.

TypeIDPosition(s)Description
Disulfide bond2266↔2272

Keywords

Interaction

Subunit

Interacts with host PHB and PHB2.
Interacts with nsp12.
Interacts with nsp7 and nsp8 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13. Interacts with nsp9.
Interacts with nsp7, nsp13 and nsp12 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13.
Interacts with nsp8 and nsp12 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13.
Interacts with nsp8 to form the replication-transcription complex (RTC): nsp12, nsp7, two subunits of nsp8, and up to two subunits of nsp13.
Interacts with papain-like protease nsp3 and non-structural protein 6.
Interacts with proofreading exoribonuclease nsp14 and 2'-O-methyltransferase nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities.
Monomer. Homodimer. Only the homodimer shows catalytic activity.

Family & Domains

Features

Showing features for domain, region, compositional bias.

TypeIDPosition(s)Description
Domain54-196CoV Nsp1 globular
Domain216-246BetaCoV Nsp1 C-terminal
Domain250-514CoV Nsp2 N-terminal
Domain524-713CoV Nsp2 middle
Domain733-851CoV Nsp2 C-terminal
Domain853-966Ubiquitin-like
Region995-1025Disordered
Compositional bias1003-1025Acidic residues
Domain1036-1286Peptidase C16
Domain1264-1435Macro
Domain1491-1563DPUP
Domain1562-1617Ubiquitin-like
Domain1631-1892Peptidase C16
Domain1906-2007Nucleic acid-binding
Domain2020-2169G2M
Domain2235-22963Ecto
Region2383-2473Y1
Domain2383-2750CoV Nsp3 Y
Region2387-2400ZF1
Region2433-2443ZF2
Region2474-2750CoV-Y
Region2650-2750Y4
Domain3149-3246Nsp4C
Domain3247-3549Peptidase C30
Domain3837-3925RdRp Nsp7 cofactor
Domain3926-4122RdRp Nsp8 cofactor
Domain4123-4232Nsp9 ssRNA-binding
Domain4233-4370ExoN/MTase coactivator
Domain4375-4630NiRAN
Domain4631-4729Nsp12 Interface
Domain4730-5297Nsp12 RNA-dependent RNA polymerase
Domain4977-5139RdRp catalytic
Domain5298-5381CV ZBD
Domain5553-5904+RNA virus helicase C-terminal
Domain5971-6186ExoN
Domain6195-6421N7-MTase
Region6308-6322GpppA-binding
Domain6422-6482Nsp15 N-terminal oligomerization
Domain6483-6603AV-Nsp11N/CoV-Nsp15M
Domain6654-6793NendoU
Domain6798-7092Nidovirus-type SAM-dependent 2'-O-MTase

Sequence similarities

Belongs to the coronaviruses polyprotein 1ab family.

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    7,095
  • Mass (Da)
    797,843
  • Last updated
    2017-05-10 v1
  • Checksum
    BE470460957625B9

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1003-1025Acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
KX538964
EMBL· GenBank· DDBJ
AQN78653.1
EMBL· GenBank· DDBJ
Genomic RNA

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