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    ORF1ab ORF1a polyprotein;ORF1ab polyprotein [ Severe acute respiratory syndrome coronavirus 2 ]

    Gene ID: 43740578, updated on 3-Nov-2024

    Summary

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    Gene symbol
    ORF1ab
    Gene description
    ORF1a polyprotein;ORF1ab polyprotein
    Locus tag
    GU280_gp01
    Gene type
    protein coding
    RefSeq status
    PROVISIONAL
    Organism
    Severe acute respiratory syndrome coronavirus 2 (isolate: Wuhan-Hu-1, nat-host: Homo sapiens)
    Lineage
    Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes; Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae; Betacoronavirus; Sarbecovirus
    Summary
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Virus particles include the RNA genetic material and structural proteins needed for invasion of host cells. Once inside the cell the infecting RNA is used to encode structural proteins that make up virus particles, nonstructural proteins that direct virus assembly, transcription, replication and host control and accessory proteins whose function has not been determined.~ ORF1ab, the largest gene, contains overlapping open reading frames that encode polyproteins PP1ab and PP1a. The polyproteins are cleaved to yield 16 nonstructural proteins, NSP1-16. Production of the longer (PP1ab) or shorter protein (PP1a) depends on a -1 ribosomal frameshifting event. The proteins, based on similarity to other coronaviruses, include the papain-like proteinase protein (NSP3), 3C-like proteinase (NSP5), RNA-dependent RNA polymerase (NSP12, RdRp), helicase (NSP13, HEL), endoRNAse (NSP15), 2'-O-Ribose-Methyltransferase (NSP16) and other nonstructural proteins. SARS-CoV-2 nonstructural proteins are responsible for viral transcription, replication, proteolytic processing, suppression of host immune responses and suppression of host gene expression. The RNA-dependent RNA polymerase is a target of antiviral therapies.
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    Genomic context

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    Sequence:
    NC_045512.2 (266..21555)

    NC_045512.2Genomic Context describing neighboring genes Neighboring gene surface glycoprotein Neighboring gene ORF3a protein

    Genomic regions, transcripts, and products

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    Genomic Sequence:
    NC_045512.2

    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Dimerization Tendency of 3CLpros of Human Coronaviruses Based on the X-ray Crystal Structure of the Catalytic Domain of SARS-CoV-2 3CLpro. Jo S, et al. Int J Mol Sci, 2022 May 9. PMID 35563658, Free PMC Article
    2. Development of a High-Throughput Screening Assay to Identify Inhibitors of the SARS-CoV-2 Guanine-N7-Methyltransferase Using RapidFire Mass Spectrometry. Pearson LA, et al. SLAS Discov, 2021 Jul. PMID 33724070, Free PMC Article
    3. From Repurposing to Redesign: Optimization of Boceprevir to Highly Potent Inhibitors of the SARS-CoV-2 Main Protease. Göhl M, et al. Molecules, 2022 Jul 4. PMID 35807537, Free PMC Article
    4. Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease. Frazier MN, et al. Nucleic Acids Res, 2022 Aug 12. PMID 35801916, Free PMC Article
    5. Direct Observation of Protonation State Modulation in SARS-CoV-2 Main Protease upon Inhibitor Binding with Neutron Crystallography. Kneller DW, et al. J Med Chem, 2021 Apr 22. PMID 33755450, Free PMC Article

    See all (381) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Characterization of the Conformational Hotspots of the RNA-Dependent RNA Polymerase Complex Identifies a Unique Structural Malleability of nsp8.
      Title: Characterization of the Conformational Hotspots of the RNA-Dependent RNA Polymerase Complex Identifies a Unique Structural Malleability of nsp8.
    2. Structural and functional insights into the 2'-O-methyltransferase of SARS-CoV-2.
      Title: Structural and functional insights into the 2'-O-methyltransferase of SARS-CoV-2.
    3. Deletion of 82-85 N-Terminal Residues in SARS-CoV-2 Nsp1 Restricts Virus Replication.
      Title: Deletion of 82-85 N-Terminal Residues in SARS-CoV-2 Nsp1 Restricts Virus Replication.
    4. Binding of SARS-CoV-2 Nonstructural Protein 1 to 40S Ribosome Inhibits mRNA Translation.
      Title: Binding of SARS-CoV-2 Nonstructural Protein 1 to 40S Ribosome Inhibits mRNA Translation.
    5. Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication.
      Title: Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication.
    6. In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.
      Title: In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.
    7. Structural, energetic and lipophilic analysis of SARS-CoV-2 non-structural protein 9 (NSP9).
      Title: Structural, energetic and lipophilic analysis of SARS-CoV-2 non-structural protein 9 (NSP9).
    8. Backbone chemical shift spectral assignments of SARS coronavirus-2 non-structural protein nsp9.
      Title: Backbone chemical shift spectral assignments of SARS coronavirus-2 non-structural protein nsp9.
    9. Characterization of nsp1 Binding to the Viral RNA Leader Sequence of Severe Acute Respiratory Syndrome Coronavirus.
      Title: Characterization of nsp1 Binding to the Viral RNA Leader Sequence of Severe Acute Respiratory Syndrome Coronavirus.
    10. Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.
      Title: Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.
    Submit: New GeneRIF Correction See all GeneRIFs (160)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    stem_loop

    • Loc: 13476-13503 function = Coronavirus frameshifting stimulation element stem-loop 1 , inference = COORDINATES: profile:Rfam-release-14.1:RF00507,Infernal:1.1.2
    • Loc: 13488-13542 function = Coronavirus frameshifting stimulation element stem-loop 2 , inference = COORDINATES: profile:Rfam-release-14.1:RF00507,Infernal:1.1.2

    General protein information

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    Preferred Names
    ORF1a polyprotein;ORF1ab polyprotein
    Names
    leader protein
    nsp2
    nsp3
    nsp4
    3C-like proteinase
    nsp6
    nsp7
    nsp8
    nsp9
    nsp10
    RNA-dependent RNA polymerase
    helicase
    3'-to-5' exonuclease
    endoRNAse
    2'-O-ribose methyltransferase
    leader protein
    nsp2
    nsp3
    nsp4
    3C-like proteinase
    nsp6
    nsp7
    nsp8
    nsp9
    nsp10
    nsp11
    YP_009724389.1
    • pp1ab; translated by -1 ribosomal frameshift
    YP_009725295.1
    • pp1a

    NCBI Reference Sequences (RefSeq)

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    Genome Annotation

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference assembly

    Genomic

    1. NC_045512.2 Reference assembly

      Range
      266..21555
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. YP_009724389.1 ORF1ab polyprotein [Severe acute respiratory syndrome coronavirus 2]

      Status: PROVISIONAL

      UniProtKB/Swiss-Prot
      P0DTD1
      UniProtKB/TrEMBL
      A0A679G4D8, A0A6B9UY63, A0A6B9V049, A0A6B9VSU5, A0A6B9WIH5, A0A6C0M7K8, A0A6C0RS15, A0A6C0T6V0, A0A6C1F1G5, A0A6G7CR93, A0A6H2L6K3, A0A6H2TXR8, A0A6M3DDN3, A0A6M3GZB3, A0A6M3HQ10, A0A6M3HT58, A0A6M3T1R2, A0A6M5WPR7, A0A6M8EHB3, A0A6N1W2H4, A0A6V7AKV6, A0A6V7ALW7, A0A7I0YLY4, A0A7U3MRI0, A0A7U3MX55, A0A7U3RLH4, A0A883GPD4, A0A886NG00
      Conserved Domains (29) summary
      pfam11633
      Location:1351 → 1493
      SUD-M; Single-stranded poly(A) binding domain
      cd21401
      Location:5325 → 5419
      ZBD_cv_Nsp13-like; Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins
      cd21409
      Location:5474 → 5552
      1B_cv_Nsp13-like; 1B domain of coronavirus SARS NSP13 helicase and related proteins
      cd21473
      Location:2777 → 3157
      cv_Nsp4_TM; coronavirus non-structural protein 4 (Nsp4) transmembrane domain
      cd21525
      Location:1496 → 1561
      SUD_C_SARS-CoV_Nsp3; C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage
      cd21560
      Location:3570 → 3859
      betaCoV-Nsp6; betacoronavirus non-structural protein 6
      cd21516
      Location:182 → 818
      cv_beta_Nsp2_SARS-like; betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage
      cd21557
      Location:1054 → 1177
      Macro_X_Nsp3-like; X-domain of viral non-structural protein 3 and related macrodomains
      cd21666
      Location:3267 → 3563
      betaCoV_Nsp5_Mpro; betacoronavirus non-structural protein 5, also called Main protease (Mpro)
      cd21591
      Location:4397 → 5324
      SARS-CoV-like_RdRp; Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome
      cd21171
      Location:6453 → 6513
      NTD_alpha_beta_cv_Nsp15-like; N-terminal domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins
      cd21167
      Location:6517 → 6648
      M_alpha_beta_cv_Nsp15-like; middle domain of alpha- and beta-coronavirus Nonstructural protein 15 (Nsp15), and related proteins
      cd21161
      Location:6646 → 6796
      NendoU_cv_Nsp15-like; Nidoviral uridylate-specific endoribonuclease (NendoU) domain of coronavirus Nonstructural Protein 15 (Nsp15) and related proteins
      cd21659
      Location:5930 → 6450
      betaCoV_Nsp14; nonstructural protein 14 of betacoronavirus
      pfam06460
      Location:6800 → 7095
      NSP13; Coronavirus NSP13
      pfam08717
      Location:3943 → 4139
      nsp8; nsp8 replicase
      pfam12379
      Location:880 → 1050
      DUF3655; Protein of unknown function (DUF3655)
      pfam16348
      Location:3169 → 3261
      Corona_NSP4_C; Coronavirus nonstructural protein 4 C-terminus
      cd21827
      Location:3860 → 3942
      betaCoV_Nsp7; betacoronavirus non-structural protein 7
      cd21901
      Location:4254 → 4384
      alpha_betaCoV_Nsp10; alphacoronavirus and betacoronavirus non-structural protein 14
      cd21898
      Location:4141 → 4253
      betaCoV_Nsp9; betacoronavirus non-structural protein 9
      cd21796
      Location:13 → 127
      SARS-CoV-like_Nsp1_N; N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21822
      Location:1913 → 2019
      SARS-CoV-like_Nsp3_NAB; nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21814
      Location:2044 → 2159
      SARS-CoV-like_Nsp3_betaSM; betacoronavirus-specific marker of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21732
      Location:1566 → 1868
      betaCoV_PLPro; betacoronavirus papain-like protease
      cd21722
      Location:5575 → 5914
      betaCoV_Nsp13-helicase; helicase domain of betacoronavirus non-structural protein 13
      cd21717
      Location:2232 → 2762
      TM_Y_SARS-CoV-like_Nsp3_C; C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21689
      Location:5423 → 5470
      stalk_CoV_Nsp13-like; stalk domain of coronavirus Nsp13 helicase and related proteins
      cl00019
      Location:1233 → 1358
      Macro_SF; macrodomain superfamily

    2. YP_009725297.1 leader protein

      UniProtKB/TrEMBL
      A0A6M8NMS9, A0A6M8NRD9
      Conserved Domains (1) summary
      cl41742
      Location:13 → 127
      alpha_betaCoV_Nsp1; non-structural protein 1 from alpha- and betacoronavirus

    3. YP_009725298.1 nsp2

      Conserved Domains (1) summary
      cd21516
      Location:2 → 638
      cv_beta_Nsp2_SARS-like; betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage

    4. YP_009725299.1 nsp3

      Conserved Domains (8) summary
      pfam12124
      Location:680 → 743
      Nsp3_PL2pro; Coronavirus polyprotein cleavage domain
      pfam12379
      Location:102 → 169
      DUF3655; Protein of unknown function (DUF3655)
      pfam16251
      Location:1089 → 1201
      NAR; Nucleic acid-binding domain (NAR)
      pfam11633
      Location:533 → 675
      SUD-M; Single-stranded poly(A) binding domain
      cd14964
      Location:1497 → 1519
      7tm_GPCRs; TM helix 5 [structural motif]
      pfam01661
      Location:240 → 340
      Macro; Macro domain
      pfam08715
      Location:746 → 1064
      Viral_protease; Papain like viral protease
      cl28897
      Location:1494 → 1563
      7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

    5. YP_009725300.1 nsp4

      Conserved Domains (1) summary
      pfam16348
      Location:406 → 498
      Corona_NSP4_C; Coronavirus nonstructural protein 4 C-terminus

    6. YP_009725301.1 3C-like proteinase

      Conserved Domains (1) summary
      cd21666
      Location:4 → 300
      betaCoV_Nsp5_Mpro; betacoronavirus non-structural protein 5, also called Main protease (Mpro)

    7. YP_009725302.1 nsp6

    8. YP_009725303.1 nsp7

      Conserved Domains (1) summary
      cd21827
      Location:1 → 83
      betaCoV_Nsp7; betacoronavirus non-structural protein 7

    9. YP_009725304.1 nsp8

      Conserved Domains (1) summary
      pfam08717
      Location:1 → 197
      nsp8; nsp8 replicase

    10. YP_009725305.1 nsp9

      Conserved Domains (1) summary
      cd21898
      Location:1 → 113
      betaCoV_Nsp9; betacoronavirus non-structural protein 9

    11. YP_009725306.1 nsp10

      UniProtKB/TrEMBL
      G8H303
      Conserved Domains (1) summary
      cl40460
      Location:1 → 131
      CoV_Nsp10; coronavirus non-structural protein 10

    12. YP_009725307.1 RNA-dependent RNA polymerase

      Conserved Domains (1) summary
      cd21591
      Location:5 → 932
      SARS-CoV-like_RdRp; Severe acute respiratory syndrome coronavirus RNA-dependent RNA polymerase, also known as non-structural protein 12, and similar proteins from betacoronaviruses in the B lineage: responsible for replication and transcription of the viral RNA genome

    13. YP_009725308.1 helicase

      Conserved Domains (4) summary
      cd21401
      Location:1 → 95
      ZBD_cv_Nsp13-like; Cys/His rich zinc-binding domain (CH/ZBD) of coronavirus SARS NSP13 helicase and related proteins
      cd21409
      Location:150 → 228
      1B_cv_Nsp13-like; 1B domain of coronavirus SARS NSP13 helicase and related proteins
      cd21722
      Location:251 → 590
      betaCoV_Nsp13-helicase; helicase domain of betacoronavirus non-structural protein 13
      cd21689
      Location:99 → 146
      stalk_CoV_Nsp13-like; stalk domain of coronavirus Nsp13 helicase and related proteins

    14. YP_009725309.1 3'-to-5' exonuclease

      Conserved Domains (1) summary
      cl40464
      Location:5 → 525
      CoV_Nsp14; nonstructural protein 14 of coronavirus

    15. YP_009725310.1 endoRNAse

      Conserved Domains (1) summary
      pfam06471
      Location:1 → 68
      NSP11

    16. YP_009725311.1 2'-O-ribose methyltransferase

      Conserved Domains (1) summary
      pfam06460
      Location:2 → 297
      NSP13; Coronavirus NSP13

    17. YP_009725295.1 ORF1a polyprotein [Severe acute respiratory syndrome coronavirus 2]

      Status: PROVISIONAL

      UniProtKB/Swiss-Prot
      P0DTC1
      UniProtKB/TrEMBL
      A0A6C0RSH1, A0A6G6A224, A0A6G7KRG6, A0A6H0C7F2, A0A6H0JG04, A0A6M3HSG4, A0A6M3VXV6, A0A6M3WSK0, A0A6M5WJ06, A0A6M5WNZ9, A0A6M6JVJ9, A0A7D5JHC2, A0A7G6WCV0, A0A7G9UIU5, A0A7H4JDL9, A0A7T4X8V7, A0A7U1D8T7, A0A7U3HE26, A0A7U3QAS2, A0A883GPP4, A0A883GQI3, A0A883GR30, A0A897FAK2, A0A897FEG2, A0A8B1JJQ7, A0A8B1JX69, A0A8B6RCQ2
      Conserved Domains (19) summary
      pfam11633
      Location:1351 → 1493
      SUD-M; Single-stranded poly(A) binding domain
      cd21473
      Location:2777 → 3157
      cv_Nsp4_TM; coronavirus non-structural protein 4 (Nsp4) transmembrane domain
      cd21525
      Location:1496 → 1561
      SUD_C_SARS-CoV_Nsp3; C-terminal SARS-Unique Domain (SUD) of non-structural protein 3 (Nsp3) from Severe Acute Respiratory Syndrome coronavirus and related betacoronaviruses in the B lineage
      cd21560
      Location:3570 → 3859
      betaCoV-Nsp6; betacoronavirus non-structural protein 6
      cd21516
      Location:182 → 818
      cv_beta_Nsp2_SARS-like; betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage
      cd21557
      Location:1054 → 1177
      Macro_X_Nsp3-like; X-domain of viral non-structural protein 3 and related macrodomains
      cd21666
      Location:3267 → 3563
      betaCoV_Nsp5_Mpro; betacoronavirus non-structural protein 5, also called Main protease (Mpro)
      pfam08717
      Location:3943 → 4139
      nsp8; nsp8 replicase
      pfam12379
      Location:880 → 1050
      DUF3655; Protein of unknown function (DUF3655)
      pfam16348
      Location:3169 → 3261
      Corona_NSP4_C; Coronavirus nonstructural protein 4 C-terminus
      cd21827
      Location:3860 → 3942
      betaCoV_Nsp7; betacoronavirus non-structural protein 7
      cd21901
      Location:4254 → 4384
      alpha_betaCoV_Nsp10; alphacoronavirus and betacoronavirus non-structural protein 14
      cd21898
      Location:4141 → 4253
      betaCoV_Nsp9; betacoronavirus non-structural protein 9
      cd21796
      Location:13 → 127
      SARS-CoV-like_Nsp1_N; N-terminal domain of non-structural protein 1 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21822
      Location:1913 → 2019
      SARS-CoV-like_Nsp3_NAB; nucleic acid binding domain of non-structural protein 3 from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cd21732
      Location:1566 → 1868
      betaCoV_PLPro; betacoronavirus papain-like protease
      cd21717
      Location:2232 → 2762
      TM_Y_SARS-CoV-like_Nsp3_C; C-terminus of non-structural protein 3, including transmembrane and Y domains, from Severe acute respiratory syndrome-related coronavirus and betacoronavirus in the B lineage
      cl00019
      Location:1233 → 1358
      Macro_SF; macrodomain superfamily
      cl41743
      Location:2044 → 2159
      betaCoV_Nsp3_betaSM; betacoronavirus-specific marker of betacoronavirus non-structural protein 3

    18. YP_009742608.1 leader protein

      UniProtKB/TrEMBL
      A0A6M8NMS9, A0A6M8NRD9
      Conserved Domains (1) summary
      cl41742
      Location:13 → 127
      alpha_betaCoV_Nsp1; non-structural protein 1 from alpha- and betacoronavirus

    19. YP_009742609.1 nsp2

      Conserved Domains (1) summary
      cd21516
      Location:2 → 638
      cv_beta_Nsp2_SARS-like; betacoronavirus non-structural protein 2 (Nsp2) similar to SARS-CoV Nsp2, and related proteins from betacoronaviruses in the B lineage

    20. YP_009742610.1 nsp3

      Conserved Domains (8) summary
      pfam12124
      Location:680 → 743
      Nsp3_PL2pro; Coronavirus polyprotein cleavage domain
      pfam12379
      Location:102 → 169
      DUF3655; Protein of unknown function (DUF3655)
      pfam16251
      Location:1089 → 1201
      NAR; Nucleic acid-binding domain (NAR)
      pfam11633
      Location:533 → 675
      SUD-M; Single-stranded poly(A) binding domain
      cd14964
      Location:1497 → 1519
      7tm_GPCRs; TM helix 5 [structural motif]
      pfam01661
      Location:240 → 340
      Macro; Macro domain
      pfam08715
      Location:746 → 1064
      Viral_protease; Papain like viral protease
      cl28897
      Location:1494 → 1563
      7tm_GPCRs; seven-transmembrane G protein-coupled receptor superfamily

    21. YP_009742611.1 nsp4

      Conserved Domains (1) summary
      pfam16348
      Location:406 → 498
      Corona_NSP4_C; Coronavirus nonstructural protein 4 C-terminus

    22. YP_009742612.1 3C-like proteinase

      Conserved Domains (1) summary
      cd21666
      Location:4 → 300
      betaCoV_Nsp5_Mpro; betacoronavirus non-structural protein 5, also called Main protease (Mpro)

    23. YP_009742613.1 nsp6

    24. YP_009742614.1 nsp7

      Conserved Domains (1) summary
      cd21827
      Location:1 → 83
      betaCoV_Nsp7; betacoronavirus non-structural protein 7

    25. YP_009742615.1 nsp8

      Conserved Domains (1) summary
      pfam08717
      Location:1 → 197
      nsp8; nsp8 replicase

    26. YP_009742616.1 nsp9

      Conserved Domains (1) summary
      cd21898
      Location:1 → 113
      betaCoV_Nsp9; betacoronavirus non-structural protein 9

    27. YP_009742617.1 nsp10

      UniProtKB/TrEMBL
      G8H303
      Conserved Domains (1) summary
      cl40460
      Location:1 → 131
      CoV_Nsp10; coronavirus non-structural protein 10

    28. YP_009725312.1 nsp11

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P0DTC1.1 P0DTC1
    P0DTD1.1 P0DTD1

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