P0C6V5 · R1A_IBVM

Function

function

Isoform Replicase polyprotein 1a

Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.

Non-structural protein 2

May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (By similarity).
Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (By similarity).

Papain-like protease

Responsible for the cleavages located at the N-terminus of the replicase polyprotein (By similarity).
In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (By similarity).

Non-structural protein 4

Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (By similarity).
Alone is able to induce paired membranes (By similarity).
Coexpression of nsp3 and nsp4 does not result in the formation of DMVs (By similarity).

3C-like proteinase

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.

Non-structural protein 7

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.

Non-structural protein 8

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.

Non-structural protein 9

Plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA.

Non-structural protein 10

Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities (By similarity).
Therefore plays an essential role in viral mRNAs cap methylation (By similarity).

Catalytic activity

  • Papain-like protease

    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).
    EC:3.4.19.12 (UniProtKB | ENZYME | Rhea)

Cofactor

Papain-like protease

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Features

Showing features for site, active site, binding site.

TypeIDPosition(s)Description
Site673-674Cleavage; by PL-PRO
Active site1276For PL-PRO activity
Active site1439For PL-PRO activity
Active site1450For PL-PRO activity
Binding site1917Zn2+ 1 (UniProtKB | ChEBI)
Binding site1922Zn2+ 1 (UniProtKB | ChEBI)
Binding site1927Zn2+ 1 (UniProtKB | ChEBI)
Binding site1930Zn2+ 1 (UniProtKB | ChEBI)
Binding site1963Zn2+ 2 (UniProtKB | ChEBI)
Binding site1966Zn2+ 2 (UniProtKB | ChEBI)
Binding site1970Zn2+ 2 (UniProtKB | ChEBI)
Binding site1973Zn2+ 2 (UniProtKB | ChEBI)
Site2267-2268Cleavage; by PL-PRO
Site2781-2782Cleavage; by 3CL-PRO
Active site2822For 3CL-PRO activity
Active site2924For 3CL-PRO activity
Site3088-3089Cleavage; by 3CL-PRO
Site3381-3382Cleavage; by 3CL-PRO
Site3464-3465Cleavage; by 3CL-PRO
Site3674-3675Cleavage; by 3CL-PRO
Site3785-3786Cleavage; by 3CL-PRO
Binding site3860Zn2+ 3 (UniProtKB | ChEBI)
Binding site3863Zn2+ 3 (UniProtKB | ChEBI)
Binding site3869Zn2+ 3 (UniProtKB | ChEBI)
Binding site3880Zn2+ 3 (UniProtKB | ChEBI)
Binding site3906Zn2+ 4 (UniProtKB | ChEBI)
Binding site3909Zn2+ 4 (UniProtKB | ChEBI)
Binding site3917Zn2+ 4 (UniProtKB | ChEBI)
Binding site3919Zn2+ 4 (UniProtKB | ChEBI)
Site3930-3931Cleavage; by 3CL-PRO

GO annotations

AspectTerm
Cellular Componenthost cell endoplasmic reticulum membrane
Cellular Componenthost cell perinuclear region of cytoplasm
Cellular Componentmembrane
Molecular Functioncysteine-type endopeptidase activity
Molecular Functionlyase activity
Molecular Functionomega peptidase activity
Molecular FunctionRNA binding
Molecular Functiontransferase activity
Molecular Functionzinc ion binding
Biological Processinduction by virus of host autophagy
Biological Processproteolysis
Biological Processviral genome replication
Biological Processviral protein processing
Biological Processviral translational frameshifting

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

Gene names

    • ORF names
      1a

Organism names

Accessions

  • Primary accession
    P0C6V5
  • Secondary accessions
    • Q0GNB9

Proteomes

Subcellular Location

Papain-like protease

Host endoplasmic reticulum membrane
; Multi-pass membrane protein
Host cytoplasm
Note: Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER).

Non-structural protein 4

Host endoplasmic reticulum membrane
; Multi-pass membrane protein
Host cytoplasm
Note: Localizes in virally-induced cytoplasmic double-membrane vesicles (By similarity).
Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER) (By similarity).

Non-structural protein 6

Host endoplasmic reticulum membrane
; Multi-pass membrane protein
Note: Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER).

Non-structural protein 7

Host cytoplasm
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.

Non-structural protein 8

Host cytoplasm
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.

Non-structural protein 9

Host cytoplasm
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.

Non-structural protein 10

Host cytoplasm
Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-1752Cytoplasmic
Transmembrane1753-1773Helical
Topological domain1774-1845Lumenal
Transmembrane1846-1866Helical
Topological domain1867-2282Cytoplasmic
Transmembrane2283-2303Helical
Topological domain2304-2561Lumenal
Transmembrane2562-2582Helical
Topological domain2583-2613Cytoplasmic
Transmembrane2614-2634Helical
Topological domain2635-2645Lumenal
Transmembrane2646-2666Helical
Topological domain2667-3098Cytoplasmic
Transmembrane3099-3119Helical
Topological domain3120-3123Lumenal
Transmembrane3124-3144Helical
Topological domain3145-3153Cytoplasmic
Transmembrane3154-3174Helical
Topological domain3175-3190Lumenal
Transmembrane3191-3211Helical
Topological domain3212-3259Cytoplasmic
Transmembrane3260-3280Helical
Topological domain3281-3298Lumenal
Transmembrane3299-3319Helical
Topological domain3320-3953Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant807
Natural variant1618
Natural variant1739
Natural variant2631
Natural variant2774

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 5 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00003383371-673Non-structural protein 2
ChainPRO_00003383361-3953Replicase polyprotein 1a
ChainPRO_0000338338674-2267Papain-like protease
Disulfide bond1787↔1813
Disulfide bond1804↔1810
ChainPRO_00003383392268-2781Non-structural protein 4
ChainPRO_00003383402782-30883C-like proteinase
ChainPRO_00003383413089-3381Non-structural protein 6
ChainPRO_00003383423382-3464Non-structural protein 7
ChainPRO_00003383433465-3674Non-structural protein 8
ChainPRO_00003383443675-3785Non-structural protein 9
ChainPRO_00003383453786-3930Non-structural protein 10
ChainPRO_00003383463931-3953Non-structural protein 11

Post-translational modification

Isoform Replicase polyprotein 1a

Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (By similarity).
3C-like proteinase nsp5 liberates nsps 6-16 from the polyprotein (By similarity).
Papain-like and 3C-like proteinases are autocatalytically processed

Non-structural protein 4

N-glycosylated.

Keywords

Interaction

Subunit

Non-structural protein 2

Interacts with host PHB and PHB2.

Non-structural protein 4

Interacts with papain-like protease and non-structural protein 6.

3C-like proteinase

Monomer (PubMed:18987156).
Homodimer (PubMed:18987156).
Only the homodimer shows catalytic activity (By similarity).

Non-structural protein 7

Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure.

Non-structural protein 8

Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure (By similarity).
Interacts with ORF6 protein (By similarity).

Non-structural protein 9

Homodimer.

Non-structural protein 10

Homododecamer.

Structure

Family & Domains

Features

Showing features for domain, zinc finger, region.

TypeIDPosition(s)Description
Domain675-780Ubiquitin-like 1
Domain1005-1181Macro
Domain1177-1229Ubiquitin-like 2
Domain1238-1499Peptidase C16
Zinc finger1355-1392C4-type; degenerate
Region1753-1866HD1
Domain1771-18353Ecto
Region1913-2003Y1
Domain1913-2265CoV Nsp3 Y
Region1917-1930ZF1
Region1963-1973ZF2
Region2004-2106Y2
Region2004-2265CoV-Y
Region2107-2165Y3
Region2166-2265Y4
Region2283-2666HD2
Domain2686-2781Nsp4C
Domain2782-3088Peptidase C30
Region3099-3319HD3
Domain3382-3464RdRp Nsp7 cofactor
Domain3465-3674RdRp Nsp8 cofactor
Domain3675-3785Nsp9 ssRNA-binding
Domain3787-3928ExoN/MTase coactivator
Zinc finger3860-3880
Zinc finger3906-3919

Domain

Papain-like protease

The hydrophobic region HD1 probably mediates the membrane association of the replication complex.

Non-structural protein 4

The hydrophobic region HD2 probably mediates the membrane association of the replication complex.

Non-structural protein 6

The hydrophobic region HD3 probably mediates the membrane association of the replication complex.

Sequence similarities

Keywords

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Ribosomal frameshifting. Isoform Replicase polyprotein 1ab is produced by -1 ribosomal frameshifting at the 1a-1b genes boundary. Isoform Replicase polyprotein 1a is produced by conventional translation.

P0C6V5-1

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.

  • Name
    Replicase polyprotein 1a
  • Synonyms
    pp1a, ORF1a polyprotein
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    3,953
  • Mass (Da)
    441,177
  • Last updated
    2008-06-10 v1
  • Checksum
    70AB99DED32F2B89
MASSLKQGVSPKLRDVILVSKDIPEQLCDALFFYTSHNPKDYADAFAVRQKFDRNLQTGKQFKFETVCGLFLLKGVDKITPGVPAKVLKATSKLADLEDIFGVSPFARKYRELLKTACQWSLTVETLDARAQTLDEIFDPTEILWLQVAAKIQVSAMAMRRLVGEVTAKVMDALGSNMSALFQIFKQQIVRIFQKALAIFENVSELPQRIAALKMAFAKCAKSITVVVMERTLVVREFAGTCLASINGAVAKFFEELPNGFMGAKIFTTLAFFREAAVKIVDNIPNAPRGTKGFEVVGNAKGTQVVVRGMRNDLTLLDQKAEIPVESEGWSAILGGHLCYVFKSGDRFYAAPLSGNFALHDVHCCERVVCLSDGVTPEINDGLILAAIYSSFSVAELVAAIKRGEPFKFLGHKFVYAKDAAVSFTLAKAATIADVLKLFQSARVKVEDVWSSLTEKSFEFWRLAYGKVRNLEEFVKTCFCKAQMAIVILATVLGEGIWHLVSQVIYKVGGLFTKVVDFCEKYWKGFCAQLKRAKLIVTETLCVLKGVAQHCFQLLLDAIQFMYKSFKKCALGRIHGDLLFWKGGVHKIIQEGDEIWFDAIDSIDVEDLGVVQEKLIDFDVCDNVTLPENQPGHMVQIEDDGKNYMFFRFKKDENIYYTPMSQLGAINVVCKAGGKTVTFGETTVQEIPPPDVVFIKVSIECCGEPWNTIFKKAYKEPIEVETDLTVEQLLSVVYEKMCDDLKLFPEAPEPPPFENVTLVDKNGKDLDCIKSCHLIYRDYESDDDIEEEDAEECDTDSGDAEECDTNLECEEEDEDTKVLALIQDPASNKYPLPLDDDYSVYNGCIVHKDALDVVNLPSGEETFVVNNCFEGAVKALPQKVIDVLGDWGEAVDAQEQLCQQESTRVISEKSVEGFTGSCDAMAEQAIVEEQEIVPVVEQSQDVVVFTPADLEVVKETAEEVDEFILISAVPKEEVVSQEKEEPQVEQEPTLVVKAQREKKAKKFKVKPATCEKPKFLEYKTCVGDLAVVIAKALDEFKEFCIVNAANEHMSHGGGVAKAIADFCGPDFVEYCADYVKKHGPQQKLVTPSFVKGIQCVNNVVGPRHGDSNLREKLVAAYKSVLVGGVVNYVVPVLSSGIFGVDFKISIDAMREAFKGCAIRVLLFSLSQEHIDYFDATCKQKTIYLTEDGVKYRSVVLKPGDSLGQFGQVFARNKVVFSADDVEDKEILFIPTTDKTILEYYGLDAQKYVTYLQTLAQKWDVQYRDNFVILEWRDGNCWISSAIVLLQAAKIRFKGFLAEAWAKLLGGDPTDFVAWCYASCNAKVGDFSDANWLLANLAEHFDADYTNALLKKCVSCNCGVKSYELRGLEACIQPVRAPNLLHFKTQYSNCPTCGASSTDEVIEASLPYLLLFATDGPATVDCDENAVGTVVFIGSTNSGHCYTQADGKAFDNLAKDRKFGRKSPYITAMYTRFSLRSENPLLVVEHSKGKAKVVKEDVSNLATSSKASFDDLTDFEQWYDSNIYESLKVQETPDNLDEYVSFTTKEDSKLPLTLKVRGIKSVVDFRSKDGFTYKLTPDTDENSKTPVYYPVLDSISLRAIWVEGSANFVVGHPNYYSKSLRIPTFWENAESFVKMGYKIDGVTMGLWRAEHLNKPNLERIFNIAKKAIVGSSVVTTQCGKILVKAATYVADKVGDGVVRNITDRIKGLCGFTRGHFEKKMSLQFLKTLVFFFFYFLKASSKSLVSSYKIVLCKVVFATLLIVWFIYTSNPVVFTGIRVLDFLFEGSLCGPYNDYGKDSFDVLRYCAGDFTCRVCLHDRDSLHLYKHAYSVEQIYKDAASGINFNWNWLYLVFLILFVKPVAGFVIICYCVKYLVLSSTVLQTGVGFLDWFVKTVFTHFNFMGAGFYFWLFYKIYVQVHHILYCKDVTCEVCKRVARSNRQEVSVVVGGRKQIVHVYTNSGYNFCKRHNWYCRNCDDYGHQNTFMSPEVAGELSEKLKRHVKPTAYAYHVVYEACVVDDFVNLKYKAAIPGKDNASSAVKCFSVTDFLKKAVFLKEALKCEQISNDGFIVCNTQSAHALEEAKNAAVYYAQYLCKPILILDQALYEQLIVEPVSKSVIDKVCSILSNIISVDTAALNYKAGTLRDALLSITKDEEAVDMAIFCHNHEVEYTGDGFTNVIPSYGMDTDKLTPRDRGFLINADASIANLRVKNAPPVVWKFSDLIKLSDSCLKYLISATVKSGGRFFITKSGAKQVISCHTQKLLVEKKAGGVINNTFKWFMSCFKWLFVFYILFTACCLGYYYMEMNKSFVHPMYDVNSTLHVEGFKVIDKGVIREIVSEDNCFSNKFVNFDAFWGKSYENNKNCPIVTVVIDGDGTVAVGVPGFVSWVMDGVMFVHMTQTDRRPWYIPTWFNREIVGYTQDSIITEGSFYTSIALFSARCLYLTASNTPQLYCFNGDNDAPGALPFGSIIPHRVYFQPNGVRLIVPQQILHTPYIVKFVSDSYCRGSVCEYTKPGYCVSLDSQWVLFNDEYISKPGVFCGSTVRELMFNMVSTFFTGVNPNIYIQLATMFLILVVIVLIFAMVIKFQGVFKAYATIVFTIMLVWVINAFVLCVHSYNSVLAVILLVLYCYASMVTSRNTAIIMHCWLVFTFGLIVPTWLACCYLGFILYMYTPLVFWCYGTTKNTRKLYDGNEFVGNYDLAAKSTFVIRGTEFVKLTNEIGDKFEAYLSAYARLKYYSGTGSEQDYLQACRAWLAYALDQYRNSGVEVVYTPPRYSIGVSRLQAGFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLGKFSGDQWGDVLNLANNHEFEVVTQNGVTLNVVSRRLKGAVLILQTAVANAETPKYKFVKANCGDSFTIACSYGGTVIGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFYMHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKESSFSQPKWLESTTVSIEDYNRWASDNGFTPFSTSTAITKLSAITGVDVCKLLRTIMVKSAQWGSDPILGQYNFEDELTPESVFNQVGGVRLQSSFVRKATSWFWSRCVLACFLFVLCAIVLFTAVPLKFYVHAAVILLMAVLFISFTVKHVMAYMDTFLLPTLITVIIGVCAEVPFIYNTLISQVVIFLSQWYDPVVFDTMVPWMLLPLVLYTAFKCVQGCYMNSFNTSLLMLYQFMKLGFVIYTSSNTLTAYTEGNWELFFELVHTIVLANVSSNSLIGLIVFKCAKWMLYYCNATYFNNYVLMAVMVNGIGWLCTCYFGLYWWVNKVFGLTLGKYNFKVSVDQYRYMCLHKVNPPKTVWEVFTTNILIQGIGGDRVLPIATVQSKLSDVKCTTVVLMQLLTKLNVEANSKMHAYLVELHNKILASDDVGECMDNLLGMLITLFCIDSTIDLGEYCDDILKRSTVLQSVTQEFSHIPSYAEYERAKSIYEKVLADSKNGGVTQQELAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARVTDRRAKLVSSLHALLFSMLKKIDSEKLNVLFDQANSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGVHVTYSTVVWNIDCVTDADGTELHPTSTGSGLTYCISGDNIAWPLKVNLTRNGHNKVDVALQNNELMPHGVKTKACVAGVDQAHCSVESKCYYTSISGSSVVAAITSSNPNLKVASFLNEAGNQIYVDLDPPCKFGMKVGDKVEVVYLYFIKNTRSIVRGMVLGAISNVVVLQSKGHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHNGSGFAITSKPSPTPDQDSYGGASVCLYCRAHIAHPGGAGNLDGRCQFKGSFVQIPTTEKDPVGFCLRNKVCTVCQCWIGYGCQCDSLRQPKPSVQSVAVASGFDKNYLNGYGVAVRLG

P0C6Y3-1

The sequence of this isoform can be found in the external entry linked below. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

View isoform
  • Name
    Replicase polyprotein 1ab
  • Synonyms
    pp1ab
  • See also
    sequence in UniParc or sequence clusters in UniRef

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ834384
EMBL· GenBank· DDBJ
ABI26421.1
EMBL· GenBank· DDBJ
Genomic RNA
AY851295
EMBL· GenBank· DDBJ
AAW33784.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

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