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P0C6Y0

- R1AB_CVMJH

UniProt

P0C6Y0 - R1AB_CVMJH

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Protein
Replicase polyprotein 1ab
Gene
rep, 1a-1b
Organism
Murine coronavirus (strain JHM) (MHV-JHM) (Murine hepatitis virus)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 (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.
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.
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.

Catalytic activityi

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
ATP + H2O = ADP + phosphate.
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).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei247 – 2482Cleavage; by PL1-PRO Inferred
Sitei832 – 8332Cleavage; by PL1-PRO Inferred
Active sitei1120 – 11201For PL1-PRO activity By similarity
Active sitei1271 – 12711For PL1-PRO activity By similarity
Active sitei1715 – 17151For PL2-PRO activity By similarity
Active sitei1872 – 18721For PL2-PRO activity By similarity
Sitei2840 – 28412Cleavage; by PL2-PRO Inferred
Sitei3336 – 33372Cleavage; by 3CL-PRO Inferred
Active sitei3377 – 33771For 3CL-PRO activity By similarity
Active sitei3481 – 34811For 3CL-PRO activity By similarity
Sitei3639 – 36402Cleavage; by 3CL-PRO Inferred
Sitei3927 – 39282Cleavage; by 3CL-PRO Inferred
Sitei4019 – 40202Cleavage; by 3CL-PRO Inferred
Sitei4213 – 42142Cleavage; by 3CL-PRO Inferred
Sitei4323 – 43242Cleavage; by 3CL-PRO Inferred
Sitei4460 – 44612Cleavage; by 3CL-PRO Inferred
Sitei5388 – 53892Cleavage; by 3CL-PRO Inferred
Sitei5988 – 59892Cleavage; by 3CL-PRO Inferred
Sitei6507 – 65082Cleavage; by 3CL-PRO Inferred
Sitei6881 – 68822Cleavage; by 3CL-PRO Inferred

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri1197 – 122529C4-type 1
Add
BLAST
Zinc fingeri1793 – 182937C4-type 2
Add
BLAST
Zinc fingeri4397 – 441317 By similarity
Add
BLAST
Zinc fingeri4439 – 445214 By similarity
Add
BLAST
Nucleotide bindingi5669 – 56768ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. RNA binding Source: UniProtKB-KW
  3. RNA-directed RNA polymerase activity Source: UniProtKB-KW
  4. cysteine-type endopeptidase activity Source: InterPro
  5. endonuclease activity Source: UniProtKB-KW
  6. exoribonuclease activity, producing 5'-phosphomonoesters Source: InterPro
  7. helicase activity Source: UniProtKB-KW
  8. methyltransferase activity Source: InterPro
  9. omega peptidase activity Source: InterPro
  10. zinc ion binding Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. induction by virus of catabolism of host mRNA Source: UniProtKB-KW
  2. induction by virus of host autophagy Source: UniProtKB-KW
  3. modulation by virus of host protein ubiquitination Source: UniProtKB-KW
  4. suppression by virus of host ISG15 activity Source: UniProtKB-KW
  5. suppression by virus of host translation Source: UniProtKB-KW
  6. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  7. transcription, DNA-templated Source: InterPro
  8. viral RNA genome replication Source: InterPro
  9. viral protein processing Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Exonuclease, Helicase, Hydrolase, Nuclease, Nucleotidyltransferase, Protease, RNA-directed RNA polymerase, Thiol protease, Transferase

Keywords - Biological processi

Activation of host autophagy by virus, Decay of host mRNAs by virus, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host ISG15 by virus, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway, Viral immunoevasion, Viral RNA replication

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Replicase polyprotein 1ab
Short name:
pp1ab
Alternative name(s):
ORF1ab polyprotein
Cleaved into the following 15 chains:
Non-structural protein 1
Short name:
nsp1
Alternative name(s):
p28
Non-structural protein 2
Short name:
nsp2
Alternative name(s):
p65
Alternative name(s):
PL1-PRO/PL2-PRO
PL1/PL2
Papain-like proteinases 1/2
p210
Non-structural protein 4
Short name:
nsp4
Alternative name(s):
Peptide HD2
p44
3C-like proteinase (EC:3.4.22.-)
Short name:
3CL-PRO
Short name:
3CLp
Alternative name(s):
M-PRO
nsp5
p27
Non-structural protein 6
Short name:
nsp6
Non-structural protein 7
Short name:
nsp7
Alternative name(s):
p10
Non-structural protein 8
Short name:
nsp8
Alternative name(s):
p22
Non-structural protein 9
Short name:
nsp9
Alternative name(s):
p12
Non-structural protein 10
Short name:
nsp10
Alternative name(s):
Growth factor-like peptide
Short name:
GFL
p15
RNA-directed RNA polymerase (EC:2.7.7.48)
Short name:
Pol
Short name:
RdRp
Alternative name(s):
nsp12
p100
Helicase (EC:3.6.4.12, EC:3.6.4.13)
Short name:
Hel
Alternative name(s):
nsp13
p67
Exoribonuclease (EC:3.1.13.-)
Short name:
ExoN
Alternative name(s):
nsp14
Alternative name(s):
NendoU
nsp15
p35
Alternative name(s):
nsp16
Gene namesi
Name:rep
ORF Names:1a-1b
OrganismiMurine coronavirus (strain JHM) (MHV-JHM) (Murine hepatitis virus)
Taxonomic identifieri11144 [NCBI]
Taxonomic lineageiVirusesssRNA positive-strand viruses, no DNA stageNidoviralesCoronaviridaeCoronavirinaeBetacoronavirus
Virus hostiMus musculus (Mouse) [TaxID: 10090]
ProteomesiUP000007193: Genome

Subcellular locationi

Chain Non-structural protein 3 : Host membrane; Multi-pass membrane protein Reviewed prediction 1 Publication
Chain Non-structural protein 4 : Host membrane; Multi-pass membrane protein Reviewed prediction 1 Publication
Chain Non-structural protein 6 : Host membrane; Multi-pass membrane protein Reviewed prediction 1 Publication
Chain Non-structural protein 7 : Host cytoplasmhost 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.1 Publication
Chain Non-structural protein 8 : Host cytoplasmhost 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.1 Publication
Chain Non-structural protein 9 : Host cytoplasmhost 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.1 Publication
Chain Non-structural protein 10 : Host cytoplasmhost 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.1 Publication
Chain Helicase : Host endoplasmic reticulum-Golgi intermediate compartment Reviewed prediction
Note: The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA By similarity.1 Publication
Chain Uridylate-specific endoribonuclease : Host cytoplasmhost perinuclear region By similarity 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei2228 – 224821Helical; Reviewed prediction
Add
BLAST
Transmembranei2289 – 230921Helical; Reviewed prediction
Add
BLAST
Transmembranei2320 – 234021Helical; Reviewed prediction
Add
BLAST
Transmembranei2403 – 242321Helical; Reviewed prediction
Add
BLAST
Transmembranei2445 – 246521Helical; Reviewed prediction
Add
BLAST
Transmembranei2846 – 286621Helical; Reviewed prediction
Add
BLAST
Transmembranei3099 – 311921Helical; Reviewed prediction
Add
BLAST
Transmembranei3121 – 314121Helical; Reviewed prediction
Add
BLAST
Transmembranei3153 – 317321Helical; Reviewed prediction
Add
BLAST
Transmembranei3180 – 320021Helical; Reviewed prediction
Add
BLAST
Transmembranei3205 – 322521Helical; Reviewed prediction
Add
BLAST
Transmembranei3648 – 366821Helical; Reviewed prediction
Add
BLAST
Transmembranei3678 – 369821Helical; Reviewed prediction
Add
BLAST
Transmembranei3705 – 372521Helical; Reviewed prediction
Add
BLAST
Transmembranei3748 – 376821Helical; Reviewed prediction
Add
BLAST
Transmembranei3775 – 379521Helical; Reviewed prediction
Add
BLAST
Transmembranei3802 – 382221Helical; Reviewed prediction
Add
BLAST
Transmembranei3846 – 386621Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. host cell endoplasmic reticulum-Golgi intermediate compartment Source: UniProtKB-SubCell
  2. host cell membrane Source: UniProtKB-SubCell
  3. host cell perinuclear region of cytoplasm Source: UniProtKB-SubCell
  4. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2835 – 28351F → A: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2836 – 28361S → A: No effect. 1 Publication
Mutagenesisi2837 – 28371L → A: No effect. 1 Publication
Mutagenesisi2838 – 28381K → A: No effect. 1 Publication
Mutagenesisi2838 – 28381K → N: No effect. 1 Publication
Mutagenesisi2839 – 28391G → A: Partial processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2839 – 28391G → N: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2839 – 28391G → V: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2840 – 28401G → A: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2840 – 28401G → N: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2840 – 28401G → V: No processing between p210 and peptide HD2. 1 Publication
Mutagenesisi2841 – 28411A → N: No effect. 1 Publication
Mutagenesisi2842 – 28421V → N or M: No effect. 1 Publication
Mutagenesisi2846 – 28461V → M: No effect. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 247247Non-structural protein 1 Inferred
PRO_0000037354Add
BLAST
Chaini248 – 832585Non-structural protein 2 Inferred
PRO_0000037355Add
BLAST
Chaini833 – 28402008Non-structural protein 3 Inferred
PRO_0000037356Add
BLAST
Chaini2841 – 3336496Non-structural protein 4 Inferred
PRO_0000037357Add
BLAST
Chaini3337 – 36393033C-like proteinase Inferred
PRO_0000037358Add
BLAST
Chaini3640 – 3927288Non-structural protein 6 Inferred
PRO_0000037359Add
BLAST
Chaini3928 – 401992Non-structural protein 7 Inferred
PRO_0000037360Add
BLAST
Chaini4020 – 4213194Non-structural protein 8
PRO_0000037361Add
BLAST
Chaini4214 – 4323110Non-structural protein 9 Inferred
PRO_0000037362Add
BLAST
Chaini4324 – 4460137Non-structural protein 10 Inferred
PRO_0000037363Add
BLAST
Chaini4461 – 5388928RNA-directed RNA polymerase Inferred
PRO_0000037364Add
BLAST
Chaini5389 – 5988600Helicase Inferred
PRO_0000037365Add
BLAST
Chaini5989 – 6507519Exoribonuclease By similarity
PRO_0000037366Add
BLAST
Chaini6508 – 6881374Uridylate-specific endoribonuclease By similarity
PRO_0000037367Add
BLAST
Chaini6882 – 7180299Putative 2'-O-methyl transferase By similarity
PRO_0000037368Add
BLAST

Post-translational modificationi

Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed By similarity.

Interactioni

Subunit structurei

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.

Structurei

3D structure databases

ProteinModelPortaliP0C6Y0.
SMRiP0C6Y0. Positions 4055-4205, 4329-4453, 6508-6876.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1083 – 1320238Peptidase C16 1
Add
BLAST
Domaini1321 – 1481161Macro
Add
BLAST
Domaini1677 – 1936260Peptidase C16 2
Add
BLAST
Domaini3337 – 3639303Peptidase C30
Add
BLAST
Domaini5068 – 5230163RdRp catalytic
Add
BLAST
Domaini5389 – 547284CV MBD
Add
BLAST
Domaini5644 – 5825182(+)RNA virus helicase ATP-binding
Add
BLAST
Domaini5826 – 6003178(+)RNA virus helicase C-terminal
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2228 – 2465238HD1
Add
BLAST
Regioni2846 – 3225380HD2
Add
BLAST
Regioni3648 – 3866219HD3
Add
BLAST

Domaini

The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.

Sequence similaritiesi

Contains 1 Macro domain.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix, Zinc-finger

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027351. (+)RNA_virus_helicase_core_dom.
IPR022570. Coronavirus_NSP1.
IPR009461. Coronavirus_NSP16.
IPR027352. CV_MBD_dom.
IPR002589. Macro_dom.
IPR009466. NSP11.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR027417. P-loop_NTPase.
IPR002705. Pept_C30/C16_B_coronavir.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009469. RNA_pol_N_coronovir.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR029063. SAM-dependent_MTases-like.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view]
PfamiPF06478. Corona_RPol_N. 1 hit.
PF11963. DUF3477. 2 hits.
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.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF00680. RdRP_1. 1 hit.
PF08715. Viral_protease. 1 hit.
[Graphical view]
SMARTiSM00506. A1pp. 1 hit.
[Graphical view]
SUPFAMiSSF101816. SSF101816. 1 hit.
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 2 hits.
PROSITEiPS51653. CV_MBD. 1 hit.
PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by ribosomal frameshifting. Align

Isoform Replicase polyprotein 1ab (identifier: P0C6Y0-1) [UniParc]FASTAAdd to Basket

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.

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MAKMGKYGLG FKWAPEFPWM LPNASEKLGN PERSEEDGFC PSAAQEPKVK     50
GKTLVNHVRV DCSRLPALEC CVQSAIIRDI FVDEDPQKVE ASTMMALQFG 100
SAVLVKPSKR LSVQAWAKLG VLPKTPAMGL FKRFCLCNTR ECVCDAHVAF 150
QLFTVQPDGV CLGNGRFIGW FVPVTAIPEY AKQWLQPWSI LLRKGGNKGS 200
VTSGHFRRAV TMPVYDFNVE DACEEVHLNP RGKYSCKAYA LLRGYRGVKP 250
ILFVDQYGCD YTGCLAKGLE DYGDLTLSEM KELSPVWRDS LDNEVVVAWH 300
VDRDPRAVMR LQTLATVRSI EYVGQPIEDM VDGDVVMREP AHLLAPNAIV 350
KRLPRLVETM LYTDSSVTEF CYKTKLCDCG FITQFGYVDC CGDTCGFRGW 400
VPGNMMDGFP CPGCCKSYMP WELEAQSSGV IPEGGVLFTQ STDTVNRESF 450
KLYGHAVVPF GGAAYWSPYP GMWLPVIWSS VKSYSYLTYT GVVGCKAIVQ 500
ETDAICRFLY MDYVQHKCGN LEQRAILGLD DVYHRQLLVN RGDYSLLLEN 550
VDLFVKRRAE FACKFATCGD GLVPLLLDGL VPRSYYLIKS GQAFTSLMVN 600
FSREVVDMCM DMALLFMHDV KVATKYVKKV TGKVAVRFKA LGIAVVRKIT 650
EWFDLAVDTA ASAAGWLCYQ LVNGLFAVAN GVITFIQEVP ELVKNFVDKF 700
KTFFKVLIDS MSVSILSGLT VVKTASNRVC LAGSKVYEVV QKSLPAYIMP 750
VGCSEATCLV GEIEPAVFED DVVDVVKAPL TYQGCCKPPS SFEKICIVDK 800
LYMAKCGDQF YPVVVDNDTV GVLDQCWRFP CAGKKVVFND KPKVKEVPST 850
RKIKIIFALD ATFDSVLSKA CSEFEVDKDV TLDELLDVVL DAVESTLSPC 900
KEHGVIGTKV CALLERLVDD YVYLFDEGGE EVIASRMYCS FSAPDEDCVA 950
TDVVYADENQ DDDADDPVVL VADTQEEDGV AREQVDSADS EICVAHTGGQ 1000
EMTEPDVVGS QTPIASAEET EVGEACDREG IAEVKATVCA DALDACPDQV 1050
EAFDIEKVED SILSELQTEL NAPADKTYED VLAFDAIYSE TLSAFYAVPS 1100
DETHFKVCGF YSPAIERTNC WLRSTLIVMQ SLPLEFKDLG MQKLWLSYKA 1150
GYDQCFVDKL VKSAPKSIIL PQGGYVADFA YFFLSQCSFK VHANWRCLKC 1200
GMELKLQGLD AVFFYGDVVS HMCKCGNSMT LLSADIPYTF DFGVRDDKFC 1250
AFYTPRKVFR AACAVDVNDC HSMAVVDGKQ IDGKVVTKFN GDKFDFMVGH 1300
GMTFSMSPFE IAQLYGSCIT PNVCFVKGDV IKVLRRVGAE VIVNPANGRM 1350
AHGAGVAGAI AKAAGKAFIN ETADMVKAQG VCQVGGCYES TGGKLCKKVL 1400
NIVGPDARGH GNECYSLLER AYQHINKCDN VVTTLISAGI FSVPTDVSLT 1450
YLLGVVTKNV ILVSNNQDDF DVIEKCQVTS VAGTKALSFQ LAKNLCRDVK 1500
FVTNACSSLF SESSFVSSYD VLQEVEALRH DIQLDDDARV FVQANMDCLP 1550
TDWRLVNKFD SVDGVRTIKY FECPGEVFVS SQGKKFGYVQ NGSFKEASVS 1600
QIRALLANKV DVLCTVDGVN FRSCCVAEGE VFGKTLGSVF CDGINVTKVR 1650
CSAIHKGKVF FQYSGLSAAD LAAVKDAFGF DEPQLLQYYS MLGMCKWPVV 1700
VCGNYFAFKQ SNNNCYINVA CLMLQHLSLK FPKWQWRRPG NEFRSGKPLR 1750
FVSLVLAKGS FKFNEPSDST DFIRVELREA DLSGATCDLE FICKCGVKQE 1800
QRKGVDAVMH FGTLDKSGLV KGYNIACTCG DKLVHCTQFN VPFLICSNTP 1850
EGKKLPDDVV AANIFTGGSV GHYTHVKCKP KYQLYDACNV SKVSEAKGNF 1900
TDCLYLKNLK QTFSSVLTTY YLDDVKCVAY KPDLSQYYCE SGKYYTKPII 1950
KAQFRTFEKV EGVYTNFKLV GHDIAEKLNA KLGFDCNSPF MEYKITEWPT 2000
ATGDVVLASD DLYVSRYSGG CVTFGKPVIW RGHEEASLKS LTYFNRPSVV 2050
CENKFNVLPV DVSEPTDRRP VPSAVLVTGA ASGADASAIS TEPGTAKEQK 2100
ACASDSVEDQ IVMEAQKKSS VTTVAVKEVK LNGVKKPVKW NCSVVVNDPT 2150
SETKVVKSLS IVDVYDMFLT GCRYVVWTAN ELSRLINSPT VREYVKWGMS 2200
KLIIPANLLL LRDEKQEFVA PKVVKAKAIA CYGAVKWFLL YCFSWIKFNT 2250
DNKVIYTTEV ASKLTFKLCC LAFKNALQTF NWSVVSRGFF LVATVFLLWF 2300
NFLYANVILS DFYLPNIGPL PMFVGQIVAW VKTTFGVLTI CDFYQVTDLG 2350
YRSSFCNGSM VCELCFSGFD MLDNYESINV VQHVVDRRVS FDYISLFKLV 2400
VELVIGYSLY TVCFYPLFVL VGMQLLTTWL PEFFMLGTMH WSARLFVFVA 2450
NMLPAFTLLR FYIVVTAMYK VYCLCRHVMY GCSKPGCLFC YKRNRSVRVK 2500
CSTVVGGSLR YYDVMANGGT GFCTKHQWNC LNCNSWKPGN TFITHEAAAD 2550
LSKELKRPVN PTDSAYYSVI EVKQVGCSMR LFYERDGQRV YDDVSASLFV 2600
DMNGLLHSKV KGVPETHVVV VENEADKAGF LNAAVFYAQS LYRPMLMVEK 2650
KLITTANTGL SVSRTMFDLY VYSLLRHLDV DRKSLTSFVN AAHNSLKEGV 2700
QLEQVMDTFV GCARRKCAID SDVETKSITK SVMAAVNAGV EVTDESCNNL 2750
VPTYVKSDTI VAADLGVLIQ NNAKHVQSNV AKAANVACIW SVDAFNQLSA 2800
DLQHRLRKAC VKTGLKIKLT YNKQEANVPI LTTPFSLKGG AVFSRVLQWL 2850
FVANLICFIV LWALMPTYAV HKSDMQLPLY ASFKVIDNGV LRDVSVTDAC 2900
FANKFNQFDQ WYESTFGLVY YRNSKACPVV VAVIDQDIGH TLFNVPTKVL 2950
RYGFHVLHFI THAFATDRVQ CYTPHMQIPY DNFYASGCVL SSLCTMLAHA 3000
DGTPHPYCYT EGVMHNASLY SSLVPHVRYN LASSNGYIRF PEVVSEGIVR 3050
VVRTRSMTYC RVGLCEEAEE GICFNFNSSW VLNNPYYRAM PGTFCGRNAF 3100
DLIHQVLGGL VQPIDFFALT ASSVAGAILA IIVVLAFYYL IKLKRAFGDY 3150
TSVVVINVIV WCINFLMLFV FQVYPTLSCL YACFYFYTTL YFPSEISVVM 3200
HLQWLVMYGA IMPLWFCITY VAVVVSNHAL WLFSYCRKIG TDVRSDGTFE 3250
EMALTTFMIT KESYCKLKNS VSDVAFNRYL SLYNKYRYFS GKMDTATYRE 3300
AACSQLAKAM ETFNHNNGND VLYQPPTASV TTSFLQSGIV KMVSPTSKVE 3350
PCVVSVTYGN MTLNGLWLDD KVYCPRHVIC SSADMTDPDY PNLLCRVTSS 3400
DFCVMSDRMS LTVMSYQMQG SLLVLTVTLQ NPNTPKYSFG VVKPGETFTV 3450
LAAYNGRPQG AFHVVMRSSH TIKGSFLCGS CGSVGYVLTG DSVRFVYMHQ 3500
LELSTGCHTG TDFSGNFYGP YRDAQVVQLP VQDYTQTVNV VAWLYAAILN 3550
RCNWFVQSDS CSLEEFNVWA MTNGFSSIKA DLVLDALASM TGVTVEQVLA 3600
AIKRLHSGFQ GKQILGSCVL EDELTPSDVY QQLAGVKLQS KRTRVIKGTC 3650
CWILASTFLF CSIISAFVKW TMFMYVTTHM LGVTLCALCF VIFAMLLIKH 3700
KHLYLTMYIM PVLCTLFYTN YLVVGYKQSF RGLAYAWLSY FVPAVDYTYM 3750
DEVLYGVVLL VAMVFVTMRS INHDVFSTMF LVGRLVSLVS MWYFGANLEE 3800
EVLLFLTSLF GTYTWTTMLS LATAKVIAKW LAVNVLYFTD IPQIKLVLLS 3850
YLCIGYVCCC YWGVLSLLNS IFRMPLGVYN YKISVQELRY MNANGLRPPR 3900
NSFEALMLNF KLLGIGGVPV IEVSQIQSRL TDVKCANVVL LNCLQHLHIA 3950
SNSKLWQYCS TLHNEILATS DLSVAFDKLA QLLVVLFANP AAVDSKCLAS 4000
IEEVSDDYVR DNTVLQALQS EFVNMASFVE YELAKKNLDE AKASGSANQQ 4050
QIKQLEKACN IAKSAYERDR AVARKLERMA DLALTNMYKE ARINDKKSKV 4100
VSALQTMLFS MVRKLDNQAL NSILDNAVKG CVPLNAIPPL TSNTLTIIVP 4150
DKQVFDQVVD NVYVTYAPNV WHIQSIQDAD GAVKQLNEID VNSTWPLVIS 4200
ANRHNEVSTV VLQNNELMPQ KLRTQVVNSG SDMNCNIPTQ CYYNTTGTGK 4250
IVYAILSDCD GLKYTKIVKE DGNCVVLELD PPCKFSVQDV KGLKIKYLYF 4300
VKGCNTLARG WVVGTLSSTV RLQAGTATEY ASNSAILSLC AFSVDPKKTY 4350
LDYIQQGGVP VTNCVKMLCD HAGTGMAITI KPEATTNQDS YGGASVCIYC 4400
RSRVEHPDVD GLCKLRGKFV QVPLGIKDPV SYVLTHDVCQ VCGFWRDGSC 4450
SCVGTGSQFQ SKDTNFLNRV RGTSVNARLV PCASGLDTDV QLRAFDICNA 4500
NRAGIGLYYK VNCFRFQRVD EEGNKLDKFF VVKRTNLEVY NKEKECYELT 4550
KDCGVVAEHE FFTFDVEGSR VPHIVRKDLS KFTMLDLCYA LRHFDRNDCS 4600
TLKEILLTYA ECDESYFQKK DWYDFVENPD IINVYKKLGP IFNRALLNTA 4650
NFADTLVEAG LVGVLTLDNQ DLYGQWYDFG DFVKTVPCCG VAVADSYYSY 4700
MMPMLTMCHA LDSELFVNGT YREFDLVQYD FTDFKLELFN KYFKHWSMTY 4750
HPNTSECEDD RCIIHCANFN ILFSMVLPKT CFGPLVRQIF VDGVPFVVSI 4800
GYHYKELGVV MNMDVDTHRY RLSLKDLLLY AADPALHVAS ASALLDLRTC 4850
CFSVAAITSG VKFQTVKPGN FNQDFYEFIL SKGLLKEGSS VDLKHFFFTQ 4900
DGNAAITDYN YYKYNLPTMV DIKQLLFVVE VVNKYFEIYE GGCIPATQVI 4950
VNNYDKSAGY PFNKFGKARL YYEALSFEEQ DEIYAYTKRN VLPTLTQMNL 5000
KYAISAKNRA RTVAGVSILS TMTGRMFHQK CLKSIAATRG VPVVIGTTKF 5050
YGGWDDMLRR LIKDVDSPVL MGWDYPKCDR AMPNILRIVS SLVLARKHDS 5100
CCSHTDRFYR LANECAQVLG EIVMCGGCYY VKPGGTSSGD ATTAFANSVF 5150
NICQAVSANV CSLMACNGHK IEDLSIRELQ KRLYSNVYRA DHVDPAFVSE 5200
YYEFLNKHFS MIILSDDGVV CYNSEFASKG YIANISDFQQ VLYYQNNVFM 5250
SEAKCWVETD IEKGPHEFCS QHTMLVKMDG DEVYLPYPDP SRILGAGCFV 5300
DDLLKTDSVL LIERFVSLAI DAYPLVYHEN PEYQNVFRVY LEYIKKLYND 5350
LGNQILDSIS VILSTCDGQK FTDETFYKNM YLRSAVMQSV GACVVCSSQT 5400
SLRCGSCIRK PLLCCKCAYD HVMSTDHKYV LSVSPYVCNS PGCDVNDVTK 5450
LYLGGMSYYC EAHKPQYSFK LVMNGMVFGL YKQSCTGSPY IEDFNKIASC 5500
KWTEVDDYVL ANECTERLKL FAAETQKATE EAFKQCYASA TIREIVSDRE 5550
LILSWEIGKV RPPLNKNYVF TGYHFTNNGK TVLGEYVFDK SELTNGVYYR 5600
ATTTYKLSVG DVFILTSHAV SSLSAPTLVP QENYTSVRFA SAYSVPETFQ 5650
NNVPNYQHIG IKRYCTVQGP PGTGKSHLAI GHAVYYCTAR VVYTAASHAA 5700
VDALCEKAHK FLNINDCARI VPAKLRVDCY DKFNVNDTTR KYVFTTINAL 5750
PELVTDIIVV DEVSMLTNYE LSVINSRVRA KHYVYIGDPA QLPAPRVLLN 5800
KGTLEPRYFN SVTKLMCCLG PDIFLGTCYR CPKEIVDTVS ALVYNNKLKA 5850
KNDNSAMCFK VYYKGQTTHE SSSAVNMQQI HLISKLLKAN PSWSNAVFIS 5900
PYNSQNYVAK RVLGLQTQTA DSAQGSAYDF VIYSQTAQTA HSVNVNRFNV 5950
AITRAKKGIL CVMSSMQLIG VFNFTTLTLD KINNPRLQCT TNLFKDCSKS 6000
YVGIPPCAFL LAVDDKYKVS GNLAVCLNVA DSAVTYSRLI SLMGFKLDLT 6050
LDGYCKLFIT RDEAIKRVRA WVGFDAEGAH ATRDSIGTNF PLQLGFSTGI 6100
DFVVEATGMF AERDGYVFKK AAARAPPGEQ FKHLVPLMSR GQKWDVVRIR 6150
IVQMLSDHLV DLADSVVLVT WAASFELTCL RYFAKVGKEV VCSVCNKRAT 6200
CFNSRTGYYG CWRHSYSCDY LYNPLIVDIQ QWGYTGSLTS NHDPICSVHK 6250
GAHVASSDAI MTRCLAVHDC FCKSVNWNLE YPIISNEVSV NTSCRLLQRV 6300
MFRAAMLCNR YDVCYDIGNP KGLACVKGYD FKFYDASPVV KSVKQFVYKY 6350
EAHKDQFLDG LCMFWNCNVD KYPANAVVCR FDTRVLSKLN LPGCNGGSLY 6400
VNKHAFHTNP FTRAAFENLK PMPFFYYSDT PCVYMEGMES KQVDYVPLRS 6450
ATCITRCNLG GAVCLKHAEE YREYLESYNT ATTAGFTFWV YKTFDFYNLW 6500
NTFTRLQSLE NVVYNLVNAG HFDGRAGELP CAVIGEKVIA KIQNEDVVVF 6550
KNNTPFPTNV AVELFAERSI RPHPELKLFR SSNIHVCWNH VLWDYAKDSV 6600
FCSSTYKVCK YTDLQCIESL NVLFDGRDNG ALEAFKKCRN GVYINTTKIK 6650
SLSMIKGPQR ADLNGVVVEK VGDSDVEFWF AMRRDGDDVI FSRTGSLEPS 6700
HYRSPQGNPG GNRVGDLSGN EALARGTIFT QSRFLSSFSP RSEMEKDFMD 6750
LDEDVFIAKY SLQDYAFEHV VYGSFNQKII GGLHLLIGLA RRPKKSNLVI 6800
QEFVPYDSSI HSYFITDENS GSSESVCTVI DLLLDDFVDI VKSLNLKCVS 6850
KVVNVNVDFK DFQFMLWCNE EKVMTFYPRL QAAADWKPGY VMPVLYKYLE 6900
SPMERVNLWN YGKPITLPTG CMMNVAKYTQ LCQYLSTTTL AVPANMRVLH 6950
LGAGSDKGVA PGSAVLRQWL PSGSILVDND MNPFVSDSVA SYYGNCITLP 7000
FDCQWDLIIS DMYDPLTKNI GEYNVSKDGF FTYLCHLIRD KLALGGSVAI 7050
KITEFSWNAE LYSLMGKFAF WTIFCTNVNA SSSEGFLIGI NWLNRTRNEI 7100
DGKTMHANYL FWRNSTMWNG GAYSLFDMTK FPLKAAGTAV VSLKPDQIND 7150
LVLSLIEKGK LLVRDTRKEV FVGDSLVNVK 7180

Note: Produced by -1 ribosomal frameshifting at the 1a-1b genes boundary.

Length:7,180
Mass (Da):803,440
Last modified:June 10, 2008 - v1
Checksum:i313A78E1CC87B347
GO
Isoform Replicase polyprotein 1a (identifier: P0C6V1-1) [UniParc]FASTAAdd to Basket

Also known as: pp1a, ORF1a polyprotein

The sequence of this isoform can be found in the external entry P0C6V1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by conventional translation.

Length:4,474
Mass (Da):497,595
GO

Sequence cautioni

The sequence AAA46457.1 differs from that shown. Reason: Frameshift at positions 690, 915, 1529, 2069 and 3316.
The sequence AAA46457.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence AAA46458.2 differs from that shown. Reason: Erroneous gene model prediction.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M55148 Genomic RNA. Translation: AAA46457.1. Sequence problems.
M55148 Genomic RNA. Translation: AAA46458.2. Sequence problems.
M18040 Genomic RNA. Translation: AAA46466.1.
S51684 Genomic RNA. Translation: AAB19566.1.
PIRiA36815. RRIHM2.
B36815. VFIHJH.
RefSeqiYP_209229.2. AC_000192.1. [P0C6Y0-1]

Keywords - Coding sequence diversityi

Ribosomal frameshifting

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M55148 Genomic RNA. Translation: AAA46457.1 . Sequence problems.
M55148 Genomic RNA. Translation: AAA46458.2 . Sequence problems.
M18040 Genomic RNA. Translation: AAA46466.1 .
S51684 Genomic RNA. Translation: AAB19566.1 .
PIRi A36815. RRIHM2.
B36815. VFIHJH.
RefSeqi YP_209229.2. AC_000192.1. [P0C6Y0-1 ]

3D structure databases

ProteinModelPortali P0C6Y0.
SMRi P0C6Y0. Positions 4055-4205, 4329-4453, 6508-6876.
ModBasei Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR027351. (+)RNA_virus_helicase_core_dom.
IPR022570. Coronavirus_NSP1.
IPR009461. Coronavirus_NSP16.
IPR027352. CV_MBD_dom.
IPR002589. Macro_dom.
IPR009466. NSP11.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR027417. P-loop_NTPase.
IPR002705. Pept_C30/C16_B_coronavir.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009469. RNA_pol_N_coronovir.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR029063. SAM-dependent_MTases-like.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view ]
Pfami PF06478. Corona_RPol_N. 1 hit.
PF11963. DUF3477. 2 hits.
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.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF00680. RdRP_1. 1 hit.
PF08715. Viral_protease. 1 hit.
[Graphical view ]
SMARTi SM00506. A1pp. 1 hit.
[Graphical view ]
SUPFAMi SSF101816. SSF101816. 1 hit.
SSF144246. SSF144246. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF53335. SSF53335. 2 hits.
PROSITEi PS51653. CV_MBD. 1 hit.
PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase."
    Lee H.-J., Shieh C.-K., Gorbalenya A.E., Koonin E.V., la Monica N., Tuler J., Bagdzhardzhyan A., Lai M.M.C.
    Virology 180:567-582(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Sequence and translation of the murine coronavirus 5'-end genomic RNA reveals the N-terminal structure of the putative RNA polymerase."
    Soe L.H., Shieh C.-K., Baker S.C., Chang M.F., Lai M.M.C.
    J. Virol. 61:3968-3976(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-595.
  3. "Mouse hepatitis virus strain A59 RNA polymerase gene ORF 1a: heterogeneity among MHV strains."
    Bonilla P.J., Gorbalenya A.E., Weiss S.R.
    Virology 198:736-740(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION.
  4. "Murine coronavirus gene 1 polyprotein contains an autoproteolytic activity."
    Baker S.C., La Monica N., Shieh C.K., Lai M.M.
    Adv. Exp. Med. Biol. 276:283-289(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1021-1326.
  5. "Identification of the murine coronavirus MP1 cleavage site recognized by papain-like proteinase 2."
    Kanjanahaluethai A., Jukneliene D., Baker S.C.
    J. Virol. 77:7376-7382(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF PHE-2835; SER-2836; LEU-2837; LYS-2838; GLY-2839; GLY-2840; ALA-2841; VAL-2842 AND VAL-2846.
  6. "Processing of the coronavirus MHV-JHM polymerase polyprotein: identification of precursors and proteolytic products spanning 400 kilodaltons of ORF1a."
    Schiller J.J., Kanjanahaluethai A., Baker S.C.
    Virology 242:288-302(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, SUBCELLULAR LOCATION.
  7. "Conservation of substrate specificities among coronavirus main proteases."
    Hegyi A., Ziebuhr J.
    J. Gen. Virol. 83:595-599(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.

Entry informationi

Entry nameiR1AB_CVMJH
AccessioniPrimary (citable) accession number: P0C6Y0
Secondary accession number(s): P19751
, P29982, Q66194, Q90045
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: September 3, 2014
This is version 55 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi