P0C6X9 (R1AB_CVMA5) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Replicase polyprotein 1ab
Short name=pp1ab

Alternative name(s):
ORF1ab polyprotein

Cleaved into the following 15 chains:

1. Non-structural protein 1
   Short name=nsp1
   Alternative name(s):
   p28
2. Non-structural protein 2
   Short name=nsp2
   Alternative name(s):
   p65
3. Non-structural protein 3
   Short name=nsp3
   EC=3.4.19.12
   EC=3.4.22.69
   Alternative name(s):
   PL1-PRO/PL2-PRO
   PL1/PL2
   Papain-like proteinases 1/2
   p210
4. Non-structural protein 4
   Short name=nsp4
   Alternative name(s):
   Peptide HD2
   p44
5. 3C-like proteinase
   Short name=3CL-PRO
   Short name=3CLp
   EC=3.4.22.-
   Alternative name(s):
   M-PRO
   nsp5
   p27
6. Non-structural protein 6
   Short name=nsp6
7. Non-structural protein 7
   Short name=nsp7
   Alternative name(s):
   p10
8. Non-structural protein 8
   Short name=nsp8
   Alternative name(s):
   p22
9. Non-structural protein 9
   Short name=nsp9
   Alternative name(s):
   p12
10. Non-structural protein 10
    Short name=nsp10
    Alternative name(s):
    Growth factor-like peptide
    Short name=GFL
    p15
11. RNA-directed RNA polymerase
    Short name=Pol
    Short name=RdRp
    EC=2.7.7.48
    Alternative name(s):
    nsp12
    p100
12. Helicase
    Short name=Hel
    EC=3.6.4.12
    EC=3.6.4.13
    Alternative name(s):
    nsp13
    p67
13. Exoribonuclease
    Short name=ExoN
    EC=3.1.13.-
    Alternative name(s):
    nsp14
14. Uridylate-specific endoribonuclease
    EC=3.1.-.-
    Alternative name(s):
    NendoU
    nsp15
    p35
15. Putative 2'-O-methyl transferase
    EC=2.1.1.-
    Alternative name(s):
    nsp16

Gene names

Name:	rep
ORF Names:	1a-1b

Organism

Murine coronavirus (strain A59) (MHV-A59) (Murine hepatitis virus) [Reference proteome]

Taxonomic identifier

11142 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Betacoronavirus › Murine coronavirus › Murine hepatitis virus

Virus host

Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	7176 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Catalytic activity	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).
Subunit structure	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.
Subcellular location	Non-structural protein 3: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 4: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 6: Host membrane; Multi-pass membrane protein Potential Ref.6. Non-structural protein 7: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. Ref.6 Non-structural protein 8: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. Ref.6 Non-structural protein 9: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. Ref.6 Non-structural protein 10: Host cytoplasm › host perinuclear region By similarity Ref.6. Note: nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. Ref.6 Helicase: Host endoplasmic reticulum-Golgi intermediate compartment Potential. Note: The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. Ref.6 Uridylate-specific endoribonuclease: Host cytoplasm › host perinuclear region By similarity Ref.6.
Domain	The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane.
Post-translational modification	Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed By similarity.
Sequence similarities	Belongs to the coronaviruses polyprotein 1ab family. Contains 1 (+)RNA virus helicase ATP-binding domain. Contains 1 (+)RNA virus helicase C-terminal domain. Contains 1 CV MBD (coronavirus metal-binding) domain. Contains 1 Macro domain. Contains 2 peptidase C16 domains. Contains 1 peptidase C30 domain. Contains 1 RdRp catalytic domain.
Sequence caution	The sequence AAB86818.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAB86820.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAA36202.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Activation of host autophagy by virus Host-virus interaction Inhibition of host ISG15 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Modulation of host ubiquitin pathway by viral deubiquitinase Modulation of host ubiquitin pathway by virus Ubl conjugation pathway Viral RNA replication Viral immunoevasion
Cellular component	Host cytoplasm Host membrane Membrane
Coding sequence diversity	Ribosomal frameshifting
Domain	Repeat Transmembrane Transmembrane helix Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding Zinc
Molecular function	Endonuclease Exonuclease Helicase Hydrolase Nuclease Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	induction by virus of host autophagy Inferred from electronic annotation. Source: UniProtKB-KW methylation Inferred from electronic annotation. Source: GOC modulation by virus of host protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC proteolysis Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host ISG15 activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro viral protein processing Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell endoplasmic reticulum-Golgi intermediate compartment Inferred from electronic annotation. Source: UniProtKB-SubCell host cell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW exoribonuclease activity, producing 5'-phosphomonoesters Inferred from electronic annotation. Source: InterPro helicase activity Inferred from electronic annotation. Source: UniProtKB-KW methyltransferase activity Inferred from electronic annotation. Source: InterPro omega peptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]

Isoform Replicase polyprotein 1ab (identifier: P0C6X9-1)

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.

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

Isoform Replicase polyprotein 1a (identifier: P0C6V0-1)

Also known as: pp1a; ORF1a polyprotein;

The sequence of this isoform can be found in the external entry P0C6V0.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by conventional translation.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 247

247

Non-structural protein 1 Probable

PRO_0000037338

Chain

248 – 832

585

Non-structural protein 2 Probable

PRO_0000037339

Chain

833 – 2837

2005

Non-structural protein 3 Probable

PRO_0000037340

Chain

2838 – 3333

496

Non-structural protein 4

PRO_0000037341

Chain

3334 – 3635

302

3C-like proteinase

PRO_0000037342

Chain

3636 – 3921

286

Non-structural protein 6 Probable

PRO_0000037343

Chain

3922 – 4013

92

Non-structural protein 7

PRO_0000037344

Chain

4014 – 4207

194

Non-structural protein 8

PRO_0000037345

Chain

4208 – 4317

110

Non-structural protein 9

PRO_0000037346

Chain

4318 – 4454

137

Non-structural protein 10

PRO_0000037347

Chain

4455 – 5382

928

RNA-directed RNA polymerase

PRO_0000037348

Chain

5383 – 5982

600

Helicase Probable

PRO_0000037349

Chain

5983 – 6503

521

Exoribonuclease By similarity

PRO_0000037350

Chain

6504 – 6877

374

Uridylate-specific endoribonuclease By similarity

PRO_0000037351

Chain

6878 – 7176

299

Putative 2'-O-methyl transferase By similarity

PRO_0000037352

Regions

Transmembrane

2225 – 2245

21

Helical; Potential

Transmembrane

2286 – 2306

21

Helical; Potential

Transmembrane

2314 – 2334

21

Helical; Potential

Transmembrane

2400 – 2420

21

Helical; Potential

Transmembrane

2442 – 2462

21

Helical; Potential

Transmembrane

2625 – 2645

21

Helical; Potential

Transmembrane

2847 – 2867

21

Helical; Potential

Transmembrane

3096 – 3116

21

Helical; Potential

Transmembrane

3118 – 3138

21

Helical; Potential

Transmembrane

3150 – 3170

21

Helical; Potential

Transmembrane

3177 – 3197

21

Helical; Potential

Transmembrane

3202 – 3222

21

Helical; Potential

Transmembrane

3644 – 3664

21

Helical; Potential

Transmembrane

3674 – 3694

21

Helical; Potential

Transmembrane

3699 – 3719

21

Helical; Potential

Transmembrane

3742 – 3762

21

Helical; Potential

Transmembrane

3769 – 3789

21

Helical; Potential

Transmembrane

3796 – 3816

21

Helical; Potential

Transmembrane

3840 – 3860

21

Helical; Potential

Domain

1084 – 1333

250

Peptidase C16 1

Domain

1323 – 1482

160

Macro

Domain

1678 – 1937

260

Peptidase C16 2

Domain

3334 – 3635

302

Peptidase C30

Domain

5062 – 5224

163

RdRp catalytic

Domain

5383 – 5466

84

CV MBD

Domain

5638 – 5819

182

(+)RNA virus helicase ATP-binding

Domain

5820 – 5989

170

(+)RNA virus helicase C-terminal

Zinc finger

1198 – 1226

29

C4-type 1

Zinc finger

1794 – 1830

37

C4-type 2

Zinc finger

4391 – 4407

17

By similarity

Zinc finger

4433 – 4446

14

By similarity

Nucleotide binding

5663 – 5670

8

ATP By similarity

Region

2225 – 2645

421

HD1

Region

2847 – 3222

376

HD2

Region

3526 – 3860

335

HD3

Sites

Active site

1121

1

For PL1-PRO activity By similarity

Active site

1272

1

For PL1-PRO activity By similarity

Active site

1716

1

For PL2-PRO activity By similarity

Active site

1873

1

For PL2-PRO activity By similarity

Active site

3374

1

For 3CL-PRO activity By similarity

Active site

3478

1

For 3CL-PRO activity

Site

247 – 248

2

Cleavage; by PL1-PRO Probable

Site

832 – 833

2

Cleavage; by PL1-PRO Probable

Site

2837 – 2838

2

Cleavage; by PL2-PRO

Site

3333 – 3334

2

Cleavage; by 3CL-PRO

Site

3635 – 3636

2

Cleavage; by 3CL-PRO

Site

3921 – 3922

2

Cleavage; by 3CL-PRO

Site

4013 – 4014

2

Cleavage; by 3CL-PRO

Site

4207 – 4208

2

Cleavage; by 3CL-PRO

Site

4317 – 4318

2

Cleavage; by 3CL-PRO

Site

4454 – 4455

2

Cleavage; by 3CL-PRO

Site

5382 – 5383

2

Cleavage; by 3CL-PRO

Site

5982 – 5983

2

Cleavage; by 3CL-PRO Probable

Site

6503 – 6504

2

Cleavage; by 3CL-PRO Probable

Site

6877 – 6878

2

Cleavage; by 3CL-PRO Probable

Natural variations

Natural variant

1699

1

P → S in strain: Isolate C12 mutant.

Natural variant

2196

1

M → K in strain: Isolate C12 mutant.

Natural variant

5773

1

R → S in strain: Isolate C12 mutant.

Experimental info

Mutagenesis

3331

1

F → A, H or W: No effect. Ref.7

Mutagenesis

3332

1

L → I or S: No processing between peptide HD2 and 3CL-PRO. Ref.7

Mutagenesis

3333

1

Q → A, K or R: No processing between peptide HD2 and 3CL-PRO. Ref.7

Mutagenesis

3334

1

S → A: No effect. Ref.7

Mutagenesis

3334

1

S → C: No processing between peptide HD2 and 3CL-PRO. Ref.7

Mutagenesis

3335

1

G → A: No effect. Ref.7

Mutagenesis

3335

1

G → P: No processing between peptide HD2 and 3CL-PRO. Ref.7

Mutagenesis

3336

1

I → L: No effect. Ref.7

Mutagenesis

3478

1

C → A: Complete loss of 3CL-PRO activity. Ref.7

Mutagenesis

5381

1

L → I: No processing between RDRP and helicase. Ref.7

Mutagenesis

5381

1

L → M: No effect. Ref.7

Mutagenesis

5382

1

Q → K or R: No processing between RDRP and helicase. Ref.7

Mutagenesis

5383

1

S → A: No effect. Ref.7

Mutagenesis

5383

1

S → N: No processing between RDRP and helicase. Ref.7

Sequence conflict

287 – 288

2

WR → CA Ref.4

Sequence conflict

311

1

L → V Ref.4

Sequence conflict

570

1

D → G Ref.4

Sequence conflict

3620

1

E → EL Ref.3

Sequence conflict

3711

1

T → TL Ref.3

Sequence conflict

3968

1

M → V Ref.3

Sequence conflict

4464

1

I → V Ref.3

Sequence conflict

6156

1

V → A Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

7176

Helix Strand Turn

Details...

Helix

3246 – 3249

4

Beta strand

3254 – 3256

3

Helix

3258 – 3267

10

Helix

3270 – 3278

9

Helix

3280 – 3284

5

Beta strand

3287 – 3290

4

Helix

3292 – 3313

22

Beta strand

3318 – 3320

3

Beta strand

3326 – 3330

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Replicase polyprotein 1ab (pp1ab) [UniParc]. Last modified June 10, 2008. Version 1. Checksum: AE90461FA631BED3	FASTA	7,176	802,596
	10 20 30 40 50 60 MAKMGKYGLG FKWAPEFPWM LPNASEKLGN PERSEEDGFC PSAAQEPKVK GKTLVNHVRV 70 80 90 100 110 120 NCSRLPALEC CVQSAIIRDI FVDEDPQKVE ASTMMALQFG SAVLVKPSKR LSIQAWTNLG 130 140 150 160 170 180 VLPKTAAMGL FKRVCLCNTR ECSCDAHVAF HLFTVQPDGV CLGNGRFIGW FVPVTAIPEY 190 200 210 220 230 240 AKQWLQPWSI LLRKGGNKGS VTSGHFRRAV TMPVYDFNVE DACEEVHLNP KGKYSCKAYA 250 260 270 280 290 300 LLKGYRGVKP ILFVDQYGCD YTGCLAKGLE DYGDLTLSEM KELFPVWRDS LDSEVLVAWH 310 320 330 340 350 360 VDRDPRAAMR LQTLATVRCI DYVGQPTEDV VDGDVVVREP AHLLAANAIV KRLPRLVETM 370 380 390 400 410 420 LYTDSSVTEF CYKTKLCECG FITQFGYVDC CGDTCDFRGW VAGNMMDGFP CPGCTKNYMP 430 440 450 460 470 480 WELEAQSSGV IPEGGVLFTQ STDTVNRESF KLYGHAVVPF GSAVYWSPCP GMWLPVIWSS 490 500 510 520 530 540 VKSYSGLTYT GVVGCKAIVQ ETDAICRSLY MDYVQHKCGN LEQRAILGLD DVYHRQLLVN 550 560 570 580 590 600 RGDYSLLLEN VDLFVKRRAE FACKFATCGD GLVPLLLDGL VPRSYYLIKS GQAFTSMMVN 610 620 630 640 650 660 FSHEVTDMCM DMALLFMHDV KVATKYVKKV TGKLAVRFKA LGVAVVRKIT EWFDLAVDIA 670 680 690 700 710 720 ASAAGWLCYQ LVNGLFAVAN GVITFVQEVP ELVKNFVDKF KAFFKVLIDS MSVSILSGLT 730 740 750 760 770 780 VVKTASNRVC LAGSKVYEVV QKSLSAYVMP VGCSEATCLV GEIEPAVFED DVVDVVKAPL 790 800 810 820 830 840 TYQGCCKPPT SFEKICIVDK LYMAKCGDQF YPVVVDNDTV GVLDQCWRFP CAGKKVEFND 850 860 870 880 890 900 KPKVRKIPST RKIKITFALD ATFDSVLSKA CSEFEVDKDV TLDELLDVVL DAVESTLSPC 910 920 930 940 950 960 KEHDVIGTKV CALLDRLAGD YVYLFDEGGD EVIAPRMYCS FSAPDDEDCV AADVVDADEN 970 980 990 1000 1010 1020 QDDDAEDSAV LVADTQEEDG VAKGQVEADS EICVAHTGSQ EELAEPDAVG SQTPIASAEE 1030 1040 1050 1060 1070 1080 TEVGEASDRE GIAEAKATVC ADAVDACPDQ VEAFEIEKVE DSILDELQTE LNAPADKTYE 1090 1100 1110 1120 1130 1140 DVLAFDAVCS EALSAFYAVP SDETHFKVCG FYSPAIERTN CWLRSTLIVM QSLPLEFKDL 1150 1160 1170 1180 1190 1200 EMQKLWLSYK AGYDQCFVDK LVKSVPKSII LPQGGYVADF AYFFLSQCSF KAYANWRCLE 1210 1220 1230 1240 1250 1260 CDMELKLQGL DAMFFYGDVV SHMCKCGNSM TLLSADIPYT LHFGVRDDKF CAFYTPRKVF 1270 1280 1290 1300 1310 1320 RAACAVDVND CHSMAVVEGK QIDGKVVTKF IGDKFDFMVG YGMTFSMSPF ELAQLYGSCI 1330 1340 1350 1360 1370 1380 TPNVCFVKGD VIKVVRLVNA EVIVNPANGR MAHGAGVAGA IAEKAGSAFI KETSDMVKAQ 1390 1400 1410 1420 1430 1440 GVCQVGECYE SAGGKLCKKV LNIVGPDARG HGKQCYSLLE RAYQHINKCD NVVTTLISAG 1450 1460 1470 1480 1490 1500 IFSVPTDVSL TYLLGVVTKN VILVSNNQDD FDVIEKCQVT SVAGTKALSL QLAKNLCRDV 1510 1520 1530 1540 1550 1560 KFVTNACSSL FSESCFVSSY DVLQEVEALR HDIQLDDDAR VFVQANMDCL PTDWRLVNKF 1570 1580 1590 1600 1610 1620 DSVDGVRTIK YFECPGGIFV SSQGKKFGYV QNGSFKEASV SQIRALLANK VDVLCTVDGV 1630 1640 1650 1660 1670 1680 NFRSCCVAEG EVFGKTLGSV FCDGINVTKV RCSAIYKGKV FFQYSDLSEA DLVAVKDAFG 1690 1700 1710 1720 1730 1740 FDEPQLLKYY TMLGMCKWPV VVCGNYFAFK QSNNNCYINV ACLMLQHLSL KFPKWQWQEA 1750 1760 1770 1780 1790 1800 WNEFRSGKPL RFVSLVLAKG SFKFNEPSDS IDFMRVVLRE ADLSGATCNL EFVCKCGVKQ 1810 1820 1830 1840 1850 1860 EQRKGVDAVM HFGTLDKGDL VRGYNIACTC GSKLVHCTQF NVPFLICSNT PEGRKLPDDV 1870 1880 1890 1900 1910 1920 VAANIFTGGS VGHYTHVKCK PKYQLYDACN VNKVSEAKGN FTDCLYLKNL KQTFSSVLTT 1930 1940 1950 1960 1970 1980 FYLDDVKCVE YKPDLSQYYC ESGKYYTKPI IKAQFRTFEK VDGVYTNFKL VGHSIAEKLN 1990 2000 2010 2020 2030 2040 AKLGFDCNSP FVEYKITEWP TATGDVVLAS DDLYVSRYSS GCITFGKPVV WLGHEEASLK 2050 2060 2070 2080 2090 2100 SLTYFNRPSV VCENKFNVLP VDVSEPTDKG PVPAAVLVTG VPGADASAGA GIAKEQKACA 2110 2120 2130 2140 2150 2160 SASVEDQVVT EVRQEPSVSA ADVKEVKLNG VKKPVKVEGS VVVNDPTSET KVVKSLSIVD 2170 2180 2190 2200 2210 2220 VYDMFLTGCK YVVWTANELS RLVNSPTVRE YVKWGMGKIV TPAKLLLLRD EKQEFVAPKV 2230 2240 2250 2260 2270 2280 VKAKAIACYC AVKWFLLYCF SWIKFNTDNK VIYTTEVASK LTFKLCCLAF KNALQTFNWS 2290 2300 2310 2320 2330 2340 VVSRGFFLVA TVFLLWFNFL YANVILSDFY LPNIGPLPTF VGQIVAWFKT TFGVSTICDF 2350 2360 2370 2380 2390 2400 YQVTDLGYRS SFCNGSMVCE LCFSGFDMLD NYDAINVVQH VVDRRLSFDY ISLFKLVVEL 2410 2420 2430 2440 2450 2460 VIGYSLYTVC FYPLFVLIGM QLLTTWLPEF FMLETMHWSA RLFVFVANML PAFTLLRFYI 2470 2480 2490 2500 2510 2520 VVTAMYKVYC LCRHVMYGCS KPGCLFCYKR NRSVRVKCST VVGGSLRYYD VMANGGTGFC 2530 2540 2550 2560 2570 2580 TKHQWNCLNC NSWKPGNTFI THEAAADLSK ELKRPVNPTD SAYYSVTEVK QVGCSMRLFY 2590 2600 2610 2620 2630 2640 ERDGQRVYDD VNASLFVDMN GLLHSKVKGV PETHVVVVEN EADKAGFLGA AVFYAQSLYR 2650 2660 2670 2680 2690 2700 PMLMVEKKLI TTANTGLSVS RTMFDLYVDS LLNVLDVDRK SLTSFVNAAH NSLKEGVQLE 2710 2720 2730 2740 2750 2760 QVMDTFIGCA RRKCAIDSDV ETKSITKSVM SAVNAGVDFT DESCNNLVPT YVKSDTIVAA 2770 2780 2790 2800 2810 2820 DLGVLIQNNA KHVQANVAKA ANVACIWSVD AFNQLSADLQ HRLRKACSKT GLKIKLTYNK 2830 2840 2850 2860 2870 2880 QEANVPILTT PFSLKGGAVF SRMLQWLFVA NLICFIVLWA LMPTYAVHKS DMQLPLYASF 2890 2900 2910 2920 2930 2940 KVIDNGVLRD VSVTDACFAN KFNQFDQWYE STFGLAYYRN SKACPVVVAV IDQDIGHTLF 2950 2960 2970 2980 2990 3000 NVPTTVLRYG FHVLHFITHA FATDSVQCYT PHMQIPYDNF YASGCVLSSL CTMLAHADGT 3010 3020 3030 3040 3050 3060 PHPYCYTGGV MHNASLYSSL APHVRYNLAS SNGYIRFPEV VSEGIVRVVR TRSMTYCRVG 3070 3080 3090 3100 3110 3120 LCEEAEEGIC FNFNRSWVLN NPYYRAMPGT FCGRNAFDLI HQVLGGLVRP IDFFALTASS 3130 3140 3150 3160 3170 3180 VAGAILAIIV VLAFYYLIKL KRAFGDYTSV VVINVIVWCI NFLMLFVFQV YPTLSCLYAC 3190 3200 3210 3220 3230 3240 FYFYTTLYFP SEISVVMHLQ WLVMYGAIMP LWFCIIYVAV VVSNHALWLF SYCRKIGTEV 3250 3260 3270 3280 3290 3300 RSDGTFEEMA LTTFMITKES YCKLKNSVSD VAFNRYLSLY NKYRYFSGKM DTAAYREAAC 3310 3320 3330 3340 3350 3360 SQLAKAMETF NHNNGNDVLY QPPTASVTTS FLQSGIVKMV SPTSKVEPCI VSVTYGNMTL 3370 3380 3390 3400 3410 3420 NGLWLDDKVY CPRHVICSSA DMTDPDYPNL LCRVTSSDFC VMSGRMSLTV MSYQMQGCQL 3430 3440 3450 3460 3470 3480 VLTVTLQNPN TPKYSFGVVK PGETFTVLAA YNGRPQGAFH VTLRSSHTIK GSFLCGSCGS 3490 3500 3510 3520 3530 3540 VGYVLTGDSV RFVYMHQLEL STGCHTGTDF SGNFYGPYRD AQVVQLPVQD YTQTVNVVAW 3550 3560 3570 3580 3590 3600 LYAAIFNRCN WFVQSDSCSL EEFNVWAMTN GFSSIKADLV LDALASMTGV TVEQVLAAIK 3610 3620 3630 3640 3650 3660 RLHSGFQGKQ ILGSCVLEDE TPSDVYQQLA GVKLQSKRTR VIKGTCCWIL ASTFLFCSII 3670 3680 3690 3700 3710 3720 SAFVKWTMFM YVTTHMLGVT LCALCFVSFA MLLIKHKHLY LTMYIMPVLC TFYTNYLVVY 3730 3740 3750 3760 3770 3780 KQSFRGLAYA WLSHFVPAVD YTYMDEVLYG VVLLVAMVFV TMRSINHDVF SIMFLVGRLV 3790 3800 3810 3820 3830 3840 SLVSMWYFGA NLEEEVLLFL TSLFGTYTWT TMLSLATAKV IAKWLAVNVL YFTDVPQIKL 3850 3860 3870 3880 3890 3900 VLLSYLCIGY VCCCYWGILS LLNSIFRMPL GVYNYKISVQ ELRYMNANGL RPPRNSFEAL 3910 3920 3930 3940 3950 3960 MLNFKLLGIG GVPVIEVSQI QSRLTDVKCA NVVLLNCLQH LHIASNSKLW QYCSTLHNEI 3970 3980 3990 4000 4010 4020 LATSDLSMAF DKLAQLLVVL FANPAAVDSK CLASIEEVSD DYVRDNTVLQ ALQSEFVNMA 4030 4040 4050 4060 4070 4080 SFVEYELAKK NLDEAKASGS ANQQQIKQLE KACNIAKSAY ERDRAVARKL ERMADLALTN 4090 4100 4110 4120 4130 4140 MYKEARINDK KSKVVSALQT MLFSMVRKLD NQALNSILDN AVKGCVPLNA IPSLTSNTLT 4150 4160 4170 4180 4190 4200 IIVPDKQVFD QVVDNVYVTY AGNVWHIQFI QDADGAVKQL NEIDVNSTWP LVIAANRHNE 4210 4220 4230 4240 4250 4260 VSTVVLQNNE LMPQKLRTQV VNSGSDMNCN TPTQCYYNTT GTGKIVYAIL SDCDGLKYTK 4270 4280 4290 4300 4310 4320 IVKEDGNCVV LELDPPCKFS VQDVKGLKIK YLYFVKGCNT LARGWVVGTL SSTVRLQAGT 4330 4340 4350 4360 4370 4380 ATEYASNSAI LSLCAFSVDP KKTYLDYIKQ GGVPVTNCVK MLCDHAGTGM AITIKPEATT 4390 4400 4410 4420 4430 4440 NQDSYGGASV CIYCRSRVEH PDVDGLCKLR GKFVQVPLGI KDPVSYVLTH DVCQVCGFWR 4450 4460 4470 4480 4490 4500 DGSCSCVGTG SQFQSKDTNF LNRIRGTSVN ARLVPCASGL DTDVQLRAFD ICNANRAGIG 4510 4520 4530 4540 4550 4560 LYYKVNCCRF QRVDEDGNKL DKFFVVKRTN LEVYNKEKEC YELTKECGVV AEHEFFTFDV 4570 4580 4590 4600 4610 4620 EGSRVPHIVR KDLSKFTMLD LCYALRHFDR NDCSTLKEIL LTYAECEESY FQKKDWYDFV 4630 4640 4650 4660 4670 4680 ENPDIINVYK KLGPIFNRAL LNTAKFADAL VEAGLVGVLT LDNQDLYGQW YDFGDFVKTV 4690 4700 4710 4720 4730 4740 PGCGVAVADS YYSYMMPMLT MCHALDSELF VNGTYREFDL VQYDFTDFKL ELFTKYFKHW 4750 4760 4770 4780 4790 4800 SMTYHPNTCE CEDDRCIIHC ANFNILFSMV LPKTCFGPLV RQIFVDGVPF VVSIGYHYKE 4810 4820 4830 4840 4850 4860 LGVVMNMDVD THRYRLSLKD LLLYAADPAL HVASASALLD LRTCCFSVAA ITSGVKFQTV 4870 4880 4890 4900 4910 4920 KPGNFNQDFY EFILSKGLLK EGSSVDLKHF FFTQDGNAAI TDYNYYKYNL PTMVDIKQLL 4930 4940 4950 4960 4970 4980 FVLEVVNKYF EIYEGGCIPA TQVIVNNYDK SAGYPFNKFG KARLYYEALS FEEQDEIYAY 4990 5000 5010 5020 5030 5040 TKRNVLPTLT QMNLKYAISA KNRARTVAGV SILSTMTGRM FHQKCLKSIA ATRGVPVVIG 5050 5060 5070 5080 5090 5100 TTKFYGGWDD MLRRLIKDVD SPVLMGWDYP KCDRAMPNIL RIVSSLVLAR KHDSCCSHTD 5110 5120 5130 5140 5150 5160 RFYRLANECA QVLSEIVMCG GCYYVKPGGT SSGDATTAFA NSVFNICQAV SANVCSLMAC 5170 5180 5190 5200 5210 5220 NGHKIEDLSI RELQKRLYSN VYRADHVDPA FVSEYYEFLN KHFSMMILSD DGVVCYNSEF 5230 5240 5250 5260 5270 5280 ASKGYIANIS AFQQVLYYQN NVFMSEAKCW VETDIEKGPH EFCSQHTMLV KMDGDEVYLP 5290 5300 5310 5320 5330 5340 YPDPSRILGA GCFVDDLLKT DSVLLIERFV SLAIDAYPLV YHENPEYQNV FRVYLEYIKK 5350 5360 5370 5380 5390 5400 LYNDLGNQIL DSYSVILSTC DGQKFTDETF YKNMYLRSAV LQSVGACVVC SSQTSLRCGS 5410 5420 5430 5440 5450 5460 CIRKPLLCCK CAYDHVMSTD HKYVLSVSPY VCNSPGCDVN DVTKLYLGGM SYYCEDHKPQ 5470 5480 5490 5500 5510 5520 YSFKLVMNGM VFGLYKQSCT GSPYIEDFNK IASCKWTEVD DYVLANECTE RLKLFAAETQ 5530 5540 5550 5560 5570 5580 KATEEAFKQC YASATIREIV SDRELILSWE IGKVRPPLNK NYVFTGYHFT NNGKTVLGEY 5590 5600 5610 5620 5630 5640 VFDKSELTNG VYYRATTTYK LSVGDVFILT SHAVSSLSAP TLVPQENYTS IRFASVYSVP 5650 5660 5670 5680 5690 5700 ETFQNNVPNY QHIGMKRYCT VQGPPGTGKS HLAIGLAVYY CTARVVYTAA SHAAVDALCE 5710 5720 5730 5740 5750 5760 KAHKFLNIND CTRIVPAKVR VDCYDKFKVN DTTRKYVFTT INALPELVTD IIVVDEVSML 5770 5780 5790 5800 5810 5820 TNYELSVINS RVRAKHYVYI GDPAQLPAPR VLLNKGTLEP RYFNSVTKLM CCLGPDIFLG 5830 5840 5850 5860 5870 5880 TCYRCPKEIV DTVSALVYNN KLKAKNDNSS MCFKVYYKGQ TTHESSSAVN MQQIHLISKF 5890 5900 5910 5920 5930 5940 LKANPSWSNA VFISPYNSQN YVAKRVLGLQ TQTVDSAQGS EYDFVIYSQT AETAHSVNVN 5950 5960 5970 5980 5990 6000 RFNVAITRAK KGILCVMSSM QLFESLNFTT LTLDKINNPR LQCTTNLFKD CSRSYVGYHP 6010 6020 6030 6040 6050 6060 AHAPSFLAVD DKYKVGGDLA VCLNVADSAV TYSRLISLMG FKLDLTLDGY CKLFITRDEA 6070 6080 6090 6100 6110 6120 IKRVRAWVGF DAEGAHAIRD SIGTNFPLQL GFSTGIDFVV EATGMFAERD GYVFKKAAAR 6130 6140 6150 6160 6170 6180 APPGEQFKHL IPLMSRGQKW DVVRIRIVQM LSDHLVDLAD SVVLVTWAAS FELTCLRYFA 6190 6200 6210 6220 6230 6240 KVGREVVCSV CTKRATCFNS RTGYYGCWRH SYSCDYLYNP LIVDIQQWGY TGSLTSNHDP 6250 6260 6270 6280 6290 6300 ICSVHKGAHV ASSDAIMTRC LAVHDCFCKS VNWNLEYPII SNEVSVNTSC RLLQRVMFRA 6310 6320 6330 6340 6350 6360 AMLCNRYDVC YDIGNPKGLA CVKGYDFKFY DASPVVKSVK QFVYKYEAHK DQFLDGLCMF 6370 6380 6390 6400 6410 6420 WNCNVDKYPA NAVVCRFDTR VLNKLNLPGC NGGSLYVNKH AFHTSPFTRA AFENLKPMPF 6430 6440 6450 6460 6470 6480 FYYSDTPCVY MEGMESKQVD YVPLRSATCI TRCNLGGAVC LKHAEEYREY LESYNTATTA 6490 6500 6510 6520 6530 6540 GFTFWVYKTF DFYNLWNTFT RLQSLENVVY NLVNAGHFDG RAGELPCAVI GEKVIAKIQN 6550 6560 6570 6580 6590 6600 EDVVVFKNNT PFPTNVAVEL FAKRSIRPHP ELKLFRNLNI DVCWSHVLWD YAKDSVFCSS 6610 6620 6630 6640 6650 6660 TYKVCKYTDL QCIESLNVLF DGRDNGALEA FKKCRNGVYI NTTKIKSLSM IKGPQRADLN 6670 6680 6690 6700 6710 6720 GVVVEKVGDS DVEFWFAVRK DGDDVIFSRT GSLEPSHYRS PQGNPGGNRV GDLSGNEALA 6730 6740 6750 6760 6770 6780 RGTIFTQSRL LSSFTPRSEM EKDFMDLDDD VFIAKYSLQD YAFEHVVYGS FNQKIIGGLH 6790 6800 6810 6820 6830 6840 LLIGLARRQQ KSNLVIQEFV TYDSSIHSYF ITDENSGSSK SVCTVIDLLL DDFVDIVKSL 6850 6860 6870 6880 6890 6900 NLKCVSKVVN VNVDFKDFQF MLWCNEEKVM TFYPRLQAAA DWKPGYVMPV LYKYLESPLE 6910 6920 6930 6940 6950 6960 RVNLWNYGKP ITLPTGCMMN VAKYTQLCQY LSTTTLAVPA NMRVLHLGAG SDKGVAPGSA 6970 6980 6990 7000 7010 7020 VLRQWLPAGS ILVDNDVNPF VSDSVASYYG NCITLPFDCQ WDLIISDMYD PLTKNIGEYN 7030 7040 7050 7060 7070 7080 VSKDGFFTYL CHLIRDKLAL GGSVAIKITE FSWNAELYSL MGKFAFWTIF CTNVNASSSE 7090 7100 7110 7120 7130 7140 GFLIGINWLN KTRTEIDGKT MHANYLFWRN STMWNGGAYS LFDMSKFPLK AAGTAVVSLK 7150 7160 7170 PDQINDLVLS LIEKGKLLVR DTRKEVFVGD SLVNVK
	Isoform Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [UniParc]. See P0C6V0.		–	–

References

[1]	"The primary structure and expression of the second open reading frame of the polymerase gene of the coronavirus MHV-A59; a highly conserved polymerase is expressed by an efficient ribosomal frameshifting mechanism." Bredenbeek P.J., Pachuk C.J., Noten A.F.H., Charite J., Luytjes W., Weiss S.R., Spaan W.J.M. Nucleic Acids Res. 18:1825-1832(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] (ORF1B).
[2]	"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: NUCLEOTIDE SEQUENCE [GENOMIC RNA] (ORF1A).
[3]	"Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein." Leparc-Goffart I., Hingley S.T., Chua M.M., Jiang X., Lavi E., Weiss S.R. Virology 239:1-10(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate C12 mutant.
[4]	"Molecular cloning of the gene encoding the putative polymerase of mouse hepatitis coronavirus, strain A59." Pachuk C.J., Bredenbeek P.J., Zoltick P.W., Spaan W.J.M., Weiss S.R. Virology 171:141-148(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-597.
[5]	"Mouse hepatitis virus 3C-like protease cleaves a 22-kilodalton protein from the open reading frame 1a polyprotein in virus-infected cells and in vitro." Lu X.T., Sims A.C., Denison M.R. J. Virol. 72:2265-2271(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, CHARACTERIZATION OF NSP8.
[6]	"The putative helicase of the coronavirus mouse hepatitis virus is processed from the replicase gene polyprotein and localizes in complexes that are active in viral RNA synthesis." Denison M.R., Spaan W.J.M., van der Meer Y., Gibson C.A., Sims A.C., Prentice E., Lu X.T. J. Virol. 73:6862-6871(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION OF HELICASE.
[7]	"Further requirements for cleavage by the murine coronavirus 3C-like proteinase: identification of a cleavage site within ORF1b." Pinon J.D., Teng H., Weiss S.R. Virology 263:471-484(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF PHE-3331; LEU-3332; GLN-3333; SER-3334; GLY-3335; ILE-3336; CYS-3478; LEU-5381; GLN-5382 AND SER-5383.
[8]	"Four proteins processed from the replicase gene polyprotein of mouse hepatitis virus colocalize in the cell periphery and adjacent to sites of virion assembly." Bost A.G., Carnahan R.H., Lu X.T., Denison M.R. J. Virol. 74:3379-3387(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, CHARACTERIZATION OF NSP7; NSP9 AND NSP10.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X51939 Genomic RNA. Translation: CAA36202.1. Sequence problems.
X73559 Genomic RNA. No translation available.
AF029248 Genomic RNA. Translation: AAB86818.1. Sequence problems.
AF029248 Genomic RNA. Translation: AAB86820.1. Sequence problems.
M27198 Genomic RNA. Translation: AAA74011.1.

PIR

A32440.
S15760.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GTH	X-ray	2.70	A	6504-6872	[»]
2GTI	X-ray	2.15	A	6504-6872	[»]
3VC8	X-ray	2.00	A/B	3245-3333	[»]
3VCB	X-ray	2.40	A/B	3245-3333	[»]

ProteinModelPortal

P0C6X9.

SMR

P0C6X9. Positions 4049-4199, 4323-4447, 6504-6872.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR027351. (+)RNA_virus_helicase_core_dom.
IPR002589. A1pp.
IPR022570. Coronavirus_NSP1.
IPR009461. Coronavirus_NSP13.
IPR027352. CV_MBD_dom.
IPR009466. NSP11.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR027417. P-loop_NTPase.
IPR002705. Pept_C30/C16_sub.
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.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view]

Pfam

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]

SMART

SM00506. A1pp. 1 hit.
[Graphical view]

SUPFAM

SSF101816. Nsp9. 1 hit.
SSF50494. Pept_Ser_Cys. 1 hit.
SSF144246. SSF144246. 1 hit.
SSF52540. SSF52540. 1 hit.

PROSITE

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]

ProtoNet

Search...

Other

EvolutionaryTrace

P0C6X9.

Entry information

Entry name

R1AB_CVMA5

Accession

Primary (citable) accession number: P0C6X9
Secondary accession number(s): O39225 , O39226, P16342, P19750

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	June 10, 2008
Last modified:	May 29, 2013
This is version 43 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program