P0C6V0 (R1A_CVMA5) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Replicase polyprotein 1a
Short name=pp1a

Alternative name(s):
ORF1a polyprotein

Cleaved into the following 11 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. Non-structural protein 11
    Short name=nsp11

Gene names

ORF Names:

1a

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	4468 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 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. 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.
Catalytic activity	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. Non-structural protein 4: Host membrane; Multi-pass membrane protein Potential. Non-structural protein 6: Host membrane; Multi-pass membrane protein Potential. Non-structural protein 7: Host cytoplasm › host 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. Non-structural protein 8: Host cytoplasm › host 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. Non-structural protein 9: Host cytoplasm › host 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. Non-structural protein 10: Host cytoplasm › host 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.
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 Macro domain. Contains 2 peptidase C16 domains. Contains 1 peptidase C30 domain.

Ontologies

Keywords
Biological process	Activation of host autophagy by virus Host-virus interaction Inhibition of host IFN-mediated response initiation by virus Inhibition of host IRF3 by virus 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 immunoevasion
Cellular component	Host cytoplasm Host membrane Membrane
Coding sequence diversity	Ribosomal frameshifting
Domain	Repeat Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
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 modulation by virus of host protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host IRF3 activity 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 production 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 viral genome replication Inferred from electronic annotation. Source: InterPro viral protein processing Inferred from electronic annotation. Source: InterPro
Cellular_component	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 viral replication complex Inferred from electronic annotation. Source: InterPro
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: InterPro cysteine-type endopeptidase 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 1a (identifier: P0C6V0-1)

Also known as: pp1a; ORF1a polyprotein;

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 conventional translation.

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

Also known as: pp1ab;

The sequence of this isoform can be found in the external entry P0C6X9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 4468

4468

Replicase polyprotein 1a

PRO_0000338278

Chain

1 – 247

247

Non-structural protein 1 Probable

PRO_0000338279

Chain

248 – 832

585

Non-structural protein 2 Probable

PRO_0000338280

Chain

833 – 2837

2005

Non-structural protein 3 Probable

PRO_0000338281

Chain

2838 – 3333

496

Non-structural protein 4

PRO_0000338282

Chain

3334 – 3635

302

3C-like proteinase

PRO_0000338283

Chain

3636 – 3921

286

Non-structural protein 6 Probable

PRO_0000338284

Chain

3922 – 4013

92

Non-structural protein 7

PRO_0000338285

Chain

4014 – 4207

194

Non-structural protein 8

PRO_0000338286

Chain

4208 – 4317

110

Non-structural protein 9

PRO_0000338287

Chain

4318 – 4454

137

Non-structural protein 10

PRO_0000338288

Chain

4455 – 4468

14

Non-structural protein 11 Potential

PRO_0000338289

Regions

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

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

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

Natural variations

Natural variant

1699

1

P → S in strain: Isolate C12 mutant.

Natural variant

2196

1

M → K in strain: Isolate C12 mutant.

Experimental info

Mutagenesis

3331

1

F → A, H or W: No effect. Ref.5

Mutagenesis

3332

1

L → I or S: No processing between peptide HD2 and 3CL-PRO. Ref.5

Mutagenesis

3333

1

Q → A, K or R: No processing between peptide HD2 and 3CL-PRO. Ref.5

Mutagenesis

3334

1

S → A: No effect. Ref.5

Mutagenesis

3334

1

S → C: No processing between peptide HD2 and 3CL-PRO. Ref.5

Mutagenesis

3335

1

G → A: No effect. Ref.5

Mutagenesis

3335

1

G → P: No processing between peptide HD2 and 3CL-PRO. Ref.5

Mutagenesis

3336

1

I → L: No effect. Ref.5

Mutagenesis

3478

1

C → A: Complete loss of 3CL-PRO activity. Ref.5

Sequence conflict

287 – 288

2

WR → CA Ref.3

Sequence conflict

311

1

L → V Ref.3

Sequence conflict

570

1

D → G Ref.3

Sequence conflict

3620

1

E → EL Ref.2

Sequence conflict

3711

1

T → TL Ref.2

Sequence conflict

3968

1

M → V Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

4468

Helix Strand Turn

Details...

Beta strand

840 – 842

3

Beta strand

849 – 853

5

Beta strand

859 – 861

3

Helix

862 – 870

9

Beta strand

874 – 877

4

Helix

882 – 896

15

Helix

904 – 907

4

Helix

909 – 918

10

Beta strand

923 – 930

8

Beta strand

935 – 942

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [UniParc]. Last modified June 10, 2008. Version 1. Checksum: 53FB55E845B646A5	FASTA	4,468	496,341
	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 DGSCSCVGTG SQFQSKDTNF LNGFGVQV
	Isoform Replicase polyprotein 1ab (pp1ab) [UniParc]. See P0C6X9.		–	–

References

[1]	"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].
[2]	"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.
[3]	"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.
[4]	"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.
[5]	"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 AND CYS-3478.
[6]	"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

X73559 Genomic RNA. No translation available.
AF029248 Genomic RNA. Translation: AAB86820.1.
M27198 Genomic RNA. Translation: AAA74011.1.

PIR

A32440.
S15760.

RefSeq

NP_045298.1. NC_001846.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M0A	NMR	-	A	833-946	[»]

ProteinModelPortal

P0C6V0.

SMR

P0C6V0. Positions 4049-4199, 4323-4447.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR002589. A1pp.
IPR022570. Coronavirus_NSP1.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR002705. Pept_C30/C16_sub.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view]

Pfam

PF11963. DUF3477. 2 hits.
PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF01831. Peptidase_C16. 1 hit.
PF05409. Peptidase_C30. 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.

PROSITE

PS51442. M_PRO. 1 hit.
PS51154. MACRO. 1 hit.
PS51124. PEPTIDASE_C16. 2 hits.
[Graphical view]

ProtoNet

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Entry information

Entry name

R1A_CVMA5

Accession

Primary (citable) accession number: P0C6V0
Secondary accession number(s): P16342

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	June 10, 2008
Last modified:	May 1, 2013
This is version 36 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program