P0C6U2 (R1A_CVH22) 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):
   p9
2. Non-structural protein 2
   Short name=nsp2
   Alternative name(s):
   p87
3. Non-structural protein 3
   Short name=nsp3
   EC=3.4.19.12
   EC=3.4.22.-
   Alternative name(s):
   PL1-PRO/PL2-PRO
   PLP1/PLP2
   Papain-like proteinases 1/2
   p195
4. Non-structural protein 4
   Short name=nsp4
   Alternative name(s):
   Peptide HD2
5. 3C-like proteinase
   Short name=3CL-PRO
   Short name=3CLp
   EC=3.4.22.-
   Alternative name(s):
   M-PRO
   nsp5
   p34
6. Non-structural protein 6
   Short name=nsp6
7. Non-structural protein 7
   Short name=nsp7
   Alternative name(s):
   p5
8. Non-structural protein 8
   Short name=nsp8
   Alternative name(s):
   p23
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
    p16
11. Non-structural protein 11
    Short name=nsp11

Gene names

ORF Names:

1a

Organism

Human coronavirus 229E (HCoV-229E) [Reference proteome]

Taxonomic identifier

11137 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Coronaviridae › Coronavirinae › Alphacoronavirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	4085 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 (PLP1) and papain-like proteinase 2 (PLP2) 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. PLP2 also antagonizes innate immune induction of type I interferon by blocking the 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	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 By similarity. 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 By similarity. 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 By similarity. 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 By similarity.
Domain	The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane. Ref.4
Post-translational modification	Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed.
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 innate immune response 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 type I interferon production 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: P0C6U2-1)

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: P0C6X1-1)

Also known as: pp1ab;

The sequence of this isoform can be found in the external entry P0C6X1.
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 – 4085

4085

Replicase polyprotein 1a

PRO_0000338182

Chain

1 – 111

111

Non-structural protein 1

PRO_0000338183

Chain

112 – 897

786

Non-structural protein 2

PRO_0000338184

Chain

898 – 2484

1587

Non-structural protein 3

PRO_0000338185

Chain

2485 – 2965

481

Non-structural protein 4

PRO_0000338186

Chain

2966 – 3267

302

3C-like proteinase

PRO_0000338187

Chain

3268 – 3546

279

Non-structural protein 6

PRO_0000338188

Chain

3547 – 3629

83

Non-structural protein 7

PRO_0000338189

Chain

3630 – 3824

195

Non-structural protein 8

PRO_0000338190

Chain

3825 – 3933

109

Non-structural protein 9

PRO_0000338191

Chain

3934 – 4068

135

Non-structural protein 10

PRO_0000338192

Chain

4069 – 4085

17

Non-structural protein 11 Potential

PRO_0000338193

Regions

Transmembrane

1998 – 2018

21

Helical; Potential

Transmembrane

2068 – 2088

21

Helical; Potential

Transmembrane

2095 – 2115

21

Helical; Potential

Transmembrane

2491 – 2511

21

Helical; Potential

Transmembrane

2731 – 2751

21

Helical; Potential

Transmembrane

2755 – 2775

21

Helical; Potential

Transmembrane

2782 – 2802

21

Helical; Potential

Transmembrane

2809 – 2829

21

Helical; Potential

Transmembrane

2834 – 2854

21

Helical; Potential

Transmembrane

3281 – 3301

21

Helical; Potential

Transmembrane

3304 – 3324

21

Helical; Potential

Transmembrane

3328 – 3348

21

Helical; Potential

Transmembrane

3367 – 3387

21

Helical; Potential

Transmembrane

3401 – 3421

21

Helical; Potential

Transmembrane

3422 – 3442

21

Helical; Potential

Transmembrane

3467 – 3487

21

Helical; Potential

Domain

1016 – 1268

253

Peptidase C16 1

Domain

1269 – 1436

168

Macro

Domain

1663 – 1914

252

Peptidase C16 2

Domain

2966 – 3267

302

Peptidase C30

Zinc finger

1126 – 1157

32

C4-type 1

Zinc finger

1780 – 1815

36

C4-type 2; atypical

Zinc finger

4007 – 4023

17

By similarity

Zinc finger

4049 – 4062

14

By similarity

Region

1925 – 2115

191

HD1

Region

2491 – 2854

364

HD2

Region

3281 – 3487

207

HD3

Sites

Active site

1054

1

For PL1-PRO activity By similarity

Active site

1205

1

For PL1-PRO activity By similarity

Active site

1701

1

For PL2-PRO activity By similarity

Active site

1863

1

For PL2-PRO activity By similarity

Active site

3006

1

For 3CL-PRO activity

Active site

3109

1

For 3CL-PRO activity

Site

111 – 112

2

Cleavage; by PL1-PRO

Site

897 – 898

2

Cleavage; by PL1-PRO

Site

2484 – 2485

2

Cleavage; by PL2-PRO

Site

2965 – 2966

2

Cleavage; by 3CL-PRO

Site

3267 – 3268

2

Cleavage; by 3CL-PRO

Site

3546 – 3547

2

Cleavage; by 3CL-PRO

Site

3629 – 3630

2

Cleavage; by 3CL-PRO

Site

3824 – 3825

2

Cleavage; by 3CL-PRO

Site

3933 – 3934

2

Cleavage; by 3CL-PRO

Site

4068 – 4069

2

Cleavage; by 3CL-PRO

Experimental info

Mutagenesis

1048

1

K → E: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1054

1

C → A, G or S: Complete loss of PL1-PRO activity. Ref.7

Mutagenesis

1099

1

G → A: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1099

1

G → P: No effect. Ref.4

Mutagenesis

1102

1

G → A or S: No effect. Ref.4

Mutagenesis

1126

1

C → D or H: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1128

1

C → A, D or P: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1154

1

C → A, H or D: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1155

1

Missing: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1157

1

C → A, D, H or P: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1163

1

C → A or D: No effect. Ref.4

Mutagenesis

1175

1

V → H or P: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1175

1

V → N or T: No effect. Ref.4

Mutagenesis

1203

1

C → A: Complete loss of PL1-PRO activity. Ref.4

Mutagenesis

1203

1

C → D: No effect. Ref.4

Mutagenesis

1218

1

D → A, E, H, K, N or Q: No effect. Ref.4

Mutagenesis

1702

1

W → L: Complete loss of PL2-PRO activity. Ref.7

Mutagenesis

3006

1

H → G, S, T or Y: Complete loss of 3CL-PRO activity. Ref.3

Mutagenesis

3028

1

H → G or T: No loss of 3CL-PRO activity. Ref.3

Mutagenesis

3029

1

N → A, D, E or Q: Increase of 3CL-PRO activity. Ref.3 Ref.9

Mutagenesis

3029

1

N → G: No loss of 3CL-PRO activity. Ref.3 Ref.9

Mutagenesis

3029

1

N → P: 95% loss of 3CL-PRO activity. Ref.3 Ref.9

Mutagenesis

3074

1

E → H: No loss of 3CL-PRO activity. Ref.3

Mutagenesis

3099

1

T → D: Complete loss of 3CL-PRO activity. Ref.3

Mutagenesis

3109

1

C → P, S or V: Complete loss of 3CL-PRO activity. Ref.3

Mutagenesis

3127

1

H → S: Complete loss of 3CL-PRO activity. Ref.3

Mutagenesis

3136

1

H → A: 67% loss of 3CL-PRO activity. Ref.3

Mutagenesis

3136

1

H → S: 77% loss of 3CL-PRO activity. Ref.3

Mutagenesis

3136

1

H → T: 93% loss of 3CL-PRO activity. Ref.3

Mutagenesis

3267

1

Q → A: No loss of 3CL-PRO activity. Ref.3

Sequence conflict

1982

1

A → Q Ref.1

Sequence conflict

4042

1

F → S Ref.1

Secondary structure

1

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4085

Helix Strand Turn

Details...

Beta strand

1275 – 1278

4

Beta strand

1281 – 1285

5

Helix

1288 – 1294

7

Beta strand

1298 – 1304

7

Helix

1313 – 1321

9

Turn

1322 – 1324

3

Helix

1325 – 1333

9

Beta strand

1345 – 1350

6

Beta strand

1353 – 1359

7

Helix

1367 – 1380

14

Beta strand

1381 – 1383

3

Beta strand

1385 – 1387

3

Helix

1399 – 1409

11

Beta strand

1415 – 1419

5

Helix

1422 – 1433

12

Helix

2976 – 2979

4

Beta strand

2982 – 2987

6

Beta strand

2990 – 2997

8

Beta strand

3000 – 3004

5

Helix

3005 – 3008

4

Helix

3018 – 3024

7

Helix

3027 – 3029

3

Beta strand

3030 – 3034

5

Beta strand

3037 – 3039

3

Beta strand

3041 – 3047

7

Beta strand

3050 – 3057

8

Beta strand

3064 – 3067

4

Beta strand

3075 – 3093

19

Beta strand

3112 – 3117

6

Beta strand

3120 – 3130

11

Beta strand

3136 – 3139

4

Helix

3146 – 3148

3

Beta strand

3151 – 3154

4

Helix

3165 – 3177

13

Helix

3191 – 3199

9

Turn

3200 – 3202

3

Helix

3209 – 3212

4

Helix

3213 – 3219

7

Helix

3223 – 3233

11

Beta strand

3245 – 3247

3

Helix

3254 – 3262

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [UniParc]. Last modified June 10, 2008. Version 1. Checksum: EAB38E3D375F36B5	FASTA	4,085	454,215
	10 20 30 40 50 60 MACNRVTLAV ASDSEISANG CSTIAQAVRR YSEAASNGFR ACRFVSLDLQ DCIVGIADDT 70 80 90 100 110 120 YVMGLHGNQT LFCNIMKFSD RPFMLHGWLV FSNSNYLLEE FDVVFGKRGG GNVTYTDQYL 130 140 150 160 170 180 CGADGKPVMS EDLWQFVDHF GENEEIIING HTYVCAWLTK RKPLDYKRQN NLAIEEIEYV 190 200 210 220 230 240 HGDALHTLRN GSVLEMAKEV KTSSKVVLSD ALDKLYKVFG SPVMTNGSNI LEAFTKPVFI 250 260 270 280 290 300 SALVQCTCGT KSWSVGDWTG FKSSCCNVIS NKLCVVPGNV KPGDAVITTQ QAGAGIKYFC 310 320 330 340 350 360 GMTLKFVANI EGVSVWRVIA LQSVDCFVAS STFVEEEHVN RMDTFCFNVR NSVTDECRLA 370 380 390 400 410 420 MLGAEMTSNV RRQVASGVID ISTGWFDVYD DIFAESKPWF VRKAEDIFGP CWSALASALK 430 440 450 460 470 480 QLKVTTGELV RFVKSICNSA VAVVGGTIQI LASVPEKFLN AFDVFVTAIQ TVFDCAVETC 490 500 510 520 530 540 TIAGKAFDKV FDYVLLDNAL VKLVTTKLKG VRERGLNKVK YATVVVGSTE EVKSSRVERS 550 560 570 580 590 600 TAVLTIANNY SKLFDEGYTV VIGDVAYFVS DGYFRLMASP NSVLTTAVYK PLFAFNVNVM 610 620 630 640 650 660 GTRPEKFPTT VTCENLESAV LFVNDKITEF QLDYSIDVID NEIIVKPNIS LCVPLYVRDY 670 680 690 700 710 720 VDKWDDFCRQ YSNESWFEDD YRAFISVLDI TDAAVKAAES KAFVDTIVPP CPSILKVIDG 730 740 750 760 770 780 GKIWNGVIKN VNSVRDWLKS LKLNLTQQGL LGTCAKRFKR WLGILLEAYN AFLDTVVSTV 790 800 810 820 830 840 KIGGLTFKTY AFDKPYIVIR DIVCKVENKT EAEWIELFPH NDRIKSFSTF ESAYMPIADP 850 860 870 880 890 900 THFDIEEVEL LDAEFVEPGC GGILAVIDEH VFYKKDGVYY PSNGTNILPV AFTKAAGGKV 910 920 930 940 950 960 SFSDDVEVKD IEPVYRVKLC FEFEDEKLVD VCEKAIGKKI KHEGDWDSFC KTIQSALSVV 970 980 990 1000 1010 1020 SCYVNLPTYY IYDEEGGNDL SLPVMISEWP LSVQQAQQEA TLPDIAEDVV DQVEEVNSIF 1030 1040 1050 1060 1070 1080 DIETVDVKHD VSPFEMPFEE LNGLKILKQL DNNCWVNSVM LQIQLTGILD GDYAMQFFKM 1090 1100 1110 1120 1130 1140 GRVAKMIERC YTAEQCIRGA MGDVGLCMYR LLKDLHTGFM VMDYKCSCTS GRLEESGAVL 1150 1160 1170 1180 1190 1200 FCTPTKKAFP YGTCLNCNAP RMCTIRQLQG TIIFVQQKPE PVNPVSFVVK PVCSSIFRGA 1210 1220 1230 1240 1250 1260 VSCGHYQTNI YSQNLCVDGF GVNKIQPWTN DALNTICIKD ADYNAKVEIS VTPIKNTVDT 1270 1280 1290 1300 1310 1320 TPKEEFVVKE KLNAFLVHDN VAFYQGDVDT VVNGVDFDFI VNAANENLAH GGGLAKALDV 1330 1340 1350 1360 1370 1380 YTKGKLQRLS KEHIGLAGKV KVGTGVMVEC DSLRIFNVVG PRKGKHERDL LIKAYNTINN 1390 1400 1410 1420 1430 1440 EQGTPLTPIL SCGIFGIKLE TSLEVLLDVC NTKEVKVFVY TDTEVCKVKD FVSGLVNVQK 1450 1460 1470 1480 1490 1500 VEQPKIEPKP VSVIKVAPKP YRVDGKFSYF TEDLLCVADD KPIVLFTDSM LTLDDRGLAL 1510 1520 1530 1540 1550 1560 DNALSGVLSA AIKDCVDINK AIPSGNLIKF DIGSVVVYMC VVPSEKDKHL DNNVQRCTRK 1570 1580 1590 1600 1610 1620 LNRLMCDIVC TIPADYILPL VLSSLTCNVS FVGELKAAEA KVITIKVTED GVNVHDVTVT 1630 1640 1650 1660 1670 1680 TDKSFEQQVG VIADKDKDLS GAVPSDLNTS ELLTKAIDVD WVEFYGFKDA VTFATVDHSA 1690 1700 1710 1720 1730 1740 FAYESAVVNG IRVLKTSDNN CWVNAVCIAL QYSKPHFISQ GLDAAWNKFV LGDVEIFVAF 1750 1760 1770 1780 1790 1800 VYYVARLMKG DKGDAEDTLT KLSKYLANEA QVQLEHYSSC VECDAKFKNS VASINSAIVC 1810 1820 1830 1840 1850 1860 ASVKRDGVQV GYCVHGIKYY SRVRSVRGRA IIVSVEQLEP CAQSRLLSGV AYTAFSGPVD 1870 1880 1890 1900 1910 1920 KGHYTVYDTA KKSMYDGDRF VKHDLSLLSV TSVVMVGGYV APVNTVKPKP VINQLDEKAQ 1930 1940 1950 1960 1970 1980 KFFDFGDFLI HNFVIFFTWL LSMFTLCKTA VTTGDVKIMA KAPQRTGVVL KRSLKYNLKA 1990 2000 2010 2020 2030 2040 SAAVLKSKWW LLAKFTKLLL LIYTLYSVVL LCVRFGPFNF CSETVNGYAK SNFVKDDYCD 2050 2060 2070 2080 2090 2100 GSLGCKMCLF GYQELSQFSH LDVVWKHITD PLFSNMQPFI VMVLLLIFGD NYLRCFLLYF 2110 2120 2130 2140 2150 2160 VAQMISTVGV FLGYKETNWF LHFIPFDVIC DELLVTVIVI KVISFVRHVL FGCENPDCIA 2170 2180 2190 2200 2210 2220 CSKSARLKRF PVNTIVNGVQ RSFYVNANGG SKFCKKHRFF CVDCDSYGYG STFITPEVSR 2230 2240 2250 2260 2270 2280 ELGNITKTNV QPTGPAYVMI DKVEFENGFY RLYSCETFWR YNFDITESKY SCKEVFKNCN 2290 2300 2310 2320 2330 2340 VLDDFIVFNN NGTNVTQVKN ASVYFSQLLC RPIKLVDSEL LSTLSVDFNG VLHKAYIDVL 2350 2360 2370 2380 2390 2400 RNSFGKDLNA NMSLAECKRA LGLSISDHEF TSAISNAHRC DVLLSDLSFN NFVSSYAKPE 2410 2420 2430 2440 2450 2460 EKLSAYDLAC CMRAGAKVVN ANVLTKDQTP IVWHAKDFNS LSAEGRKYIV KTSKAKGLTF 2470 2480 2490 2500 2510 2520 LLTINENQAV TQIPATSIVA KQGAGDAGHS LTWLWLLCGL VCLIQFYLCF FMPYFMYDIV 2530 2540 2550 2560 2570 2580 SSFEGYDFKY IENGQLKNFE APLKCVRNVF ENFEDWHYAK FGFTPLNKQS CPIVVGVSEI 2590 2600 2610 2620 2630 2640 VNTVAGIPSN VYLVGKTLIF TLQAAFGNAG VCYDIFGVTT PEKCIFTSAC TRLEGLGGNN 2650 2660 2670 2680 2690 2700 VYCYNTALME GSLPYSSIQA NAYYKYDNGN FIKLPEVIAQ GFGFRTVRTI ATKYCRVGEC 2710 2720 2730 2740 2750 2760 VESNAGVCFG FDKWFVNDGR VANGYVCGTG LWNLVFNILS MFSSSFSVAA MSGQILLNCA 2770 2780 2790 2800 2810 2820 LGAFAIFCCF LVTKFRRMFG DLSVGVCTVV VAVLLNNVSY IVTQNLVTMI AYAILYFFAT 2830 2840 2850 2860 2870 2880 RSLRYAWIWC AAYLIAYISF APWWLCAWYF LAMLTGLLPS LLKLKVSTNL FEGDKFVGTF 2890 2900 2910 2920 2930 2940 ESAAAGTFVI DMRSYEKLAN SISPEKLKSY AASYNRYKYY SGNANEADYR CACYAYLAKA 2950 2960 2970 2980 2990 3000 MLDFSRDHND ILYTPPTVSY GSTLQAGLRK MAQPSGFVEK CVVRVCYGNT VLNGLWLGDI 3010 3020 3030 3040 3050 3060 VYCPRHVIAS NTTSAIDYDH EYSIMRLHNF SIISGTAFLG VVGATMHGVT LKIKVSQTNM 3070 3080 3090 3100 3110 3120 HTPRHSFRTL KSGEGFNILA CYDGCAQGVF GVNMRTNWTI RGSFINGACG SPGYNLKNGE 3130 3140 3150 3160 3170 3180 VEFVYMHQIE LGSGSHVGSS FDGVMYGGFE DQPNLQVESA NQMLTVNVVA FLYAAILNGC 3190 3200 3210 3220 3230 3240 TWWLKGEKLF VEHYNEWAQA NGFTAMNGED AFSILAAKTG VCVERLLHAI QVLNNGFGGK 3250 3260 3270 3280 3290 3300 QILGYSSLND EFSINEVVKQ MFGVNLQSGK TTSMFKSISL FAGFFVMFWA ELFVYTTTIW 3310 3320 3330 3340 3350 3360 VNPGFLTPFM ILLVALSLCL TFVVKHKVLF LQVFLLPSII VAAIQNCAWD YHVTKVLAEK 3370 3380 3390 3400 3410 3420 FDYNVSVMQM DIQGFVNIFI CLFVALLHTW RFAKERCTHW CTYLFSLIAV LYTALYSYDY 3430 3440 3450 3460 3470 3480 VSLLVMLLCA ISNEWYIGAI IFRICRFGVA FLPVEYVSYF DGVKTVLLFY MLLGFVSCMY 3490 3500 3510 3520 3530 3540 YGLLYWINRF CKCTLGVYDF CVSPAEFKYM VANGLNAPNG PFDALFLSFK LMGIGGPRTI 3550 3560 3570 3580 3590 3600 KVSTVQSKLT DLKCTNVVLM GILSNMNIAS NSKEWAYCVE MHNKINLCDD PETAQELLLA 3610 3620 3630 3640 3650 3660 LLAFFLSKHS DFGLGDLVDS YFENDSILQS VASSFVGMPS FVAYETARQE YENAVANGSS 3670 3680 3690 3700 3710 3720 PQIIKQLKKA MNVAKAEFDR ESSVQKKINR MAEQAAAAMY KEARAVNRKS KVVSAMHSLL 3730 3740 3750 3760 3770 3780 FGMLRRLDMS SVDTILNMAR NGVVPLSVIP ATSAARLVVV VPDHDSFVKM MVDGFVHYAG 3790 3800 3810 3820 3830 3840 VVWTLQEVKD NDGKNVHLKD VTKENQEILV WPLILTCERV VKLQNNEIMP GKMKVKATKG 3850 3860 3870 3880 3890 3900 EGDGGITSEG NALYNNEGGR AFMYAYVTTK PGMKYVKWEH DSGVVTVELE PPCRFVIDTP 3910 3920 3930 3940 3950 3960 TGPQIKYLYF VKNLNNLRRG AVLGYIGATV RLQAGKQTEF VSNSHLLTHC SFAVDPAAAY 3970 3980 3990 4000 4010 4020 LDAVKQGAKP VGNCVKMLTN GSGSGQAITC TIDSNTTQDT YGGASVCIYC RAHVAHPTMD 4030 4040 4050 4060 4070 4080 GFCQYKGKWV QVPIGTNDPI RFCLENTVCK VCGCWLNHGC TCDRTAIQSF DNSYLNESGA LVPLD
	Isoform Replicase polyprotein 1ab (pp1ab) [UniParc]. See P0C6X1.		–	–

References

[1]	"Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus." Thiel V., Herold J., Schelle B., Siddell S.G. J. Gen. Virol. 82:1273-1281(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Nucleotide sequence of the human coronavirus 229E RNA polymerase locus." Herold J., Raabe T., Schelle-Prinz B., Siddell S.G. Virology 195:680-691(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"Biosynthesis, purification, and characterization of the human coronavirus 229E 3C-like proteinase." Ziebuhr J., Heusipp G., Siddell S.G. J. Virol. 71:3992-3997(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF 3CL-PRO, MUTAGENESIS OF HIS-3006; HIS-3028; ASN-3029; GLU-3074; THR-3099; CYS-3109; HIS-3127; HIS-3136 AND GLN-3267.
[4]	"A human RNA viral cysteine proteinase that depends upon a unique Zn2+-binding finger connecting the two domains of a papain-like fold." Herold J., Siddell S.G., Gorbalenya A.E. J. Biol. Chem. 274:14918-14925(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ZINC-FINGER DOMAIN OF PL1-PRO, MUTAGENESIS OF LYS-1048; GLY-1099; GLY-1102; CYS-1126; CYS-1128; CYS-1154; LEU-1155; CYS-1157; CYS-1163; VAL-1175; CYS-1203 AND ASP-1218.
[5]	Erratum Herold J., Siddell S.G., Gorbalenya A.E. J. Biol. Chem. 274:21490-21490(1999)
[6]	"Processing of the human coronavirus 229E replicase polyproteins by the virus-encoded 3C-like proteinase: identification of proteolytic products and cleavage sites common to pp1a and pp1ab." Ziebuhr J., Siddell S.G. J. Virol. 73:177-185(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[7]	"The autocatalytic release of a putative RNA virus transcription factor from its polyprotein precursor involves two paralogous papain-like proteases that cleave the same peptide bond." Ziebuhr J., Thiel V., Gorbalenya A.E. J. Biol. Chem. 276:33220-33232(2001) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF CYS-1054 AND TRP-1702.
[8]	"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.
[9]	"Mutational analysis of the active centre of coronavirus 3C-like proteases." Hegyi A., Friebe A., Gorbalenya A.E., Ziebuhr J. J. Gen. Virol. 83:581-593(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-3029.
[10]	"Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs." Anand K., Ziebuhr J., Wadhwani P., Mesters J.R., Hilgenfeld R. Science 300:1763-1767(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 2966-3265.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Proteic grace - Issue 77 of December 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF304460 Genomic RNA. Translation: AAG48590.1.
X69721 Genomic RNA. Translation: CAA49377.1.

PIR

S28600.

RefSeq

NP_073550.1. NC_002645.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P9S	X-ray	2.54	A/B	2966-3265	[»]
2ZU2	X-ray	1.80	A/B	2966-3267	[»]
3EWQ	X-ray	2.10	A	1269-1436	[»]
3EWR	X-ray	2.01	A	1269-1436	[»]

ProteinModelPortal

P0C6U2.

SMR

P0C6U2. Positions 2966-3265, 3827-3932, 3940-4064.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

918764.

Family and domain databases

InterPro

IPR002589. A1pp.
IPR014828. NSP7.
IPR014829. NSP8.
IPR014822. NSP9.
IPR011050. Pectin_lyase_fold/virulence.
IPR008740. Peptidase_C30.
IPR013016. Peptidase_C30/C16.
IPR018995. RNA_synth_NSP10_coronavirus.
IPR009003. Trypsin-like_Pept_dom.
IPR014827. Viral_protease.
[Graphical view]

Pfam

PF01661. Macro. 1 hit.
PF09401. NSP10. 1 hit.
PF08716. nsp7. 1 hit.
PF08717. nsp8. 1 hit.
PF08710. nsp9. 1 hit.
PF05409. Peptidase_C30. 1 hit.
PF08715. Viral_protease. 2 hits.
[Graphical view]

SMART

SM00506. A1pp. 1 hit.
[Graphical view]

SUPFAM

SSF101816. Nsp9. 1 hit.
SSF51126. Pectin_lyas_like. 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

Search...

Other

EvolutionaryTrace

P0C6U2.

Entry information

Entry name

R1A_CVH22

Accession

Primary (citable) accession number: P0C6U2
Secondary accession number(s): Q05002

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 10, 2008
Last sequence update:	June 10, 2008
Last modified:	April 3, 2013
This is version 34 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program