Replicase polyprotein 1ab - Equine arteritis virus (strain Bucyrus) (EAV)

Preferred order of sections

Names and origin

Protein names

Recommended name:
Replicase polyprotein 1ab

Alternative name(s):
ORF1ab polyprotein

Cleaved into the following 10 chains:

Nsp1 papain-like cysteine proteinase
Short name=PCP
EC=3.4.22.-
Nsp2 cysteine proteinase
EC=3.4.19.12
EC=3.4.22.-
Alternative name(s):
CP2
Short name=CP
Non-structural protein 3
Short name=Nsp3
3C-like serine proteinase
Short name=3CLSP
EC=3.4.21.-
Alternative name(s):
Nsp4
Non-structural protein 5-6-7
Short name=Nsp5-6-7
Non-structural protein 8
Short name=Nsp8
RNA-directed RNA polymerase
Short name=Pol
Short name=RdRp
EC=2.7.7.48
Alternative name(s):
Nsp9
Helicase
Short name=Hel
EC=3.6.4.12
EC=3.6.4.13
Alternative name(s):
Nsp10
Non-structural protein 11
Short name=Nsp11
Non-structural protein 12
Short name=Nsp12

Gene names

Name:	rep
ORF Names:	1a-1b

Organism

Equine arteritis virus (strain Bucyrus) (EAV) [Reference proteome]

Taxonomic identifier

299386 [NCBI]

Taxonomic lineage

Viruses › ssRNA positive-strand viruses, no DNA stage › Nidovirales › Arteriviridae › Arterivirus ›

Virus host

Equidae (horses) [TaxID: 9788]

Protein attributes

Sequence length	3175 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 1ab 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. Ref.15 Nsp1 is essential for viral subgenomic mRNA synthesis. Ref.15 Nsp2 cysteine proteinase which cleaves the nsp2/nsp3 site in the polyprotein. Also displays deubiquitinating and deISGylase activities. The deubiquitinating activity cleaves both ubiquitinated and ISGylated products and may therefore regulate ubiquitin and ISG15 dependent host innate immunity. Ref.15 The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein. Ref.15 The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Ref.15
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). ATP + H₂O = ADP + phosphate. 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	Nsp1 interacts with cellular transcription cofactor SND1/p100. Ref.14
Subcellular location	Nsp1 papain-like cysteine proteinase: Host nucleus. Host cytoplasm Ref.9 Ref.13. Nsp2 cysteine proteinase: Host membrane; Multi-pass membrane protein Potential Ref.9 Ref.13. Non-structural protein 3: Host membrane; Multi-pass membrane protein Potential Ref.9 Ref.13. Non-structural protein 5-6-7: Host membrane; Multi-pass membrane protein Potential Ref.9 Ref.13. 3C-like serine proteinase: Host cytoplasm Potential Ref.9 Ref.13. RNA-directed RNA polymerase: Host cytoplasm › host perinuclear region Potential Ref.9 Ref.13. Helicase: Host cytoplasm › host perinuclear region Potential Ref.9 Ref.13.
Domain	The hydrophobic domains (HD) could mediate the membrane association of the replication complex and thereby alter the architecture of the host cell membrane. The OTU-like region is responsible for the deubiquitinating and deISGylation activities of Nsp2 Probable.
Post-translational modification	Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. There are two alternative pathways for processing. Either nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and nsp6-7 are processed, which represents the minor pathway. The major pathway occurs when nsp2 acts as cofactor for nsp4. Ref.4 Ref.6 Ref.8 Ref.10
Miscellaneous	Nsp1 contains an inactivated papain-like cysteine proteinase domain due to a Lys instead of a Cys in position 73.
Sequence similarities	Belongs to the arteriviridae polyprotein family. Contains 1 (+)RNA virus helicase ATP-binding domain. Contains 1 (+)RNA virus helicase C-terminal domain. Contains 1 AV MBD (arterivirus metal-binding) domain. Contains 1 peptidase C31 domain. Contains 1 peptidase C32 domain. Contains 1 peptidase C33 domain. Contains 1 peptidase S32 domain. Contains 1 RdRp catalytic domain.

Ontologies

Keywords
Biological process	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 Viral RNA replication Viral immunoevasion
Cellular component	Host cytoplasm Host membrane Host nucleus Membrane
Coding sequence diversity	Ribosomal frameshifting
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Helicase Hydrolase Nucleotidyltransferase Protease RNA-directed RNA polymerase Serine protease Thiol protease Transferase
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	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 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 membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus 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: InterPro RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro helicase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type exopeptidase activity 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: P19811-1) 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: P19811-2) Also known as: pp1a; ORF1a polyprotein; The sequence of this isoform differs from the canonical sequence as follows: 1728-3175: Missing.
Note: Produced by conventional translation.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 3175

3175

Replicase polyprotein 1ab

PRO_0000036619

Chain

1 – 260

260

Nsp1 papain-like cysteine proteinase

PRO_0000036621

Chain

261 – 831

571

Nsp2 cysteine proteinase

PRO_0000036622

Chain

832 – 1064

233

Non-structural protein 3

PRO_0000036623

Chain

1065 – 1268

204

3C-like serine proteinase

PRO_0000036624

Chain

1269 – 1677

409

Non-structural protein 5-6-7

PRO_0000036625

Chain

1678 – 2370

693

RNA-directed RNA polymerase

PRO_0000036626

Chain

1678 – 1727

50

Non-structural protein 8

PRO_0000036627

Chain

2371 – 2837

467

Helicase By similarity

PRO_0000036628

Chain

2838 – 3056

219

Non-structural protein 11

PRO_0000036629

Chain

3057 – 3175

119

Non-structural protein 12

PRO_0000036630

Regions

Transmembrane

530 – 550

21

Helical; Potential

Transmembrane

551 – 571

21

Helical; Potential

Transmembrane

625 – 645

21

Helical; Potential

Transmembrane

829 – 849

21

Helical; Potential

Transmembrane

903 – 923

21

Helical; Potential

Transmembrane

935 – 955

21

Helical; Potential

Transmembrane

977 – 997

21

Helical; Potential

Transmembrane

1291 – 1311

21

Helical; Potential

Transmembrane

1333 – 1353

21

Helical; Potential

Transmembrane

1355 – 1375

21

Helical; Potential

Transmembrane

1385 – 1405

21

Helical; Potential

Domain

66 – 156

91

Peptidase C31

Domain

157 – 260

104

Peptidase C32

Domain

261 – 360

100

Peptidase C33

Domain

1065 – 1268

204

Peptidase S32

Domain

2116 – 2251

136

RdRp catalytic

Domain

2371 – 2438

68

AV MBD

Domain

2496 – 2661

166

(+)RNA virus helicase ATP-binding

Domain

2662 – 2793

132

(+)RNA virus helicase C-terminal

Zinc finger

25 – 44

20

C4-type; atypical

Nucleotide binding

2528 – 2535

8

ATP By similarity

Region

261 – 339

79

OTU-like

Region

530 – 645

116

HD1

Region

829 – 997

169

HD2

Region

1291 – 1405

115

HD3

Compositional bias

389 – 440

52

Pro-rich

Sites

Active site

164

1

For Nsp1 papain-like cysteine proteinase activity

Active site

230

1

For Nsp1 papain-like cysteine proteinase activity

Active site

270

1

For Nsp2 cysteine proteinase activity

Active site

332

1

For Nsp2 cysteine proteinase activity

Active site

1103

1

Charge relay system; for 3C-like serine proteinase activity By similarity

Active site

1129

1

Charge relay system; for 3C-like serine proteinase activity By similarity

Active site

1184

1

Charge relay system; for 3C-like serine proteinase activity By similarity

Site

260 – 261

2

Cleavage; by PCP

Site

831 – 832

2

Cleavage; by Nsp2 cysteine proteinase

Site

1064 – 1065

2

Cleavage; by 3CLSP

Site

1268 – 1269

2

Cleavage; by 3CLSP; in major pathway

Site

1430 – 1431

2

Cleavage; by 3CLSP; in minor pathway

Site

1452 – 1453

2

Cleavage; by 3CLSP; in minor pathway

Site

1677 – 1678

2

Cleavage; by 3CLSP

Site

2370 – 2371

2

Cleavage; by 3CLSP

Site

2429

1

Involved in mRNA transcription process

Site

2837 – 2838

2

Cleavage; by 3CLSP

Site

3056 – 3057

2

Cleavage; by 3CLSP

Amino acid modifications

Glycosylation

1501

1

N-linked (GlcNAc...); by host Probable

Natural variations

Alternative sequence

1728 – 3175

1448

Missing in isoform Replicase polyprotein 1a.

VSP_032887

Experimental info

Mutagenesis

25

1

C → A: Complete loss of transcription. Ref.12

Mutagenesis

44

1

C → A: Complete loss of transcription. Ref.12

Mutagenesis

164

1

C → G or S: Complete loss of PCP proteinase activity. Ref.4 Ref.6

Mutagenesis

219

1

H → A, G or V: No effect. Ref.4

Mutagenesis

230

1

H → A, G or V: Complete loss of PCP proteinase activity. Ref.4

Mutagenesis

260

1

G → V: Complete loss of nsp1-nsp2 cleavage. Ref.4

Mutagenesis

270

1

C → A, H, R or S: Complete loss of CP2 activity. Ref.5

Mutagenesis

271

1

G → W: Complete loss of CP2 activity. Ref.5

Mutagenesis

291

1

D → E or N: No effect. Ref.5

Mutagenesis

295

1

D → E or N: No effect. Ref.5

Mutagenesis

296

1

D → E or N: No effect. Ref.5

Mutagenesis

297

1

E → D or Q: No effect. Ref.5

Mutagenesis

319

1

C → A, H or P: Complete loss of CP2 activity. Ref.5

Mutagenesis

332

1

H → C, I, N or Y: Complete loss of CP2 activity. Ref.5

Mutagenesis

344

1

C → A: No effect. Ref.5

Mutagenesis

344

1

C → H: Almost complete loss of CP2 activity. Ref.5

Mutagenesis

349

1

C → A, H or S: Complete loss of CP2 activity. Ref.5

Mutagenesis

354

1

C → A, H or P: Complete loss of CP2 activity. Ref.5

Mutagenesis

356

1

C → A: Complete loss of CP2 activity. Ref.5

Mutagenesis

356

1

C → H: No effect. Ref.5

Mutagenesis

831

1

G → P: Complete loss of nsp2-nsp3 cleavage. Ref.6

Mutagenesis

1064

1

E → P: Complete loss of nsp3-nsp4 cleavage. Ref.6

Mutagenesis

1103

1

H → G or R: Complete loss of nsp3-nsp4, nsp4-nsp5 and nsp5-nsp6 cleavages. Ref.6

Mutagenesis

1117

1

D → N or T: No effect. Ref.6

Mutagenesis

1129

1

D → E: Complete loss of nsp3-nsp4 and nsp5-nsp6 cleavages. Ref.6

Mutagenesis

1129

1

D → K or V: Complete loss of nsp3-nsp4, nsp4-nsp5 and nsp5-nsp6 cleavages. Ref.6

Mutagenesis

1179

1

T → G or S: Partial loss of nsp4-nsp5 cleavage. Ref.6

Mutagenesis

1179

1

T → N: Increased nsp5-nsp6 cleavage. Ref.6

Mutagenesis

1184

1

S → C, F, I or T: Complete loss of nsp3-nsp4, nsp4-nsp5 and nsp5-nsp6 cleavages. Ref.6

Mutagenesis

1198

1

H → L, R or Y: Complete loss of nsp4-nsp5 and nsp5-nsp6 cleavages. Ref.6

Mutagenesis

1268

1

E → P: Complete loss of nsp3-nsp4 and nsp4-nsp5 cleavages. Ref.6 Ref.8

Mutagenesis

1430

1

E → P: No effect. Ref.6

Mutagenesis

1677

1

E → P: Complete loss of nsp5-nsp6 cleavage. Ref.6

Mutagenesis

2351

1

D → P: No effect. Ref.10

Mutagenesis

2370

1

E → P: Complete loss of nsp9-nsp10 cleavage. Ref.10

Mutagenesis

2429

1

S → P: RNA can replicate efficiently but does not produce the subgenomic mRNAs required for structural protein expression. Ref.7

Mutagenesis

2800

1

E → P: No effect. Ref.10

Mutagenesis

2819

1

D → P: No effect. Ref.10

Mutagenesis

2835

1

E → D, P or Q: Almost complete loss of nsp9-nsp10 cleavage. Ref.10

Mutagenesis

2837

1

Q → D or N: No effect. Ref.10

Mutagenesis

2837

1

Q → E: Increased nsp9-nsp10 cleavage. Ref.10

Mutagenesis

2837

1

Q → P: Almost complete loss of nsp9-nsp10 cleavage. Ref.10

Mutagenesis

3056

1

E → P: Complete loss of nsp10-nsp11 cleavage. Ref.10

Secondary structure

1

.

3175

Helix Strand Turn

Details...

Sequences

Sequence		Length	Mass (Da)
Isoform Replicase polyprotein 1ab (pp1ab) [UniParc]. Last modified April 13, 2004. Version 3. Checksum: CB536C1F5091045C Show »	FASTA	3,175	345,384
10 20 30 40 50 60 MATFSATGFG GSFVRDWSLD LPDACEHGAG LCCEVDGSTL CAECFRGCEG MEQCPGLFMG 70 80 90 100 110 120 LLKLASPVPV GHKFLIGWYR AAKVTGRYNF LELLQHPAFA QLRVVDARLA IEEASVFIST 130 140 150 160 170 180 DHASAKRFPG ARFALTPVYA NAWVVSPAAN SLIVTTDQEQ DGFCWLKLLP PDRREAGLRL 190 200 210 220 230 240 YYNHYREQRT GWLSKTGLRL WLGDLGLGIN ASSGGLKFHI MRGSPQRAWH ITTRSCKLKS 250 260 270 280 290 300 YYVCDISEAD WSCLPAGNYG GYNPPGDGAC GYRCLAFMNG ATVVSAGCSS DLWCDDELAY 310 320 330 340 350 360 RVFQLSPTFT VTIPGGRVCP NAKYAMICDK QHWRVKRAKG VGLCLDESCF RGICNCQRMS 370 380 390 400 410 420 GPPPAPVSAA VLDHILEAAT FGNVRVVTPE GQPRPVPAPR VRPSANSSGD VKDPAPVPPV 430 440 450 460 470 480 PKPRTKLATP NPTQAPIPAP RTRLQGASTQ EPLASAGVAS DSAPKWRVAK TVYSSAERFR 490 500 510 520 530 540 TELVQRARSV GDVLVQALPL KTPAVQRYTM TLKMMRSRFS WHCDVWYPLA VIACLLPIWP 550 560 570 580 590 600 SLALLLSFAI GLIPSVGNNV VLTALLVSSA NYVASMDHQC EGAACLALLE EEHYYRAVRW 610 620 630 640 650 660 RPITGALSLV LNLLGQVGYV ARSTFDAAYV PCTVFDLCSF AILYLCRNRC WRCFGRCVRV 670 680 690 700 710 720 GPATHVLGST GQRVSKLALI DLCDHFSKPT IDVVGMATGW SGCYTGTAAM ERQCASTVDP 730 740 750 760 770 780 HSFDQKKAGA TVYLTPPVNS GSALQCLNVM WKRPIGSTVL GEQTGAVVTA VKSISFSPPC 790 800 810 820 830 840 CVSTTLPTRP GVTVVDHALY NRLTASGVDP ALLRVGQGDF LKLNPGFRLI GGWIYGICYF 850 860 870 880 890 900 VLVVVSTFTC LPIKCGIGTR DPFCRRVFSV PVTKTQEHCH AGMCASAEGI SLDSLGLTQL 910 920 930 940 950 960 QSYWIAAVTS GLVILLVCHR LAISALDLLT LASPLVLLVF PWASVGLLLA CSLAGAAVKI 970 980 990 1000 1010 1020 QLLATLFVNL FFPQATLVTM GYWACVAALA VYSLMGLRVK VNVPMCVTPA HFLLLARSAG 1030 1040 1050 1060 1070 1080 QSREQMLRVS AAAPTNSLLG VARDCYVTGT TRLYIPKEGG MVFEGLFRSP KARGNVGFVA 1090 1100 1110 1120 1130 1140 GSSYGTGSVW TRNNEVVVLT ASHVVGRANM ATLKIGDAML TLTFKKNGDF AEAVTTQSEL 1150 1160 1170 1180 1190 1200 PGNWPQLHFA QPTTGPASWC TATGDEEGLL SGEVCLAWTT SGDSGSAVVQ GDAVVGVHTG 1210 1220 1230 1240 1250 1260 SNTSGVAYVT TPSGKLLGAD TVTLSSLSKH FTGPLTSIPK DIPDNIIADV DAVPRSLAML 1270 1280 1290 1300 1310 1320 IDGLSNRESS LSGPQLLLIA CFMWSYLNQP AYLPYVLGFF AANFFLPKSV GRPVVTGLLW 1330 1340 1350 1360 1370 1380 LCCLFTPLSM RLCLFHLVCA TVTGNVISLW FYITAAGTSY LSEMWFGGYP TMLFVPRFLV 1390 1400 1410 1420 1430 1440 YQFPGWAIGT VLAVCSITML AAALGHTLLL DVFSASGRFD RTFMMKYFLE GGVKESVTAS 1450 1460 1470 1480 1490 1500 VTRAYGKPIT QESLTATLAA LTDDDFQFLS DVLDCRAVRS AMNLRAALTS FQVAQYRNIL 1510 1520 1530 1540 1550 1560 NASLQVDRDA ARSRRLMAKL ADFAVEQEVT AGDRVVVIDG LDRMAHFKDD LVLVPLTTKV 1570 1580 1590 1600 1610 1620 VGGSRCTICD VVKEEANDTP VKPMPSRRRR KGLPKGAQLE WDRHQEEKRN AGDDDFAVSN 1630 1640 1650 1660 1670 1680 DYVKRVPKYW DPSDTRGTTV KIAGTTYQKV VDYSGNVHYV EHQEDLLDYV LGKGSYEGLD 1690 1700 1710 1720 1730 1740 QDKVLDLTNM LKVDPTELSS KDKAKARQLA HLLLDLANPV EAVNQLNLRA PHIFPGDVGR 1750 1760 1770 1780 1790 1800 RTFADSKDKG FVALHSRTMF LAARDFLFNI KFVCDEEFTK TPKDTLLGYV RACPGYWFIF 1810 1820 1830 1840 1850 1860 RRTHRSLIDA YWDSMECVYA LPTISDFDVS PGDVAVTGER WDFESPGGGR AKRLTADLVH 1870 1880 1890 1900 1910 1920 AFQGFHGASY SYDDKVAAAV SGDPYRSDGV LYNTRWGNIP YSVPTNALEA TACYRAGCEA 1930 1940 1950 1960 1970 1980 VTDGTNVIAT IGPFPEQQPI PDIPKSVLDN CADISCDAFI APAAETALCG DLEKYNLSTQ 1990 2000 2010 2020 2030 2040 GFVLPSVFSM VRAYLKEEIG DAPPLYLPST VPSKNSQAGI NGAEFPTKSL QSYCLIDDMV 2050 2060 2070 2080 2090 2100 SQSMKSNLQT ATMATCKRQY CSKYKIRSIL GTNNYIGLGL RACLSGVTAA FQKAGKDGSP 2110 2120 2130 2140 2150 2160 IYLGKSKFDP IPAPDKYCLE TDLESCDRST PALVRWFATN LIFELAGQPE LVHSYVLNCC 2170 2180 2190 2200 2210 2220 HDLVVAGSVA FTKRGGLSSG DPITSISNTI YSLVLYTQHM LLCGLEGYFP EIAEKYLDGS 2230 2240 2250 2260 2270 2280 LELRDMFKYV RVYIYSDDVV LTTPNQHYAA SFDRWVPHLQ ALLGFKVDPK KTVNTSSPSF 2290 2300 2310 2320 2330 2340 LGCRFKQVDG KCYLASLQDR VTRSLLYHIG AKNPSEYYEA AVSIFKDSII CCDEDWWTDL 2350 2360 2370 2380 2390 2400 HRRISGAART DGVEFPTIEM LTSFRTKQYE SAVCTVCGAA PVAKSACGGW FCGNCVPYHA 2410 2420 2430 2440 2450 2460 GHCHTTSLFA NCGHDIMYRS TYCTMCEGSP KQMVPKVPHP ILDHLLCHID YGSKEELTLV 2470 2480 2490 2500 2510 2520 VADGRTTSPP GRYKVGHKVV AVVADVGGNI VFGCGPGSHI AVPLQDTLKG VVVNKALKNA 2530 2540 2550 2560 2570 2580 AASEYVEGPP GSGKTFHLVK DVLAVVGSAT LVVPTHASML DCINKLKQAG ADPYFVVPKY 2590 2600 2610 2620 2630 2640 TVLDFPRPGS GNITVRLPQV GTSEGETFVD EVAYFSPVDL ARILTQGRVK GYGDLNQLGC 2650 2660 2670 2680 2690 2700 VGPASVPRNL WLRHFVSLEP LRVCHRFGAA VCDLIKGIYP YYEPAPHTTK VVFVPNPDFE 2710 2720 2730 2740 2750 2760 KGVVITAYHK DRGLGHRTID SIQGCTFPVV TLRLPTPQSL TRPRAVVAVT RASQELYIYD 2770 2780 2790 2800 2810 2820 PFDQLSGLLK FTKEAEAQDL IHGPPTACHL GQEIDLWSNE GLEYYKEVNL LYTHVPIKDG 2830 2840 2850 2860 2870 2880 VIHSYPNCGP ACGWEKQSNK ISCLPRVAQN LGYHYSPDLP GFCPIPKELA EHWPVVSNDR 2890 2900 2910 2920 2930 2940 YPNCLQITLQ QVCELSKPCS AGYMVGQSVF VQTPGVTSYW LTEWVDGKAR ALPDSLFSSG 2950 2960 2970 2980 2990 3000 RFETNSRAFL DEAEEKFAAA HPHACLGEIN KSTVGGSHFI FSQYLPPLLP ADAVALVGAS 3010 3020 3030 3040 3050 3060 LAGKAAKAAC SVVDVYAPSF EPYLHPETLS RVYKIMIDFK PCRLMVWRNA TFYVQEGVDA 3070 3080 3090 3100 3110 3120 VTSALAAVSK LIKVPANEPV SFHVASGYRT NALVAPQAKI SIGAYAAEWA LSTEPPPAGY 3130 3140 3150 3160 3170 AIVRRYIVKR LLSSTEVFLC RRGVVSSTSV QTICALEGCK PLFNFLQIGS VIGPV « Hide
Isoform Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [UniParc]. Checksum: FB0DB046FA0C74F6 Show »	FASTA	1,727	186,992
10 20 30 40 50 60 MATFSATGFG GSFVRDWSLD LPDACEHGAG LCCEVDGSTL CAECFRGCEG MEQCPGLFMG 70 80 90 100 110 120 LLKLASPVPV GHKFLIGWYR AAKVTGRYNF LELLQHPAFA QLRVVDARLA IEEASVFIST 130 140 150 160 170 180 DHASAKRFPG ARFALTPVYA NAWVVSPAAN SLIVTTDQEQ DGFCWLKLLP PDRREAGLRL 190 200 210 220 230 240 YYNHYREQRT GWLSKTGLRL WLGDLGLGIN ASSGGLKFHI MRGSPQRAWH ITTRSCKLKS 250 260 270 280 290 300 YYVCDISEAD WSCLPAGNYG GYNPPGDGAC GYRCLAFMNG ATVVSAGCSS DLWCDDELAY 310 320 330 340 350 360 RVFQLSPTFT VTIPGGRVCP NAKYAMICDK QHWRVKRAKG VGLCLDESCF RGICNCQRMS 370 380 390 400 410 420 GPPPAPVSAA VLDHILEAAT FGNVRVVTPE GQPRPVPAPR VRPSANSSGD VKDPAPVPPV 430 440 450 460 470 480 PKPRTKLATP NPTQAPIPAP RTRLQGASTQ EPLASAGVAS DSAPKWRVAK TVYSSAERFR 490 500 510 520 530 540 TELVQRARSV GDVLVQALPL KTPAVQRYTM TLKMMRSRFS WHCDVWYPLA VIACLLPIWP 550 560 570 580 590 600 SLALLLSFAI GLIPSVGNNV VLTALLVSSA NYVASMDHQC EGAACLALLE EEHYYRAVRW 610 620 630 640 650 660 RPITGALSLV LNLLGQVGYV ARSTFDAAYV PCTVFDLCSF AILYLCRNRC WRCFGRCVRV 670 680 690 700 710 720 GPATHVLGST GQRVSKLALI DLCDHFSKPT IDVVGMATGW SGCYTGTAAM ERQCASTVDP 730 740 750 760 770 780 HSFDQKKAGA TVYLTPPVNS GSALQCLNVM WKRPIGSTVL GEQTGAVVTA VKSISFSPPC 790 800 810 820 830 840 CVSTTLPTRP GVTVVDHALY NRLTASGVDP ALLRVGQGDF LKLNPGFRLI GGWIYGICYF 850 860 870 880 890 900 VLVVVSTFTC LPIKCGIGTR DPFCRRVFSV PVTKTQEHCH AGMCASAEGI SLDSLGLTQL 910 920 930 940 950 960 QSYWIAAVTS GLVILLVCHR LAISALDLLT LASPLVLLVF PWASVGLLLA CSLAGAAVKI 970 980 990 1000 1010 1020 QLLATLFVNL FFPQATLVTM GYWACVAALA VYSLMGLRVK VNVPMCVTPA HFLLLARSAG 1030 1040 1050 1060 1070 1080 QSREQMLRVS AAAPTNSLLG VARDCYVTGT TRLYIPKEGG MVFEGLFRSP KARGNVGFVA 1090 1100 1110 1120 1130 1140 GSSYGTGSVW TRNNEVVVLT ASHVVGRANM ATLKIGDAML TLTFKKNGDF AEAVTTQSEL 1150 1160 1170 1180 1190 1200 PGNWPQLHFA QPTTGPASWC TATGDEEGLL SGEVCLAWTT SGDSGSAVVQ GDAVVGVHTG 1210 1220 1230 1240 1250 1260 SNTSGVAYVT TPSGKLLGAD TVTLSSLSKH FTGPLTSIPK DIPDNIIADV DAVPRSLAML 1270 1280 1290 1300 1310 1320 IDGLSNRESS LSGPQLLLIA CFMWSYLNQP AYLPYVLGFF AANFFLPKSV GRPVVTGLLW 1330 1340 1350 1360 1370 1380 LCCLFTPLSM RLCLFHLVCA TVTGNVISLW FYITAAGTSY LSEMWFGGYP TMLFVPRFLV 1390 1400 1410 1420 1430 1440 YQFPGWAIGT VLAVCSITML AAALGHTLLL DVFSASGRFD RTFMMKYFLE GGVKESVTAS 1450 1460 1470 1480 1490 1500 VTRAYGKPIT QESLTATLAA LTDDDFQFLS DVLDCRAVRS AMNLRAALTS FQVAQYRNIL 1510 1520 1530 1540 1550 1560 NASLQVDRDA ARSRRLMAKL ADFAVEQEVT AGDRVVVIDG LDRMAHFKDD LVLVPLTTKV 1570 1580 1590 1600 1610 1620 VGGSRCTICD VVKEEANDTP VKPMPSRRRR KGLPKGAQLE WDRHQEEKRN AGDDDFAVSN 1630 1640 1650 1660 1670 1680 DYVKRVPKYW DPSDTRGTTV KIAGTTYQKV VDYSGNVHYV EHQEDLLDYV LGKGSYEGLD 1690 1700 1710 1720 QDKVLDLTNM LKVDPTELSS KDKAKARQLA HLLLDLANPV EAVNQLN « Hide

References

[1]	"Equine arteritis virus is not a togavirus but belongs to the coronaviruslike superfamily." den Boon J.A., Snijder E.J., Chirnside E.D., de Vries A.A.F., Horzinek M.C., Spaan W.J.M. J. Virol. 65:2910-2920(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	Snijder E.J. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"All subgenomic mRNAs of equine arteritis virus contain a common leader sequence." de Vries A.A.F., Chirnside E.D., Bredenbeek P.J., Gravestein L.A., Horzinek M.C., Spaan W.J.M. Nucleic Acids Res. 18:3241-3247(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-17.
[4]	"The 5' end of the equine arteritis virus replicase gene encodes a papainlike cysteine protease." Snijder E.J., Wassenaar A.L.M., Spaan W.J.M. J. Virol. 66:7040-7048(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, CHARACTERIZATION OF PCP, MUTAGENESIS OF CYS-164; HIS-219; HIS-230 AND GLY-260.
[5]	"The arterivirus Nsp2 protease. An unusual cysteine protease with primary structure similarities to both papain-like and chymotrypsin-like proteases." Snijder E.J., Wassenaar A.L.M., Spaan W.J.M., Gorbalenya A.E. J. Biol. Chem. 270:16671-16676(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF NSP2, MUTAGENESIS OF CYS-270; GLY-271; ASP-291; ASP-295; ASP-296; GLU-297; CYS-319; HIS-332; CYS-344; CYS-349; CYS-354 AND CYS-356.
[6]	"The arterivirus nsp4 protease is the prototype of a novel group of chymotrypsin-like enzymes, the 3C-like serine proteases." Snijder E.J., Wassenaar A.L.M., van Dinten L.C., Spaan W.J.M., Gorbalenya A.E. J. Biol. Chem. 271:4864-4871(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, CHARACTERIZATION OF 3CLSP, MUTAGENESIS OF CYS-164; GLY-831; GLU-1064; HIS-1103; ASP-1117; ASP-1129; THR-1179; SER-1184; HIS-1198; GLU-1268; GLU-1430 AND GLU-1677.
[7]	"An infectious arterivirus cDNA clone: identification of a replicase point mutation that abolishes discontinuous mRNA transcription." van Dinten L.C., den Boon J.A., Wassenaar A.L.M., Spaan W.J.M., Snijder E.J. Proc. Natl. Acad. Sci. U.S.A. 94:991-996(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF SER-2429.
[8]	"Alternative proteolytic processing of the arterivirus replicase ORF1a polyprotein: evidence that NSP2 acts as a cofactor for the NSP4 serine protease." Wassenaar A.L.M., Spaan W.J.M., Gorbalenya A.E., Snijder E.J. J. Virol. 71:9313-9322(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN 1A, MUTAGENESIS OF GLU-1268.
[9]	"ORF1a-encoded replicase subunits are involved in the membrane association of the arterivirus replication complex." van der Meer Y., van Tol H., Locker J.K., Snijder E.J. J. Virol. 72:6689-6698(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and is essential for virus replication." van Dinten L.C., Rensen S., Gorbalenya A.E., Snijder E.J. J. Virol. 73:2027-2037(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN 1B, MUTAGENESIS OF ASP-2351; GLU-2370; GLU-2800; ASP-2819; GLU-2835; GLN-2837 AND GLU-3056.
[11]	"Biochemical characterization of the equine arteritis virus helicase suggests a close functional relationship between arterivirus and coronavirus helicases." Seybert A., van Dinten L.C., Snijder E.J., Ziebuhr J. J. Virol. 74:9586-9593(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF HELICASE.
[12]	"A zinc finger-containing papain-like protease couples subgenomic mRNA synthesis to genome translation in a positive-stranded RNA virus." Tijms M.A., van Dinten L.C., Gorbalenya A.E., Snijder E.J. Proc. Natl. Acad. Sci. U.S.A. 98:1889-1894(2001) [PubMed] [Europe PMC] [Abstract] Cited for: C4-TYPE ZINC-FINGER OF NSP1, MUTAGENESIS OF CYS-25 AND CYS-44.
[13]	"Nuclear localization of non-structural protein 1 and nucleocapsid protein of equine arteritis virus." Tijms M.A., van der Meer Y., Snijder E.J. J. Gen. Virol. 83:795-800(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION OF NSP1 PAPAIN-LIKE CYSTEINE PROTEINASE.
[14]	"Equine arteritis virus non-structural protein 1, an essential factor for viral subgenomic mRNA synthesis, interacts with the cellular transcription co-factor p100." Tijms M.A., Snijder E.J. J. Gen. Virol. 84:2317-2322(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN SND1/P100.
[15]	"Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses." Frias-Staheli N., Giannakopoulos N.V., Kikkert M., Taylor S.L., Bridgen A., Paragas J., Richt J.A., Rowland R.R., Schmaljohn C.S., Lenschow D.J., Snijder E.J., Garcia-Sastre A., Virgin H.W. Cell Host Microbe 2:404-416(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF NSP2.
[16]	"Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase with an alpha/beta C-terminal extension and alternate conformations of the oxyanion hole." Barrette-Ng I.H., Ng K.K.-S., Mark B.L., Van Aken D., Cherney M.M., Garen C., Kolodenko Y., Gorbalenya A.E., Snijder E.J., James M.N.G. J. Biol. Chem. 277:39960-39966(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1071-1268 (NSP4).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53459 Genomic RNA. Translation: CAC42774.2.
X53459 Genomic RNA. Translation: CAC42775.2.
X52277 Genomic RNA. Translation: CAA36520.1.

PIR

RRWVEV. A39925.

RefSeq

NP_127506.1. NC_002532.2.
NP_127507.1. NC_002532.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MBM	X-ray	2.00	A/B/C/D	1071-1268	[»]
2L8K	NMR	-	A	1454-1575	[»]
4IUM	X-ray	1.45	A	261-392	[»]

ProteinModelPortal

P19811.

SMR

P19811. Positions 1071-1268.

ModBase

Search...

Protein family/group databases

MEROPS

C33.001.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

921339.

Enzyme and pathway databases

BRENDA

3.4.21.114. 6985.

Family and domain databases

Gene3D

3.30.40.20. 1 hit.

InterPro

IPR027351. (+)RNA_virus_helicase_core_dom.
IPR008743. Arterivirus_Nsp2_C33.
IPR023338. Arterivirus_NSP4_peptidase.
IPR027355. AV_MBD_dom.
IPR008741. AV_PCPalpha.
IPR025773. AV_PCPbeta.
IPR023183. Chymotrypsin-like_domain3.
IPR022230. DUF3756.
IPR008760. EAV_peptidase_S32.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF12581. DUF3756. 1 hit.
PF05412. Peptidase_C33. 1 hit.
PF05579. Peptidase_S32. 1 hit.
PF00680. RdRP_1. 1 hit.
PF01443. Viral_helicase1. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS51538. AV_CP. 1 hit.
PS51652. AV_MBD. 1 hit.
PS51493. AV_NSP4_PRO. 1 hit.
PS51539. AV_PCP_ALPHA. 1 hit.
PS51540. AV_PCP_BETA. 1 hit.
PS51657. PSRV_HELICASE. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P19811.

Entry information

Entry name

RPOA_EAVBU

Accession

Primary (citable) accession number: P19811
Secondary accession number(s): Q88625, Q8QZQ5, Q91DM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	April 13, 2004
Last modified:	May 1, 2013
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families