Q9ELS8 (Q9ELS8_9HEPC) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names	Recommended name: Genome polyprotein RuleBase RU003358
Organism	Hepatitis C virus subtype 1a EMBL AAG02099.1
Taxonomic identifier	31646 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Hepacivirus

Protein attributes

Sequence length	3011 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + H2O = ADP + phosphate. SAAS SAAS007094 NTP + H2O = NDP + phosphate. SAAS SAAS007094 Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). SAAS SAAS007094
Sequence similarities	Contains 1 RdRp catalytic domain. SAAS SAAS007094

Ontologies

Keywords
Biological process	Host-virus interaction Initiation of viral infection RNA replication SAAS SAAS007094 Viral attachment to host cell SAAS SAAS007094
Cellular component	Host membrane SAAS SAAS007094 Membrane Viral envelope protein RuleBase RU000330 Virion
Domain	Transmembrane Transmembrane helix SAAS SAAS007094
Ligand	ATP-binding Metal-binding PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX Nucleotide-binding RNA-binding RuleBase RU000330 Viral nucleoprotein RuleBase RU000330 Zinc PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX
Molecular function	Capsid protein RuleBase RU000330 SAAS SAAS007094 Helicase SAAS SAAS007094 Hydrolase Nucleotidyltransferase Protease SAAS SAAS011492 RNA-directed RNA polymerase SAAS SAAS007094 Ribonucleoprotein RuleBase RU000330 Transferase
PTM	Glycoprotein RuleBase RU000330
Technical term	3D-structure PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: InterPro evasion by virus of host immune response Inferred from electronic annotation. Source: InterPro proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro transformation of host cell by virus Inferred from electronic annotation. Source: InterPro viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: InterPro host cell membrane Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW ribonucleoprotein complex Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro 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 serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type exopeptidase activity Inferred from electronic annotation. Source: InterPro structural molecule activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Sites
	Metal binding	1123	1	Zinc PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX
	Metal binding	1124	1	Zinc; via carbonyl oxygen PDB 2OC7
	Metal binding	1125	1	Zinc PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX
	Metal binding	1171	1	Zinc PDB 2FM2 PDB 2O8M PDB 2OBO PDB 2OBQ PDB 2OC0 PDB 2OC1 PDB 2OC7 PDB 2OC8 PDB 3KNX PDB 3LON PDB 3LOX

Sequences

	Sequence		Length	Mass (Da)
	Q9ELS8 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: A6BECF5A3B3EE13F	FASTA	3,011	327,111
	10 20 30 40 50 60 MSTNPKPQRK TKRNTNRRPQ DVKFPGGGQI VGGVYLLPRR GPRLGVRATR KTSERSQPRG 70 80 90 100 110 120 RRQPIPKARR PEGRTWAQPG YPWPLYGNEG CGWAGWLLSP RGSRPSWGPT DPRRRSRNLG 130 140 150 160 170 180 KVIDTLTCGF ADLMGYIPLV GAPLGGAARA LAHGVRVLED GVNYATGNLP GCSFSIFLLA 190 200 210 220 230 240 LLSCLTVPAS AYQVRNSSGL YHVTNDCPNS SIVYEAADAI LHTPGCVPCV REGNASRCWV 250 260 270 280 290 300 AVTPTVATRD GKLPTTQLRR HIDLLVGSAT LCSALYVGDL CGSVFLVGQL FTFSPRRHWT 310 320 330 340 350 360 TQDCNCSIYP GHITGHRMAW DMMMNWSPTA ALVVAQLLRI PQAILDMIAG AHWGVLAGIA 370 380 390 400 410 420 YFSMVGNWAK VLVVLLLFAG VDAETHVTGG SAGHTTAGLV RLLSPGAKQN IQLINTNGSW 430 440 450 460 470 480 HINSTALNCN ESLNTGWLAG LFYHHKFNSS GCPERLASCR RLTDFAQGGG PISYANGSGL 490 500 510 520 530 540 DERPYCWHYP PRPCGIVPAK SVCGPVYCFT PSPVVVGTTD RSGAPTYSWG ANDTDVFVLN 550 560 570 580 590 600 NTRPPLGNWF GCTWMNSTGF TKVCGAPPCV IGGVGNNTLL CPTDCFRKHP EATYSRCGSG 610 620 630 640 650 660 PWITPRCMVD YPYRLWHYPC TINYTIFKVR MYVGGVEHRL EAACNWTRGE RCDLEDRDRS 670 680 690 700 710 720 ELSPLLLSTT QWQVLPCSFT TLPALSTGLI HLHQNIVDVQ YLYGVGSSIA SWAIKWEYVV 730 740 750 760 770 780 LLFLLLADAR VCSCLWMMLL ISQAEAALEN LVILNAASLA GTHGFVSFLV FFCFAWYLKG 790 800 810 820 830 840 RWVPGAAYAL YGIWPLLLLL LALPQRAYAL DTEVAASCGG VVLVGLMALT LSPYYKRYIS 850 860 870 880 890 900 WCMWWLQYFL TRVEAQLHVW VPPLNVRGGR DAVILLMCAV HPTLVFDITK LLLAIFGPLW 910 920 930 940 950 960 ILQASLLKVP YFVRVQGLLR ICALARKIAG GHYVQMIFIK LGALTGTYVY NHLTPLRDWA 970 980 990 1000 1010 1020 HNGLRDLAVA VEPVVFSRME TKLITWGADT AACGDIINGL PVSARRGQEI LLGPADGMVS 1030 1040 1050 1060 1070 1080 KGWRLLAPIT AYAQQTRGLL GCIITSLTGR DKNQVEGEVQ IVSTATQTFL ATCINGVCWT 1090 1100 1110 1120 1130 1140 VYHGAGTRTI ASPKGPVIQM YTNVDQDLVG WPAPQGSRSL TPCTCGSSDL YLVTRHADVI 1150 1160 1170 1180 1190 1200 PVRRQGDSRG SLLSPRPISY LKGSSGGPLL CPAGHAVGLF RAAVCTRGVA KAVDFIPVEN 1210 1220 1230 1240 1250 1260 LETTMRSPVF TDNSSPPAVP QSFQVAHLHA PTGSGKSTKV PAAYAAQGYK VLVLNPSVAA 1270 1280 1290 1300 1310 1320 TLGFGAYMSK AHGVDPNIRT GVRTITTGSP ITYSTYGKFL ADGGCSGGAY DIIICDECHS 1330 1340 1350 1360 1370 1380 TDATSILGIG TVLDQAETAG ARLVVLATAT PPGSVTVPHP NIEEVALSTT GEIPFYGKAI 1390 1400 1410 1420 1430 1440 PLEVIKGGRH LIFCHSKKKC DELAAKLVAL GINAVAYYRG LDVSVIPASG DVVVVSTDAL 1450 1460 1470 1480 1490 1500 MTGFTGDFDP VIDCNTCVTQ TVDFSLDPTF TIETTTLPQD AVSRTQRRGR TGRGKPGIYR 1510 1520 1530 1540 1550 1560 FVAPGERPSG MFDSSVLCEC YDAGCAWYEL TPAETTVRLR AYMNTPGLPV CQDHLEFWEG 1570 1580 1590 1600 1610 1620 VFTGLTHIDA HFLSQTKQSG ENFPYLVAYQ ATVCARAQAP PPSWDQMWKC LIRLKPTLHG 1630 1640 1650 1660 1670 1680 PTPLLYRLGA VQNEITLTHP VTKYIMTCMS ANPEVVTSTW VLVGGVLAAL AAYCLSTGCV 1690 1700 1710 1720 1730 1740 VIVGRIVLSG KPAIIPDREV LYQEFDEMEE CSQHLPYIEQ GMMLAEQFKQ EALGLLQTAS 1750 1760 1770 1780 1790 1800 RQAEVITPAV QTNWQKLEAF WAKHMWNFIS GTQYLAGLST LPGNPAIASL MAFTAAVTSP 1810 1820 1830 1840 1850 1860 LTTSQTLLFN ILGGWVAAQL AAPGAATAFV GAGLAGAAIG SVGLGKVLVD ILAGYGAGVA 1870 1880 1890 1900 1910 1920 GALVAFKIMS GEVPSTEDLV NLLPAILSPG ALVVGVVCAA ILRRHVGPGE GAVQWMNRLI 1930 1940 1950 1960 1970 1980 AFASRGNHVS PTHYVPESDA AARVTAILSN LTVTQLLRRL HQWIGSECTT PCSGSWLRDI 1990 2000 2010 2020 2030 2040 WDWICEVLSD FKTWLKAKLM PQLPGIPFVS CQRGYRGVWR GDGIMHTRCH CGAEITGHVK 2050 2060 2070 2080 2090 2100 NGTMRIVGPR TCRNMWSGTF PINAYTTGPC TPLPAPNYKF ALWRVSAEEY VEIRRVGDFH 2110 2120 2130 2140 2150 2160 YVSGMTTDNL KCPCQIPSPE FFTELDGVRL HRFAPPCKPL LREEVSFRVG LHEYPVGSQL 2170 2180 2190 2200 2210 2220 PCEPEPDVAV LTSMLTDPSH ITAEAAGRRL ARGSPPSMAS SSASQLSAPS LKATCTTNHD 2230 2240 2250 2260 2270 2280 SPDAELIEAN LLWRQEMGGN ITRVESENKV VILDSFDPLV AEEDEREVSV PAEILRKSQR 2290 2300 2310 2320 2330 2340 FARALPVWAR PDYNPPLIET WKEPDYEPPV VHGCPLPPPR SPPVPPPRKK RTVVLTESTL 2350 2360 2370 2380 2390 2400 STALAELATK SFGSSSTSGI TGDNTTTSSE PAPSGCPPDS DVESYSSMPP LEGEPGDPDF 2410 2420 2430 2440 2450 2460 SDGSWSTVSS GADTEDVVCC SMSYSWTGAL VTPCAAEEQK LPINALSNSL LRHHNLVYST 2470 2480 2490 2500 2510 2520 TSRSACQRQK KVTFDRLQVL DSHYQDVLKE VKAAASRVKA NLLSVEEACS LTPPHSAKSK 2530 2540 2550 2560 2570 2580 FGYGAKDVRC HARKAVAHIN SVWKDLLEDS VTPIDTTIMA KNEVFCVQPE KGGRKPARLI 2590 2600 2610 2620 2630 2640 VFPDLGVRVC EKMALYDVVS KLPLAVMGSS YGFQYSPGQR VEFLVQAWKS KKTPMGFSYD 2650 2660 2670 2680 2690 2700 TRCFDSTVTE SDIRTEEAIY QCCDLDPQAR VAIKSLTERL YVGGPLTNSR GENCGYRRCR 2710 2720 2730 2740 2750 2760 ASGVLTTSCG NTLTCYIKAR AACRAAGLQD RTMLVCGDDL VVICESAGVQ EDAASLRAFT 2770 2780 2790 2800 2810 2820 EAMTRYSAPP GDPPQPEYDL ELITSCSSNV SVAHDGAGKR VYYLTRDPTT PLARAAWETA 2830 2840 2850 2860 2870 2880 RHTPVNSWLG NIIMFAPTLW ARMILMTHFF SVLIARDQFE QALNCEIYGA CYSIEPLDLP 2890 2900 2910 2920 2930 2940 PIIQRLHGLS AFSLHSYSPG EINRVAACLR KLGVPPLRAW KHRARSVRAR LLSRGGRAAI 2950 2960 2970 2980 2990 3000 CGKYLFNWAV RTKPKLTPIA AAGRLDLSGW FTAGYSGGDI YHSVSHARPR WSWFCLLLLA 3010 AGVGIYLLPN R

References

[1]	"Hepatitis C Virus." Desai S.M., Devare S., Yamaguchi J. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: Colonel EMBL AAG02099.1.
[2]	"Interaction of immune sera with synthetic peptides corresponding to the structural protein region of hepatitis C virus." Ching W.M., Wychowski C., Beach M.J., Wang H., Davies C.L., Carl M., Bradley D.W., Alter H.J., Feinstone S.M., Shih J.W. Proc. Natl. Acad. Sci. U.S.A. 89:3190-3194(1992) [PubMed: 1373489] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[3]	"Sequence variability in the 5' non-coding region of hepatitis C virus: identification of a new virus type and restrictions on sequence diversity." Simmonds P., McOmish F., Yap P.L., Chan S.W., Lin C.K., Dusheiko G., Saeed A.A., Holmes E.C. J. Gen. Virol. 74:661-668(1993) [PubMed: 8385694] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[4]	"Mutations conferring resistance to SCH6, a novel hepatitis C virus NS3/4A protease inhibitor. Reduced RNA replication fitness and partial rescue by second-site mutations." Yi M., Tong X., Skelton A., Chase R., Chen T., Prongay A., Bogen S.L., Saksena A.K., Njoroge F.G., Veselenak R.L., Pyles R.B., Bourne N., Malcolm B.A., Lemon S.M. J. Biol. Chem. 281:8205-8215(2006) [PubMed: 16352601] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1027-1207 AND 1680-1696 IN COMPLEX WITH ZINC.
[5]	"Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure-based optimization." Prongay A.J., Guo Z., Yao N., Pichardo J., Fischmann T., Strickland C., Myers J., Weber P.C., Beyer B.M., Ingram R., Hong Z., Prosise W.W., Ramanathan L., Taremi S.S., Yarosh-Tomaine T., Zhang R., Senior M., Yang R.S. , Malcolm B., Arasappan A., Bennett F., Bogen S.L., Chen K., Jao E., Liu Y.T., Lovey R.G., Saksena A.K., Venkatraman S., Girijavallabhan V., Njoroge F.G., Madison V. J. Med. Chem. 50:2310-2318(2007) [PubMed: 17444623] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1027-1207 IN COMPLEX WITH ZINC.
[6]	"Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 protease." Venkatraman S., Velazquez F., Wu W., Blackman M., Chen K.X., Bogen S., Nair L., Tong X., Chase R., Hart A., Agrawal S., Pichardo J., Prongay A., Cheng K.C., Girijavallabhan V., Piwinski J., Shih N.Y., Njoroge F.G. J. Med. Chem. 52:336-346(2009) [PubMed: 19102654] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1027-1207 AND 1680-1696 IN COMPLEX WITH ZINC.
[7]	"Candidate selection and preclinical evaluation culminating in the discovery of Narlaprevir (SCH 900518): A potent, selective and orally efficacious second generation HCV NS3 serine protease inhibitor." Arasappan A., Bennett F., Bogen S.L., Blackman M., Chen K., Hendrata S., Huang Y., Huelgas R.M., Nair L., Padilla A.I., Pan W., Pike R., Pinto P., Ruan S., Sannigrahi M., Velaquez F., Vibulbhan B., Wu W. , Yang W., Saksena A.K., Girijavallabhan V., Shih N.Y., Kong J., Meng T., Jin Y., Wong J., McNamara P., Prongay A., Madison V., Piwinski J.J., Cheng K.C., Morrison R., Malcolm B., Tong X., Ralston R., Njoroge F.G. Submitted (FEB-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1027-1207 IN COMPLEX WITH ZINC.
[8]	"The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitor." Bennett F., Huang Y., Hendrata S., Lovey R., Bogen S.L., Pan W., Guo Z., Prongay A., Chen K.X., Arasappan A., Venkatraman S., Velazquez F., Nair L., Sannigrahi M., Tong X., Pichardo J., Cheng K.C., Girijavallabhan V.M., Saksena A.K., Njoroge F.G. Bioorg. Med. Chem. Lett. 20:2617-2621(2010) [PubMed: 20303756] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 1027-1207 IN COMPLEX WITH ZINC.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF290978 Genomic RNA. Translation: AAG02099.1.

PIR

A44150.
PQ0804.
PS0326.
PS0327.
PS0328.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FM2	X-ray	2.70	A/C	1027-1207	[»]
			B/D	1680-1696	[»]
2O8M	X-ray	2.00	A/B	1027-1207	[»]
2OBO	X-ray	2.60	A/C	1027-1207	[»]
2OBQ	X-ray	2.50	A/C	1027-1207	[»]
2OC0	X-ray	2.30	A/C	1027-1207	[»]
2OC1	X-ray	2.70	A/C	1027-1207	[»]
2OC7	X-ray	2.70	A/C	1027-1207	[»]
2OC8	X-ray	2.66	A/C	1027-1207	[»]
3KNX	X-ray	2.65	A/C	1027-1207	[»]
			B/D	1680-1696	[»]
3LON	X-ray	2.20	A/C	1027-1207	[»]
3LOX	X-ray	2.65	A/C	1027-1207	[»]

ProteinModelPortal

Q9ELS8.

SMR

Q9ELS8. Positions 2-45, 902-1026, 1029-1657, 1973-2003, 2008-2170, 2421-2982.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

euHCVdb

AF290978.

Family and domain databases

InterPro

IPR014001. DEAD-like_helicase.
IPR011492. DEAD_Flavivir.
IPR002521. HCV_core_C.
IPR002522. HCV_core_N.
IPR002519. HCV_env.
IPR002531. HCV_NS1.
IPR000745. HCV_NS4a.
IPR001490. HCV_NS4b.
IPR002868. HCV_NS5a.
IPR013193. HCV_NS5a_1B_dom.
IPR024350. HCV_NS5a_C.
IPR001650. Helicase_C.
IPR002518. Pept_C18_HCV_NS2.
IPR009003. Pept_cys/ser_Trypsin-like.
IPR004109. Peptidase_S29.
IPR007094. RNA-dir_pol_PSvirus.
IPR002166. RNA_pol_HCV.
IPR013192. Znf_HCV_NS5a.
[Graphical view]

Pfam

PF07652. Flavi_DEAD. 1 hit.
PF01543. HCV_capsid. 1 hit.
PF01542. HCV_core. 1 hit.
PF01539. HCV_env. 1 hit.
PF01560. HCV_NS1. 1 hit.
PF01538. HCV_NS2. 1 hit.
PF01006. HCV_NS4a. 1 hit.
PF01001. HCV_NS4b. 1 hit.
PF01506. HCV_NS5a. 1 hit.
PF08300. HCV_NS5a_1a. 1 hit.
PF08301. HCV_NS5a_1b. 1 hit.
PF12941. HCV_NS5a_C. 1 hit.
PF02907. Peptidase_S29. 1 hit.
PF00998. RdRP_3. 1 hit.
[Graphical view]

ProDom

PD001388. HCV_env. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00487. DEXDc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

Q9ELS8_9HEPC

Accession

Primary (citable) accession number: Q9ELS8

Entry history

Integrated into UniProtKB/TrEMBL:	March 1, 2001
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)