Q66578 (POLG_HPE1H) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 10 chains: Protein VP0 Alternative name(s): P1AB Virion protein 0 Protein VP3 Alternative name(s): P1C Virion protein 3 Protein VP1 Alternative name(s): P1D Virion protein 1 Picornain 2A Short name=P2A Short name=Protein 2A EC=3.4.22.29 Protein 2B Short name=P2B Protein 2C Short name=P2C EC=3.6.1.15 Protein 3A Short name=P3A Protein 3B Short name=P3B Alternative name(s): VPg Picornain 3C EC=3.4.22.28 Alternative name(s): Protease 3C Short name=P3C RNA-directed RNA polymerase 3D-POL Short name=P3D-POL EC=2.7.7.48
Organism	Human parechovirus 1 (strain Harris) (HPeV-1) (Echovirus 22) [Complete proteome]
Taxonomic identifier	103911 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Parechovirus › Human parechovirus › Human parechovirus 1
Virus host	Homo sapiens (Human) [TaxID: 9606] Macaca (macaques) [TaxID: 9539]

Protein attributes

Sequence length	2180 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	Capsid proteins VP0, VP2, VP3 form a closed capsid enclosing the viral positive strand RNA genome. Capsid proteins interact with host alpha-V/beta-3 integrin heterodimer to provide virion attachment target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. Ref.3 Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription By similarity. Ref.3 Protein 2B affects membrane integrity and cause an increase in membrane permeability By similarity. Ref.3 Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity. Ref.3 Protein 3A, via its hydrophobic domain, serves as membrane anchor By similarity. Ref.3 Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease By similarity. Ref.3 RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals By similarity. Ref.3
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly. NTP + H2O = NDP + phosphate.
Subcellular location	Protein VP3: Virion By similarity. Host cytoplasm Potential. Protein VP1: Virion By similarity. Host cytoplasm Potential. Protein 2B: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 2C: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 3A: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity. Protein 3B: Virion Potential. Picornain 3C: Host cytoplasm Potential. RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum By similarity.
Post-translational modification	VPg is uridylylated by the polymerase and is covalently linked to the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase By similarity. Specific enzymatic cleavages yield mature proteins. All cleavages are catalyzed by P3C. The N-terminus of VP0 is blocked.
Sequence similarities	Belongs to the picornaviruses polyprotein family. Contains 2 peptidase C3 domains. Contains 1 RdRp catalytic domain. Contains 1 SF3 helicase domain.

Ontologies

Keywords
Biological process	Clathrin-mediated endocytosis of virus by host Host-virus interaction Ion transport Transport Viral RNA replication Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
Cellular component	Host cytoplasm Host cytoplasmic vesicle Host membrane Membrane Virion
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Capsid protein Helicase Hydrolase Ion channel Nucleotidyltransferase Protease RNA-directed RNA polymerase Thiol protease Transferase Viral ion channel
PTM	Covalent protein-RNA linkage Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological_process	RNA-protein covalent cross-linking Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via clathrin-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW viral genome Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA helicase activity 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 structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	Protein VP0 Potential		PRO_0000039730
	Chain	290 – 542	253	Protein VP3 Potential		PRO_0000039731
	Chain	543 – 776	234	Protein VP1 Potential		PRO_0000039732
	Chain	777 – 923	147	Picornain 2A Potential		PRO_0000039733
	Chain	924 – 1045	122	Protein 2B Potential		PRO_0000039734
	Chain	1046 – 1374	329	Protein 2C Potential		PRO_0000039735
	Chain	1375 – 1491	117	Protein 3A Potential		PRO_0000039736
	Chain	1492 – 1511	20	Protein 3B Potential		PRO_0000039737
	Chain	1512 – 1711	200	Picornain 3C Potential		PRO_0000039738
	Chain	1712 – 2180	469	RNA-directed RNA polymerase 3D-POL Potential		PRO_0000039739
Regions
	Domain	1160 – 1318	159	SF3 helicase
	Domain	1945 – 2059	115	RdRp catalytic
	Nucleotide binding	1185 – 1192	8	ATP Potential
	Motif	764 – 766	3	Cell attachment site Potential
Sites
	Active site	1550	1	For picornain 3C activity Potential
	Active site	1581	1	For picornain 3C activity Potential
	Active site	1670	1	For picornain 3C activity Potential
	Site	776 – 777	2	Cleavage; by picornain 2A Potential
Amino acid modifications
	Modified residue	1494	1	O-(5'-phospho-RNA)-tyrosine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q66578 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 3A5F1DAC43C12DEE	FASTA	2,180	245,844
	10 20 30 40 50 60 METIKSIADM ATGVVSSVDS TINAVNEKVE SVGNEIGGNL LTKVADDASN ILGPNCFATT 70 80 90 100 110 120 AEPENKNVVQ ATTTVNTTNL TQHPSAPTMP FSPDFSNVDN FHSMAYDITT GDKNPSKLVR 130 140 150 160 170 180 LETHEWTPSW ARGYQITHVE LPKVFWDHQD KPAYGQSRYF AAVRCGFHFQ VQVNVNQGTA 190 200 210 220 230 240 GSALVVYEPK PVVTYDSKLE FGAFTNLPHV LMNLAETTQA DLCIPYVADT NYVKTDSSDL 250 260 270 280 290 300 GQLKVYVWTP LSIPTGSANQ VDVTILGSLL QLDFQNPRVF AQDVNIYDNA PNGKKKNWKK 310 320 330 340 350 360 IMTMSTKYKW TRTKIDIAEG PGSMNMANVL CTTGAQSVAL VGERAFYDPR TAGSKSRFDD 370 380 390 400 410 420 LVKIAQLFSV MADSTTPSEN HGVDAKGYFK WSATTAPQSI VHRNIVYLRL FPNLNVFVNS 430 440 450 460 470 480 YSYFRGSLVL RLSVYASTFN RGRLRMGFFP NATTDSTSTL DNAIYTICDI GSDNSFEITI 490 500 510 520 530 540 PYSFSTWMRK TNGHPIGLFQ IEVLNRLTYN SSSPSEVYCI VQGKMGQDAR FFCPTGSVVT 550 560 570 580 590 600 FQNSWGSQMD LTDPLCIEDD TENCKQTMSP NELGLTSAQD DGPLGQEKPN YFLNFRSMNV 610 620 630 640 650 660 DIFTVSHTKV DNLFGRAWFF MEHTFTNEGQ WRVPLEFPKQ GHGSLSLLFA YFTGELNIHV 670 680 690 700 710 720 LFLSERGFLR VAHTYDTSND RVNFLSSNGV ITVPAGEQMT LSAPYYSNKP LRTVRDNNSL 730 740 750 760 770 780 GYLMCKPFLT GTSTGKIEVY LSLRCPNFFF PLPAPKVTSS RALRGDMANL TNQSPYGQQP 790 800 810 820 830 840 QNRMMKLAYL DRGFYKHYGI IVGDHVYQLD SDDIFKTALT GKAKFTKTKL TSDWVIEEEC 850 860 870 880 890 900 ELDYFRIKYL ESAVDSEHIF SVDKNCETIA KDIFGTHTLS QHQAIGLVGT ILLTAGLMST 910 920 930 940 950 960 IKTPVNAVTI KEFFNHAIDG DEQGLSLLVQ KCTTFFSSAA TEILDNDLVK FIVKILVRIL 970 980 990 1000 1010 1020 CYMVLYCHKP NILTTACLST LLIMDVTSSS VLSPSCKALM QCLMDGDVKK LAEIVAESMS 1030 1040 1050 1060 1070 1080 NTDDDEVKEQ ICDTVKYTKT ILSNQGPFKG FNEVSTAFRH IDWWIHTLLK IKDMVLSVFK 1090 1100 1110 1120 1130 1140 PSIESKAIQW LERNKEHVCS ILDYASDIIV ESKDQSKMKT QDFYQRYSDC LAKFKPIMAI 1150 1160 1170 1180 1190 1200 CFRSCHNSIS NTVYRLFQEL ARIPNRISTN NDLIRIEPIG IWIQGEPGQG KSFLTHTLSR 1210 1220 1230 1240 1250 1260 QLQKSCKLNG VFTNPTASEF MDGYDNQDIH LIDDLGQTRK EKDIEMLCNC ISSVPFIVPM 1270 1280 1290 1300 1310 1320 AHLEEKGKFY TSKLVVATTN KSDFSSTVLQ DSGALKRRFP YIMHIRAAKA YSKAGKLNVS 1330 1340 1350 1360 1370 1380 QAMATMSTGE CWEVSKNGRD WETLKLKDLV DKITIDYNER VKNYNAWKQQ LENQTLDDLD 1390 1400 1410 1420 1430 1440 DAVSYIKHNF PDAIPYVDEY LNIEMSTLIE QMEAFIEPKP SVFKCFANKI GSKISKASRE 1450 1460 1470 1480 1490 1500 VVDWFSDKIK SMLSFVERNK AWLTVVSAVT SAISILLLVT KIFKKEESKD ERAYNPTLPV 1510 1520 1530 1540 1550 1560 AKPKGTFPVS QREFKNEAPY DGQLEHIISQ MAYITGSTTG HMTHCAGYQH DEIILHGHSI 1570 1580 1590 1600 1610 1620 KYLEQEDELT LHYKNKVFPI EQPSVTQVTL GGKPMDLAIL KCKLPFRFKK NSKYYTNKIG 1630 1640 1650 1660 1670 1680 TESMLIWMTE QGIITKEVQR VHHSGGIKTR EGTESTKTIS YTVKSCKGMC GGLLISKVEG 1690 1700 1710 1720 1730 1740 NFKILGMHIA GNGEMGVAIP FNFLKNDMSD QGIVTEITPI QPMYINTKTQ IHKSPVYGAV 1750 1760 1770 1780 1790 1800 EVKMGPAVLS KSDTRLEEPV ECLIKKSASK YRVNKFQVNN ELWQGVKACV KSKFREIFGM 1810 1820 1830 1840 1850 1860 NGIVDMKTAI LGTSHVNSMD LSTSAGYSFV KSGYKKKDLI CLEPFSVAPL LERLVQDKFH 1870 1880 1890 1900 1910 1920 NLLKGNQITT TFNTCLKDEL RKLDKIASGK TRCIEACEVD YCIVYRMIMM EIYDKIYQTP 1930 1940 1950 1960 1970 1980 CYYSGLAVGI NPYKDWHFMI NALNDYNYEM DYSQYDGSLS SMLLWEAVEV LAYCHDSPDL 1990 2000 2010 2020 2030 2040 VMQLHKPVID SDHVVFNERW LIHGGMPSGS PCTTVLNSLC NLMMCIYTTN LISPGIDCLP 2050 2060 2070 2080 2090 2100 IVYGDDVILS LDKEIEPEKL QSIMADSFGA EVTGSRKDEP PSLKPRMEVE FLKRKPGYFP 2110 2120 2130 2140 2150 2160 ESTFIVGKLD TENMIQHLMW MKNFSTFKQQ LQSYLMELCL HGKDTYQHYI KILEPYLQEW 2170 2180 NITVDDYDVV ITKLMPMVFD

References

[1]	"A distinct picornavirus group identified by sequence analysis." Hyypiae T., Horsnell C., Maaronen M., Khan M., Kalkkinen N., Auvinen P., Kinnunen L., Stanway G. Proc. Natl. Acad. Sci. U.S.A. 89:8847-8851(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], PROTEIN SEQUENCE OF 29-61; 67-80; 290-297 AND 543-551.
[2]	"Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group." Stanway G., Kalkinnen N., Roivainen M., Ghazi F., Khan M., Smyth M., Meurman O., Hyppiae T. J. Virol. 68:8232-8238(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 6-22; 29-61; 67-80 AND 118-131.
[3]	"Entry of human parechovirus 1." Joki-Korpela P., Marjomaki V., Krogerus C., Heino J., Hyypia T. J. Virol. 75:1958-1967(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF CAPSID PROTEINS.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L02971 Genomic RNA. Translation: AAA72291.1. S45208 Genomic RNA. Translation: AAB23363.1.
PIR	A46182.
3D structure databases
ProteinModelPortal	Q66578.
ModBase	Search...
Protein family/group databases
MEROPS	C03.023.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR004004. Helic/Pol/Pept_Calicivir-typ. IPR000605. Helicase_SF3_ssDNA/RNA_vir. IPR014759. Helicase_SF3_ssRNA_vir. IPR000199. Peptidase_C3A/C3B_picornavir. IPR001676. Picornavirus_capsid. IPR001205. RNA-dir_pol_C. IPR007094. RNA-dir_pol_PSvirus. IPR009003. Trypsin-like_Pept_dom. IPR009419. VPP_parechovir_P3A. IPR009407. VPP_parechovir_P3B. [Graphical view]
Pfam	PF06344. Parecho_VpG. 1 hit. PF00548. Peptidase_C3. 1 hit. PF06363. Picorna_P3A. 1 hit. PF00680. RdRP_1. 1 hit. PF00073. Rhv. 1 hit. PF00910. RNA_helicase. 1 hit. [Graphical view]
PRINTS	PR00918. CALICVIRUSNS.
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50507. RDRP_SSRNA_POS. 1 hit. PS51218. SF3_HELICASE_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

POLG_HPE1H

Accession

Primary (citable) accession number: Q66578
Secondary accession number(s): Q90062

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program