P08617 (POLG_HAVHM) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 18 chains: Protein VP0 Alternative name(s): VP4-VP2 Protein VP4 Alternative name(s): P1A Virion protein 4 Protein VP2 Alternative name(s): P1B Virion protein 2 Protein VP3 Alternative name(s): P1C Virion protein 3 Protein VP1-2A Alternative name(s): PX Protein VP1 Alternative name(s): P1D Virion protein 1 Protein 2A Short name=P2A Protein 2BC Protein 2B Short name=P2B Protein 2C Short name=P2C EC=3.6.1.15 Protein 3ABCD Short name=P3 Protein 3ABC Protein 3AB Protein 3A Short name=P3A Protein 3B Short name=P3B Alternative name(s): VPg Protein 3CD 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 hepatitis A virus genotype IB (isolate HM175) (HHAV) (Human hepatitis A virus (isolate Human/Australia/HM175/1976)) [Reference proteome]
Taxonomic identifier	12098 [NCBI]
Taxonomic lineage	Viruses › ssRNA viruses › ssRNA positive-strand viruses, no DNA stage › Picornavirales › Picornaviridae › Hepatovirus › Hepatitis A virus › Human hepatitis A virus
Virus host	Cercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey) [TaxID: 9536] Homo sapiens (Human) [TaxID: 9606] Macaca (macaques) [TaxID: 9539] Pan troglodytes (Chimpanzee) [TaxID: 9598]

Protein attributes

Sequence length	2227 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 VP1, VP2, and VP3 form a closed capsid enclosing the viral positive strand RNA genome. All these proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with HAVCR1 to provide virion attachment to target cell By similarity. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 VP0 precursor is a component of immature procapsids. The N-terminal domain of VP0, protein VP4, is needed for the assembly of 12 pentamers into the icosahedral structure. Unlike other picornaviruses, HAV VP4 does not seem to be myristoylated and has not been detected in mature virions, supposedly owing to its small size. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 VP1-2A precursor is a component of immature procapsids and corresponds to an extended form of the structural protein VP1. The C-terminal domain of VP1-2A, protein 2A, acts as an assembly signal that allows pentamerization of P1-2A, which is the precursor of the structural proteins. 2A is proteolytically removed from particulate VP1-2A by a host protease and does not seem to be found in mature particles. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 Protein 2B and 2BC precursor affect membrane integrity and cause an increase in membrane permeability. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities By similarity. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 Protein 3A, via its hydrophobic domain, serves as membrane anchor to the 3AB and 3ABC precursors. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 The 3AB precursor interacts with the 3CD precursor and with RNA structures found at both the 5'- and 3'-termini of the viral genome. Since the 3AB precursor contains the hydrophobic domain 3A, it probably anchors the whole viral replicase complex to intracellular membranes on which viral RNA synthesis occurs. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 The 3ABC precursor is targeted to the mitochondrial membrane where protease 3C activity cleaves and inhibits the host antiviral protein MAVS, thereby disrupting activation of IRF3 through the IFIH1/MDA5 pathway. In vivo, the protease activity of 3ABC precursor is more efficient in cleaving the 2BC precursor than that of protein 3C. The 3ABC precursor may therefore play a role in the proteolytic processing of the polyprotein. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 Protein 3B is covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. It acts as a genome-linked replication primer. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 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. Also cleaves host proteins such as PCBP2. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24 RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.24
Catalytic activity	Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). 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.
Subunit structure	3AB precursor is a homodimer. 3AB precursor interacts with 3CD precursor. Protein 3ABC interacts with human MAVS. Ref.16 Ref.17 Ref.22 Ref.24
Subcellular location	Protein VP2: Virion. Host cytoplasm Potential Ref.14 Ref.24. Protein VP3: Virion. Host cytoplasm Potential Ref.14 Ref.24. Protein VP1: Virion. Host cytoplasm Potential Ref.14 Ref.24. Protein VP1-2A: Virion. Host cytoplasm Potential Ref.14 Ref.24. 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. Ref.14 Ref.24 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. May associate with membranes through a N-terminal amphipathic helix. Ref.14 Ref.24 Protein 3ABC: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Host mitochondrion outer 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. Ref.14 Ref.24 Protein 3AB: 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. Ref.14 Ref.24 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. Ref.14 Ref.24 Protein 3B: Virion Potential Ref.14 Ref.24. Picornain 3C: Host cytoplasm Potential Ref.14 Ref.24. RNA-directed RNA polymerase 3D-POL: Host cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side Potential. Note: Interacts with membranes in a complex with viral protein 3AB. 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. Ref.14 Ref.24
Post-translational modification	Specific enzymatic cleavages by viral protease in vivo yield a variety of precursors and mature proteins. Polyprotein processing intermediates are produced, such as P1-2A which is a functional precursor of the structural proteins, VP0 which is a VP4-VP2 precursor, VP1-2A precursor, 3ABC precursor which is a stable and catalytically active precursor of 3A, 3B and 3C proteins, 3AB and 3CD precursors. The assembly signal 2A is removed from VP1-2A by a host protease. During virion maturation, non-infectious particles are rendered infectious following cleavage of VP0. This maturation cleavage is followed by a conformational change of the particle. 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.
Miscellaneous	Wild-type HM175 (HM175/wt) comes from a sample isolated from a patient in Australia in 1976 and subsequently passaged three times in marmosets. HM175/7 is an attenuated strain derived from HM175 by 32 passages in African green monkey kidney cells. HM175/18f, HM175/24a, and HM175/43c are cytopathic isolates derived from HM175 by serial passages in FRhK-4 cells. Mutations in proteins 2B and 2C seem to be essential for strain HM175 adaptation to growth in cell culture.
Sequence similarities	Belongs to the picornaviridae polyprotein family. Contains 1 peptidase C3 domain. Contains 1 RdRp catalytic domain. Contains 1 SF3 helicase domain.
Caution	It is uncertain whether Met-1 or Met-3 is the initiator. In vitro, both are used, with a preference for Met-3. Protein VP1 seems to have a heterogeneous C-terminus in cell culture. It may be reduced by a few amino acids compared to the sequence shown.
Sequence caution	The sequence AAA45466.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Inhibition of host IFN-mediated response initiation by virus Inhibition of host MAVS by virus Inhibition of host innate immune response by virus Interferon antiviral system evasion Ion transport Transport Viral RNA replication Viral attachment to host cell Viral immunoevasion Virus entry into host cell
Cellular component	Host cytoplasm Host cytoplasmic vesicle Host membrane Host mitochondrion Host mitochondrion outer membrane Membrane Virion
Domain	Coiled coil
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 Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
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 suppression by virus of host MAVS activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon production 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 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 host cell mitochondrial outer 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
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 – 2227

2227

Genome polyprotein

PRO_0000308969

Chain

1 – 245

245

Protein VP0 Potential

PRO_0000308970

Chain

1 – 23

23

Protein VP4 Potential

PRO_0000039946

Chain

24 – 245

222

Protein VP2 Potential

PRO_0000039947

Chain

246 – 491

246

Protein VP3 Potential

PRO_0000039948

Chain

492 – 836

345

Protein VP1-2A Potential

PRO_0000308971

Chain

492 – 769

278

Protein VP1 Potential

PRO_0000039949

Chain

770 – 836

67

Protein 2A Potential

PRO_0000039950

Chain

837 – 1422

586

Protein 2BC Potential

PRO_0000308972

Chain

837 – 1087

251

Protein 2B Potential

PRO_0000039951

Chain

1088 – 1422

335

Protein 2C Potential

PRO_0000039952

Chain

1423 – 2227

805

Protein 3ABCD Potential

PRO_0000308973

Chain

1423 – 1738

316

Protein 3ABC Potential

PRO_0000308974

Chain

1423 – 1519

97

Protein 3AB Potential

PRO_0000308975

Chain

1423 – 1496

74

Protein 3A Potential

PRO_0000039953

Chain

1497 – 1519

23

Protein 3B Potential

PRO_0000039954

Chain

1520 – 2227

708

Protein 3CD Potential

PRO_0000308976

Chain

1520 – 1738

219

Picornain 3C Potential

PRO_0000039955

Chain

1739 – 2227

489

RNA-directed RNA polymerase 3D-POL Potential

PRO_0000039956

Regions

Topological domain

1 – 1467

1467

Cytoplasmic Potential

Intramembrane

1468 – 1482

15

Potential

Topological domain

1483 – 2227

745

Cytoplasmic Potential

Domain

1204 – 1366

163

SF3 helicase

Domain

1520 – 1716

197

Peptidase C3

Domain

1976 – 2097

122

RdRp catalytic

Nucleotide binding

1230 – 1237

8

ATP Potential

Coiled coil

1127 – 1152

26

Potential

Sites

Active site

1563

1

For picornain 3C activity

Active site

1603

1

For picornain 3C activity

Active site

1691

1

For picornain 3C activity

Site

23 – 24

2

Cleavage Potential

Site

245 – 246

2

Cleavage; by picornain 3C Potential

Site

491 – 492

2

Cleavage; by picornain 3C Potential

Site

769 – 770

2

Cleavage; by host Potential

Site

769

1

Important for VP1 folding and capsid assembly

Site

836 – 837

2

Cleavage; by picornain 3C

Site

1087 – 1088

2

Cleavage; by picornain 3C Potential

Site

1422 – 1423

2

Cleavage; by picornain 3C Potential

Site

1496 – 1497

2

Cleavage; by picornain 3C Potential

Site

1519 – 1520

2

Cleavage; by picornain 3C Potential

Site

1738 – 1739

2

Cleavage; by picornain 3C

Amino acid modifications

Modified residue

1499

1

O-(5'-phospho-RNA)-tyrosine By similarity

Natural variations

Natural variant

77

1

K → R in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

315

1

D → A in strain: HM175/24a and HM175/43c.

Natural variant

336

1

T → K in strain: HM175/18f.

Natural variant

638

1

I → V in strain: HM175/24a.

Natural variant

688

1

N → S in strain: HM175/24a and HM175/43c.

Natural variant

762

1

S → P in strain: HM175/18f.

Natural variant

764

1

E → V in strain: HM175/7.

Natural variant

767

1

M → V in strain: HM175/24a and HM175/43c.

Natural variant

821

1

N → S in strain: HM175/7.

Natural variant

838

1

K → N in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

849

1

I → M in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

941

1

D → E in 24.

Natural variant

993

1

D → H in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1052

1

A → V in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

1062

1

G → A in strain: HM175/7.

Natural variant

1109 – 1111

3

AIY → GIC in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1118

1

K → M in strain: HM175/7.

Natural variant

1151

1

E → K in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

1163

1

F → S in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

1180

1

H → Y in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1212

1

S → F in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1229

1

Y → H in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1277

1

V → I in strain: HM175/7.

Natural variant

1407

1

E → D in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1428

1

Missing in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1480

1

F → V in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1487

1

R → H in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1500

1

H → Y in strain: HM175/7.

Natural variant

1507

1

Q → H in strain: HM175/18f, HM175/24a and HM175/43c.

Natural variant

1524

1

I → V in strain: HM175/43c.

Natural variant

1620

1

Q → E in strain: HM175/18f and HM175/24a.

Natural variant

1675

1

T → A in strain: HM175/43c.

Natural variant

1805

1

D → G in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

1930

1

S → T in strain: HM175/7, HM175/18f, HM175/24a and HM175/43c.

Natural variant

1962

1

R → K in strain: HM175/18f, HM175/24a and HM175/43c.

Experimental info

Mutagenesis

769

1

R → M: Complete loss of viral particles assembly. Ref.22

Mutagenesis

836

1

Q → N: Partial loss of 2A-2B cleavage. Ref.5

Mutagenesis

836

1

Q → R: Complete loss of 2A-2B cleavage. Ref.5

Mutagenesis

1671

1

T → A: Complete loss of enzymatic activity.

Mutagenesis

1691

1

C → A: Complete loss of proteolytic activity. Ref.23

Sequence conflict

1825

1

D → V in AAA45476. Ref.4

Sequence conflict

1850

1

G → R in AAA45476. Ref.4

Sequence conflict

1856

1

E → G in AAA45476. Ref.4

Secondary structure

1

.

.

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2227

Helix Strand Turn

Details...

Helix

1521 – 1531

11

Beta strand

1532 – 1539

8

Beta strand

1545 – 1555

11

Beta strand

1557 – 1561

5

Helix

1562 – 1564

3

Turn

1565 – 1567

3

Helix

1571 – 1573

3

Beta strand

1574 – 1580

7

Beta strand

1583 – 1588

6

Helix

1589 – 1591

3

Beta strand

1592 – 1595

4

Beta strand

1597 – 1600

4

Beta strand

1603 – 1608

6

Helix

1619 – 1621

3

Helix

1625 – 1630

6

Turn

1631 – 1633

3

Beta strand

1636 – 1642

7

Beta strand

1645 – 1651

7

Beta strand

1655 – 1665

11

Beta strand

1667 – 1669

3

Beta strand

1671 – 1683

13

Beta strand

1694 – 1698

5

Helix

1700 – 1702

3

Beta strand

1706 – 1714

9

Beta strand

1717 – 1722

6

Helix

1725 – 1730

6

Sequences

	Sequence		Length	Mass (Da)
	P08617 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: 01E225E7AEB740A6	FASTA	2,227	251,508
	10 20 30 40 50 60 MNMSRQGIFQ TVGSGLDHIL SLADIEEEQM IQSVDRTAVT GASYFTSVDQ SSVHTAEVGS 70 80 90 100 110 120 HQVEPLRTSV DKPGSKKTQG EKFFLIHSAD WLTTHALFHE VAKLDVVKLL YNEQFAVQGL 130 140 150 160 170 180 LRYHTYARFG IEIQVQINPT PFQQGGLICA MVPGDQSYGS IASLTVYPHG LLNCNINNVV 190 200 210 220 230 240 RIKVPFIYTR GAYHFKDPQY PVWELTIRVW SELNIGTGTS AYTSLNVLAR FTDLELHGLT 250 260 270 280 290 300 PLSTQMMRNE FRVSTTENVV NLSNYEDARA KMSFALDQED WKSDPSQGGG IKITHFTTWT 310 320 330 340 350 360 SIPTLAAQFP FNASDSVGQQ IKVIPVDPYF FQMTNTNPDQ KCITALASIC QMFCFWRGDL 370 380 390 400 410 420 VFDFQVFPTK YHSGRLLFCF VPGNELIDVS GITLKQATTA PCAVMDITGV QSTLRFRVPW 430 440 450 460 470 480 ISDTPYRVNR YTKSAHQKGE YTAIGKLIVY CYNRLTSPSN VASHVRVNVY LSAINLECFA 490 500 510 520 530 540 PLYHAMDVTT QVGDDSGGFS TTVSTEQNVP DPQVGITTMK DLKGKANRGK MDVSGVQAPV 550 560 570 580 590 600 GAITTIEDPV LAKKVPETFP ELKPGESRHT SDHMSIYKFM GRSHFLCTFT FNSNNKEYTF 610 620 630 640 650 660 PITLSSTSNP PHGLPSTLRW FFNLFQLYRG PLDLTIIITG ATDVDGMAWF TPVGLAVDTP 670 680 690 700 710 720 WVEKESALSI DYKTALGAVR FNTRRTGNIQ IRLPWYSYLY AVSGALDGLG DKTDSTFGLV 730 740 750 760 770 780 SIQIANYNHS DEYLSFSCYL SVTEQSEFYF PRAPLNSNAM LSTESMMSRI AAGDLESSVD 790 800 810 820 830 840 DPRSEEDKRF ESHIECRKPY KELRLEVGKQ RLKYAQEELS NEVLPPPRKM KGLFSQAKIS 850 860 870 880 890 900 LFYTEEHEIM KFSWRGVTAD TRALRRFGFS LAAGRSVWTL EMDAGVLTGR LIRLNDEKWT 910 920 930 940 950 960 EMKDDKIVSL IEKFTSNKYW SKVNFPHGML DLEEIAANSK DFPNMSETDL CFLLHWLNPK 970 980 990 1000 1010 1020 KINLADRMLG LSGVQEIKEQ GVGLIAECRT FLDSIAGTLK SMMFGFHHSV TVEIINTVLC 1030 1040 1050 1060 1070 1080 FVKSGILLYV IQQLNQDEHS HIIGLLRVMN YADIGCSVIS CGKVFSKMLE TVFNWQMDSR 1090 1100 1110 1120 1130 1140 MMELRTQSFS NWLRDICSGI TIFKNFKDAI YWLYTKLKDF YEVNYGKKKD ILNILKDNQQ 1150 1160 1170 1180 1190 1200 KIEKAIEEAD EFCILQIQDV EKFEQYQKGV DLIQKLRTVH SMAQVDPNLM VHLSPLRDCI 1210 1220 1230 1240 1250 1260 ARVHQKLKNL GSINQAMVTR CEPVVCYLYG KRGGGKSLTS IALATKICKH YGVEPEKNIY 1270 1280 1290 1300 1310 1320 TKPVASDYWD GYSGQLVCII DDIGQNTTDE DWSDFCQLVS GCPMRLNMAS LEEKGRHFSS 1330 1340 1350 1360 1370 1380 PFIIATSNWS NPSPKTVYVK EAIDRRLHFK VEVKPASFFK NPHNDMLNVN LAKTNDAIKD 1390 1400 1410 1420 1430 1440 MSCVDLIMDG HNVSLMDLLS SLVMTVEIRK QNMTEFMELW SQGISDDDND SAVAEFFQSF 1450 1460 1470 1480 1490 1500 PSGEPSNSKL SGFFQSVTNH KWVAVGAAVG ILGVLVGGWF VYKHFSRKEE EPIPAEGVYH 1510 1520 1530 1540 1550 1560 GVTKPKQVIK LDADPVESQS TLEIAGLVRK NLVQFGVGEK NGCVRWVMNA LGVKDDWLLV 1570 1580 1590 1600 1610 1620 PSHAYKFEKD YEMMEFYFNR GGTYYSISAG NVVIQSLDVG FQDVVLMKVP TIPKFRDITQ 1630 1640 1650 1660 1670 1680 HFIKKGDVPR ALNRLATLVT TVNGTPMLIS EGPLKMEEKA TYVHKKNDGT TVDLTVDQAW 1690 1700 1710 1720 1730 1740 RGKGEGLPGM CGGALVSSNQ SIQNAILGIH VAGGNSILVA KLVTQEMFQN IDKKIESQRI 1750 1760 1770 1780 1790 1800 MKVEFTQCSM NVVSKTLFRK SPIYHHIDKT MINFPAAMPF SKAEIDPMAV MLSKYSLPIV 1810 1820 1830 1840 1850 1860 EEPEDYKEAS IFYQNKIVGK TQLVDDFLDL DMAITGAPGI DAINMDSSPG FPYVQEKLTK 1870 1880 1890 1900 1910 1920 RDLIWLDENG LLLGVHPRLA QRILFNTVMM ENCSDLDVVF TTCPKDELRP LEKVLESKTR 1930 1940 1950 1960 1970 1980 AIDACPLDYS ILCRMYWGPA ISYFHLNPGF HTGVAIGIDP DRQWDELFKT MIRFGDVGLD 1990 2000 2010 2020 2030 2040 LDFSAFDASL SPFMIREAGR IMSELSGTPS HFGTALINTI IYSKHLLYNC CYHVCGSMPS 2050 2060 2070 2080 2090 2100 GSPCTALLNS IINNVNLYYV FSKIFGKSPV FFCQALKILC YGDDVLIVFS RDVQIDNLDL 2110 2120 2130 2140 2150 2160 IGQKIVDEFK KLGMTATSAD KNVPQLKPVS ELTFLKRSFN LVEDRIRPAI SEKTIWSLIA 2170 2180 2190 2200 2210 2220 WQRSNAEFEQ NLENAQWFAF MHGYEFYQKF YYFVQSCLEK EMIEYRLKSY DWWRMRFYDQ CFICDLS

References

[1]	"Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picornaviruses." Cohen J.I., Ticehurst J.R., Purcell R.H., Buckler-White A., Baroudy B.M. J. Virol. 61:50-59(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: HM175/wt.
[2]	"Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus." Cohen J.I., Rosenblum B., Ticehurst J.R., Daemer R.J., Feinstone S.M., Purcell R.H. Proc. Natl. Acad. Sci. U.S.A. 84:2497-2501(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: HM175/7 MK-5.
[3]	"Antigenic and genetic variation in cytopathic hepatitis A virus variants arising during persistent infection: evidence for genetic recombination." Lemon S.M., Murphy P.C., Shields P.A., Ping L.H., Feinstone S.M., Cromeans T., Jansen R.W. J. Virol. 65:2056-2065(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: HM175/18f, HM175/24a and HM175/43c.
[4]	"Sequence analysis of hepatitis A virus cDNA coding for capsid proteins and RNA polymerase." Baroudy B.M., Ticehurst J.R., Miele T.A., Maizel J.V. Jr., Purcell R.H., Feinstone S.M. Proc. Natl. Acad. Sci. U.S.A. 82:2143-2147(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-854 AND 1724-2227.
[5]	"Identification and site-directed mutagenesis of the primary (2A/2B) cleavage site of the hepatitis A virus polyprotein: functional impact on the infectivity of HAV RNA transcripts." Martin A., Escriou N., Chao S.-F., Girard M., Lemon S.M., Wychowski C. Virology 213:213-222(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 837-856, PROTEOLYTIC PROCESSING OF POLYPROTEIN, MUTAGENESIS OF GLN-836. Strain: HM175p35.
[6]	"Molecular cloning and characterization of hepatitis A virus cDNA." Ticehurst J.R., Racaniello V.R., Baroudy B.M., Baltimore D., Purcell R.H., Feinstone S.M. Proc. Natl. Acad. Sci. U.S.A. 80:5885-5889(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2090-2227.
[7]	"Proteolytic activity of hepatitis A virus 3C protein." Jia X.-Y., Ehrenfeld E., Summers D.F. J. Virol. 65:2595-2600(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[8]	"Hepatitis A virus polyprotein synthesis initiates from two alternative AUG codons." Tesar M., Harmon S.A., Summers D.F., Ehrenfeld E. Virology 186:609-618(1992) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF N-TERMINUS. Strain: HM175/7.
[9]	"Analysis of a potential myristoylation site in hepatitis A virus capsid protein VP4." Tesar M., Jia X.-Y., Summers D.F., Ehrenfeld E. Virology 194:616-626(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF PROTEIN VP4. Strain: HM175/7.
[10]	"Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region." Jia X.-Y., Summers D.F., Ehrenfeld E. Virology 193:515-519(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[11]	"Expression of hepatitis A virus precursor protein P3 in vivo and in vitro: polyprotein processing of the 3CD cleavage site." Tesar M., Pak I., Jia X.-Y., Richards O.C., Summers D.F., Ehrenfeld E. Virology 198:524-533(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[12]	"Proteinase 3C-mediated processing of VP1-2A of two hepatitis A virus strains: in vivo evidence for cleavage at amino acid position 273/274 of VP1." Probst C., Jecht M., Gauss-Mueller V. J. Virol. 71:3288-3292(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[13]	"Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC." Teterina N.L., Bienz K., Egger D., Gorbalenya A.E., Ehrenfeld E. Virology 237:66-77(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN 2C, FUNCTION OF PROTEIN 2BC. Strain: HM175/24a, HM175/wt and HM175p35.
[14]	"Membrane association and RNA binding of recombinant hepatitis A virus protein 2C." Kusov Y.Y., Probst C., Jecht M., Jost P.D., Gauss-Mueller V. Arch. Virol. 143:931-944(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION OF PROTEIN 2C, RNA-BINDING.
[15]	"Processing of proteinase precursors and their effect on hepatitis A virus particle formation." Probst C., Jecht M., Gauss-Mueller V. J. Virol. 72:8013-8020(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[16]	"The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor." Feigelstock D., Thompson P., Mattoo P., Zhang Y., Kaplan G.G. J. Virol. 72:6621-6628(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION OF CAPSID WITH HUMAN HAVCR1.
[17]	"Mapping of protein domains of hepatitis A virus 3AB essential for interaction with 3CD and viral RNA." Beneduce F., Ciervo A., Kusov Y.Y., Gauss-Mueller V., Morace G. Virology 264:410-421(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN 3AB, SUBUNIT, INTERACTION OF PROTEIN 3AB WITH PROTEIN 3CD. Strain: HM175/7.
[18]	"Hepatitis A virus capsid protein VP1 has a heterogeneous C terminus." Graff J., Richards O.C., Swiderek K.M., Davis M.T., Rusnak F., Harmon S.A., Jia X.-Y., Summers D.F., Ehrenfeld E. J. Virol. 73:6015-6023(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN. Strain: HM175p35 and HM175pE.
[19]	"Membrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC." Jecht M., Probst C., Gauss-Mueller V. Virology 252:218-227(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN 2B, FUNCTION OF PROTEIN 2BC.
[20]	"Intrinsic signals for the assembly of hepatitis A virus particles. Role of structural proteins VP4 and 2A." Probst C., Jecht M., Gauss-Mueller V. J. Biol. Chem. 274:4527-4531(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN VP1-2A, FUNCTION OF PROTEIN VP4.
[21]	"Analysis of deletion mutants indicates that the 2A polypeptide of hepatitis A virus participates in virion morphogenesis." Cohen L., Benichou D., Martin A. J. Virol. 76:7495-7505(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN 2A. Strain: HM175/18f.
[22]	"Homogenous hepatitis A virus particles. Proteolytic release of the assembly signal 2A from procapsids by factor Xa." Rachow A., Gauss-Mueller V., Probst C. J. Biol. Chem. 278:29744-29751(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF PROTEIN VP1-2A, SUBUNIT, MUTAGENESIS OF ARG-769.
[23]	"Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization." Peters H., Kusov Y.Y., Meyer S., Benie A.J., Baeuml E., Wolff M., Rademacher C., Peters T., Gauss-Mueller V. Biochem. J. 385:363-370(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-1691.
[24]	"Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor." Yang Y., Liang Y., Qu L., Chen Z., Yi M., Li K., Lemon S.M. Proc. Natl. Acad. Sci. U.S.A. 104:7253-7258(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF PROTEIN 3ABC, SUBCELLULAR LOCATION OF PROTEIN 3ABC, INTERACTION OF PROTEIN 3ABC WITH HUMAN MAVS. Strain: HM175/18f.
[25]	"RNA interaction and cleavage of poly(C)-binding protein 2 by hepatitis A virus protease." Zhang B., Seitz S., Kusov Y., Zell R., Gauss-Mueller V. Biochem. Biophys. Res. Commun. 364:725-730(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE OF HOST PCBP2 BY PICORNAIN 3C.
[26]	"Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases." Allaire M., Chernaia M.M., Malcolm B.A., James M.N. Nature 369:72-76(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
[27]	"The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition." Bergmann E.M., Mosimann S.C., Chernaia M.M., Malcolm B.A., James M.N.G. J. Virol. 71:2436-2448(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1520-1736.
[28]	"Crystal structure of an inhibitor complex of the 3C proteinase from hepatitis A virus (HAV) and implications for the polyprotein processing in HAV." Bergmann E.M., Cherney M.M., Mckendrick J., Frormann S., Luo C., Malcolm B.A., Vederas J.C., James M.N.G. Virology 265:153-163(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1520-1736 IN COMPLEX WITH THE INHIBITOR IODOACETYL-VALYL-PHENYLALANYL-AMIDE.
[29]	"An episulfide cation (thiiranium ring) trapped in the active site of HAV 3C proteinase inactivated by peptide-based ketone inhibitors." Yin J., Cherney M.M., Bergmann E.M., Zhang J., Huitema C., Pettersson H., Eltis L.D., Vederas J.C., James M.N.G. J. Mol. Biol. 361:673-686(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1520-1731 IN COMPLEX WITH PEPTIDE-BASED KETONE INHIBITORS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M14707 Genomic RNA. Translation: AAA45465.1.
M14707 Genomic RNA. Translation: AAA45466.1. Different initiation.
M16632 Genomic RNA. Translation: AAA45471.1.
M59808 Genomic RNA. Translation: AAA45467.1.
M59809 Genomic RNA. Translation: AAA45469.1.
M59810 Genomic RNA. Translation: AAA45468.1.
M14114 Genomic RNA. Translation: AAA45475.1.
M14115 Genomic RNA. Translation: AAA45476.1.
K00386 Genomic RNA. No translation available.

PIR

A03905.
GNNYHM. A25981.
GNNYMK. A94149.

RefSeq

NP_041007.1. NC_001489.1.
NP_041008.1. NC_001489.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HAV	X-ray	2.00	A/B	1520-1736	[»]
1QA7	X-ray	1.90	A/B/C/D	1520-1736	[»]
2H6M	X-ray	1.40	A	1520-1731	[»]
2H9H	X-ray	1.39	A	1520-1731	[»]
2HAL	X-ray	1.35	A	1520-1731	[»]

ProteinModelPortal

P08617.

SMR

P08617. Positions 1520-1735.

ModBase

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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.
IPR024354. Hepatitis_A_VP1-2A.
IPR000199. Peptidase_C3A/C3B_picornavir.
IPR001676. Picornavirus_capsid.
IPR001205. RNA-dir_pol_C.
IPR007094. RNA-dir_pol_PSvirus.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF12944. DUF3840. 1 hit.
PF00548. Peptidase_C3. 1 hit.
PF00680. RdRP_1. 1 hit.
PF00073. Rhv. 2 hits.
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...

Other

EvolutionaryTrace

P08617.

Entry information

Entry name

POLG_HAVHM

Accession

Primary (citable) accession number: P08617
Secondary accession number(s): P06443 , P26580, P26581, P26582, Q81082, Q81094

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	August 1, 1988
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program