ORF3_HEVHY
ID ORF3_HEVHY Reviewed; 114 AA.
AC O90299; Q68984;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 23-FEB-2022, entry version 71.
DE RecName: Full=Protein ORF3;
DE Short=pORF3;
GN ORFNames=ORF3;
OS Hepatitis E virus genotype 1 (isolate Human/India/Hyderabad) (HEV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=512346;
OH NCBI_TaxID=69079; Bandicota bengalensis (lesser bandicoot rat).
OH NCBI_TaxID=9481; Callithrix.
OH NCBI_TaxID=9536; Cercopithecus hamlyni (Owl-faced monkey) (Hamlyn's monkey).
OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH NCBI_TaxID=9520; Saimiri (squirrel monkeys).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8567900; DOI=10.1128/jcm.33.10.2653-2659.1995;
RA Panda S.K., Nanda S.K., Zafrullah M., Ansari I.H., Ozdener M.H., Jameel S.;
RT "An Indian strain of hepatitis E virus (HEV): cloning, sequence, and
RT expression of structural region and antibody responses in sera from
RT individuals from an area of high-level HEV endemicity.";
RL J. Clin. Microbiol. 33:2653-2659(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Infectious clone pSGI-HEV;
RX PubMed=10666275; DOI=10.1128/jvi.74.5.2430-2437.2000;
RA Panda S.K., Ansari I.H., Durgapal H., Agrawal S., Jameel S.;
RT "The in vitro-synthesized RNA from a cDNA clone of hepatitis E virus is
RT infectious.";
RL J. Virol. 74:2430-2437(2000).
RN [3]
RP PHOSPHORYLATION AT SER-71, MUTAGENESIS OF SER-71, AND SUBCELLULAR LOCATION.
RX PubMed=9371561; DOI=10.1128/jvi.71.12.9045-9053.1997;
RA Zafrullah M., Ozdener M.H., Panda S.K., Jameel S.;
RT "The ORF3 protein of hepatitis E virus is a phosphoprotein that associates
RT with the cytoskeleton.";
RL J. Virol. 71:9045-9053(1997).
RN [4]
RP FUNCTION, AND INTERACTION WITH HUMAN SRC; HCK; FYN; PIK3R3 AND GRB2.
RX PubMed=11518702; DOI=10.1074/jbc.m101546200;
RA Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M.,
RA Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.;
RT "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and
RT activates MAPK.";
RL J. Biol. Chem. 276:42389-42400(2001).
RN [5]
RP SUBUNIT, AND REGION OF HOMODIMERIZATION.
RX PubMed=11160756; DOI=10.1128/jvi.75.5.2493-2498.2001;
RA Tyagi S., Jameel S., Lal S.K.;
RT "Self-association and mapping of the interaction domain of hepatitis E
RT virus ORF3 protein.";
RL J. Virol. 75:2493-2498(2001).
RN [6]
RP INTERACTION WITH THE CAPSID PROTEIN.
RX PubMed=11934888; DOI=10.1074/jbc.m200185200;
RA Tyagi S., Korkaya H., Zafrullah M., Jameel S., Lal S.K.;
RT "The phosphorylated form of the ORF3 protein of hepatitis E virus interacts
RT with its non-glycosylated form of the major capsid protein, ORF2.";
RL J. Biol. Chem. 277:22759-22767(2002).
RN [7]
RP FUNCTION, AND INTERACTION WITH HUMAN AMBP/ALPHA-1-MICROGLOBULIN.
RX PubMed=15037615; DOI=10.1074/jbc.m402017200;
RA Tyagi S., Surjit M., Roy A.K., Jameel S., Lal S.K.;
RT "The ORF3 protein of hepatitis E virus interacts with liver-specific
RT alpha1-microglobulin and its precursor alpha1-microglobulin/bikunin
RT precursor (AMBP) and expedites their export from the hepatocyte.";
RL J. Biol. Chem. 279:29308-29319(2004).
RN [8]
RP INTERACTION WITH HUMAN AMBP/BIKUNIN.
RX PubMed=16140784; DOI=10.1128/jvi.79.18.12081-12087.2005;
RA Tyagi S., Surjit M., Lal S.K.;
RT "The 41-amino-acid C-terminal region of the hepatitis E virus ORF3 protein
RT interacts with bikunin, a Kunitz-type serine protease inhibitor.";
RL J. Virol. 79:12081-12087(2005).
RN [9]
RP INTERACTION WITH HUMAN HPX.
RX PubMed=18211098; DOI=10.1021/bi7016552;
RA Ratra R., Kar-Roy A., Lal S.K.;
RT "The ORF3 protein of hepatitis E virus interacts with hemopexin by means of
RT its 26 amino acid N-terminal hydrophobic domain II.";
RL Biochemistry 47:1957-1969(2008).
CC -!- FUNCTION: Plays critical roles in the final steps of viral release by
CC interacting with host TSG101, a member of the vacuolar protein-sorting
CC pathway and using other cellular host proteins involved in vesicle
CC formation pathway. Acts also as a viroporin and forms ion conductive
CC pores allowing viral particle release. Impairs the generation of type I
CC interferon by down-regulating host TLR3 and TLR7 as well as their
CC downstream signaling pathways. {ECO:0000250|UniProtKB:Q81870,
CC ECO:0000269|PubMed:11518702, ECO:0000269|PubMed:15037615}.
CC -!- SUBUNIT: Forms homooligomers (By similarity). Interacts with host SRC,
CC HCK, FYN, PIK3R3 and GRB2 (via SH3 domain); binding does not activate
CC the kinases. Interacts with host AMBP/bikunin and AMBP/alpha-1-
CC microglobulin peptides. Interacts with host HPX/hemopexin. Interacts
CC (when phosphorylated) with capsid protein ORF2 (PubMed:11160756,
CC PubMed:11518702, PubMed:11934888, PubMed:15037615, PubMed:16140784,
CC PubMed:18211098). Interacts with host TSG101; this interaction plays a
CC role in viral release from the host cell (By similarity).
CC {ECO:0000250|UniProtKB:Q81870, ECO:0000269|PubMed:11160756,
CC ECO:0000269|PubMed:11518702, ECO:0000269|PubMed:11934888,
CC ECO:0000269|PubMed:15037615, ECO:0000269|PubMed:16140784,
CC ECO:0000269|PubMed:18211098}.
CC -!- INTERACTION:
CC O90299; Q9WC28: ORF1; NbExp=41; IntAct=EBI-11179411, EBI-11179420;
CC O90299; O90299: ORF3; NbExp=6; IntAct=EBI-11179411, EBI-11179411;
CC -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q81870}. Host cytoplasm
CC {ECO:0000269|PubMed:9371561}. Note=The N-terminal region seems to
CC associate with the cytoskeleton probably via one of its hydrophobic
CC regions. {ECO:0000269|PubMed:9371561}.
CC -!- SIMILARITY: Belongs to the hepevirus ORF3 protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA97365.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAC27935.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U22532; AAA97365.1; ALT_INIT; Genomic_RNA.
DR EMBL; AF076239; AAC27935.1; ALT_INIT; Genomic_RNA.
DR IntAct; O90299; 2.
DR iPTMnet; O90299; -.
DR Proteomes; UP000007244; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR003384; HEV_Orf2.
DR Pfam; PF02444; HEV_ORF1; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host endoplasmic reticulum; Host membrane;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Membrane; Phosphoprotein; Transmembrane; Transmembrane helix;
KW Viral immunoevasion.
FT CHAIN 1..114
FT /note="Protein ORF3"
FT /id="PRO_0000334539"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 6..24
FT /note="Hydrophobic"
FT REGION 28..68
FT /note="Interaction with host HPX"
FT REGION 33..53
FT /note="Hydrophobic"
FT REGION 48..72
FT /note="Interaction with the capsid protein"
FT REGION 72..114
FT /note="Homodimerization, and interaction with host
FT AMBP/bikunin"
FT REGION 85..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..104
FT /note="Interaction with host SRC, HCK, FYN, PIK3R3 and
FT GRB2"
FT /evidence="ECO:0000305"
FT MOD_RES 71
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:9371561"
FT MUTAGEN 71
FT /note="S->A: Complete loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:9371561"
SQ SEQUENCE 114 AA; 11806 MW; 94DE3D4161FAD67D CRC64;
MGSRPWALGL FCCCSSCFCL CCSRHRPVSR LAAVVGGAAA VPAVVSGVTG LILSPSQSPI
FIQPTPSPRM SPLRPGLDLV FANPSDHSAP LGATRPSAPP LPHVVDLPQL GPRR
