ORF3_HEVCH
ID ORF3_HEVCH Reviewed; 114 AA.
AC Q81870;
DT 30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 23-FEB-2022, entry version 72.
DE RecName: Full=Protein ORF3;
DE Short=pORF3;
GN ORFNames=ORF3;
OS Hepatitis E virus genotype 1 (isolate Human/China/HeBei/1987) (HEV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=652674;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8346669; DOI=10.1016/0168-1702(93)90024-h;
RA Bi S.L., Purdy M.A., McCaustland K.A., Margolis H.S., Bradley D.W.;
RT "The sequence of hepatitis E virus isolated directly from a single source
RT during an outbreak in China.";
RL Virus Res. 28:233-247(1993).
RN [2]
RP FUNCTION.
RX PubMed=19339479; DOI=10.1099/vir.0.010561-0;
RA Yamada K., Takahashi M., Hoshino Y., Takahashi H., Ichiyama K.,
RA Nagashima S., Tanaka T., Okamoto H.;
RT "ORF3 protein of hepatitis E virus is essential for virion release from
RT infected cells.";
RL J. Gen. Virol. 90:1880-1891(2009).
RN [3]
RP FUNCTION, INTERACTION WITH HOST TSG101, AND MOTIF.
RX PubMed=21068219; DOI=10.1099/vir.0.025791-0;
RA Nagashima S., Takahashi M., Jirintai S., Tanaka T., Yamada K.,
RA Nishizawa T., Okamoto H.;
RT "A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for
RT virion release from infected cells.";
RL J. Gen. Virol. 92:269-278(2011).
RN [4]
RP FUNCTION.
RX PubMed=27270888; DOI=10.1038/srep27597;
RA He M., Wang M., Huang Y., Peng W., Zheng Z., Xia N., Xu J., Tian D.;
RT "The ORF3 Protein of Genotype 1 Hepatitis E Virus Suppresses TLR3-induced
RT NF-kappaB Signaling via TRADD and RIP1.";
RL Sci. Rep. 6:27597-27597(2016).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=28096411; DOI=10.1073/pnas.1614955114;
RA Ding Q., Heller B., Capuccino J.M., Song B., Nimgaonkar I., Hrebikova G.,
RA Contreras J.E., Ploss A.;
RT "Hepatitis E virus ORF3 is a functional ion channel required for release of
RT infectious particles.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:1147-1152(2017).
RN [6]
RP FUNCTION.
RX PubMed=29872132; DOI=10.1038/s41598-018-26975-4;
RA Lei Q., Li L., Zhang S., Li T., Zhang X., Ding X., Qin B.;
RT "HEV ORF3 downregulates TLR7 to inhibit the generation of type I interferon
RT via impairment of multiple signaling pathways.";
RL Sci. Rep. 8:8585-8585(2018).
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 (PubMed:19339479, PubMed:21068219). Acts also as a
CC viroporin and forms ion conductive pores allowing viral particle
CC release (PubMed:28096411). Impairs the generation of type I interferon
CC by down-regulating host TLR3 and TLR7 as well as their downstream
CC signaling pathways (PubMed:27270888, PubMed:29872132).
CC {ECO:0000269|PubMed:19339479, ECO:0000269|PubMed:21068219,
CC ECO:0000269|PubMed:27270888, ECO:0000269|PubMed:28096411,
CC ECO:0000269|PubMed:29872132}.
CC -!- SUBUNIT: Forms homooligomers (PubMed:28096411). Interacts with host
CC SRC, HCK, FYN, PIK3R3 and GRB2 (via SH3 domain); binding does not
CC activate the kinases. Interacts with host AMBP/bikunin and AMBP/alpha-
CC 1-microglobulin peptides. Interacts with host HPX/hemopexin. Interacts
CC (when phosphorylated) with capsid protein ORF2 (By similarity).
CC Interacts with host TSG101; this interaction plays a role in viral
CC release from the host cell (PubMed:21068219).
CC {ECO:0000250|UniProtKB:O90299, ECO:0000269|PubMed:21068219,
CC ECO:0000269|PubMed:28096411}.
CC -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:28096411}. Host cytoplasm
CC {ECO:0000250|UniProtKB:O90299}. Note=The N-terminal region seems to
CC associate with the cytoskeleton probably via one of its hydrophobic
CC regions. {ECO:0000250|UniProtKB:O90299}.
CC -!- SIMILARITY: Belongs to the hepevirus ORF3 protein family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA03190.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M94177; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; L08816; AAA03190.1; ALT_INIT; Genomic_RNA.
DR PRIDE; Q81870; -.
DR SABIO-RK; Q81870; -.
DR Proteomes; UP000006705; Genome.
DR Proteomes; UP000102625; 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: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; Reference proteome; Transmembrane;
KW Transmembrane helix; Viral immunoevasion.
FT CHAIN 1..114
FT /note="Protein ORF3"
FT /id="PRO_0000402398"
FT TRANSMEM 33..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 6..22
FT /note="Hydrophobic"
FT /evidence="ECO:0000250"
FT REGION 28..68
FT /note="Interaction with host HPX"
FT /evidence="ECO:0000250"
FT REGION 33..53
FT /note="Hydrophobic"
FT /evidence="ECO:0000250"
FT REGION 48..72
FT /note="Interaction with the capsid protein"
FT /evidence="ECO:0000250"
FT REGION 72..114
FT /note="Homodimerization, and interaction with host
FT AMBP/bikunin"
FT /evidence="ECO:0000250"
FT REGION 91..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:0000250"
FT MOTIF 96..99
FT /note="PTAP/PSAP motif"
FT /evidence="ECO:0000269|PubMed:21068219"
FT MOD_RES 71
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q68984"
SQ SEQUENCE 114 AA; 11684 MW; DD03A7BC2D4687F6 CRC64;
MGSRPCALGL FCCCSSCFCL CCPRHRPVSR LAAAVGGAAA VPAVVSGVTG LILSPSQSPI
FIQPTPSPPM SPLRPGLDLV FANPPDHSAP LGVTRPSAPP LPHVVDLPQL GPRR
