ID   ORF3_HEVPA              Reviewed;         114 AA.
AC   P69617; P29325; Q77EC9;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   10-JUN-2008, sequence version 2.
DT   23-FEB-2022, entry version 47.
DE   RecName: Full=Protein ORF3;
DE            Short=pORF3;
GN   ORFNames=ORF3;
OS   Hepatitis E virus genotype 1 (isolate Human/Pakistan/Sar-55) (HEV-1).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC   Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX   NCBI_TaxID=33774;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1731327; DOI=10.1073/pnas.89.2.559;
RA   Tsarev S.A., Emerson S.U., Reyes G.R., Tsareva T.S., Legters L.J.,
RA   Malik I.A., Iqbal M., Purcell R.H.;
RT   "Characterization of a prototype strain of hepatitis E virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:559-563(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate pSK-HEV-2, and Isolate pSK-HEV-3;
RX   PubMed=11742081; DOI=10.1073/pnas.251555098;
RA   Emerson S.U., Zhang M., Meng X.J., Nguyen H., St Claire M.,
RA   Govindarajan S., Huang Y.K., Purcell R.H.;
RT   "Recombinant hepatitis E virus genomes infectious for primates: importance
RT   of capping and discovery of a cis-reactive element.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:15270-15275(2001).
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   -!- 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. Interacts with host
CC       TSG101; this interaction plays a role in viral release from the host
CC       cell (By similarity). {ECO:0000250|UniProtKB:O90299,
CC       ECO:0000250|UniProtKB:Q81870}.
CC   -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q81870}. 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=AAA45726.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAL50057.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAL50060.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; M80581; AAA45726.1; ALT_INIT; Genomic_RNA.
DR   EMBL; AF444002; AAL50057.1; ALT_INIT; Genomic_RNA.
DR   EMBL; AF444003; AAL50060.1; ALT_INIT; Genomic_RNA.
DR   Proteomes; UP000001322; Genome.
DR   Proteomes; UP000008498; Genome.
DR   Proteomes; UP000180763; 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   3: Inferred from homology;
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_0000100137"
FT   TRANSMEM        33..53
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          6..22
FT                   /note="Hydrophobic"
FT   REGION          28..68
FT                   /note="Interaction with host HPX"
FT                   /evidence="ECO:0000250"
FT   REGION          33..53
FT                   /note="Hydrophobic"
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   MOD_RES         71
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q68984"
SQ   SEQUENCE   114 AA;  11712 MW;  C5AC40F482A1D7F6 CRC64;
     MGSRPCALGL FCCCSSCFCL CCPRHRPVSR LAAVVGGAAA VPAVVSGVTG LILSPSQSPI
     FIQPTPSPPM SPLRPGLDLV FANPPDHSAP LGVTRPSAPP LPHVVDLPQL GPRR