ORF3_HEVME
ID ORF3_HEVME Reviewed; 114 AA.
AC Q03499;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 23-FEB-2022, entry version 73.
DE RecName: Full=Protein ORF3;
DE Short=pORF3;
GN ORFNames=ORF3;
OS Hepatitis E virus genotype 2 (isolate Human/Mexico) (HEV-2).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Hepelivirales; Hepeviridae; Orthohepevirus; Hepatitis E virus.
OX NCBI_TaxID=31768;
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=9031; Gallus gallus (Chicken).
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=1448913; DOI=10.1016/0042-6822(92)90230-m;
RA Huang C.C., Nguyen D., Fernandez J., Yun K.Y., Fry K.E., Bradley D.W.,
RA Tam A.W., Reyes G.R.;
RT "Molecular cloning and sequencing of the Mexico isolate of hepatitis E
RT virus (HEV).";
RL Virology 191:550-558(1992).
RN [2]
RP LACK OF 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 [3]
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).
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 (PubMed:16140784). Interacts with host
CC HPX/hemopexin. Interacts (when phosphorylated) with capsid protein
CC ORF2. Interacts with host TSG101; this interaction plays a role in
CC viral release from the host cell (By similarity).
CC {ECO:0000250|UniProtKB:O90299, ECO:0000250|UniProtKB:Q81870,
CC ECO:0000269|PubMed:16140784}.
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=AAA45731.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M74506; AAA45731.1; ALT_INIT; Genomic_RNA.
DR PIR; C44212; C44212.
DR MINT; Q03499; -.
DR Proteomes; UP000007245; 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; Transmembrane; Transmembrane helix;
KW Viral immunoevasion.
FT CHAIN 1..114
FT /note="Protein ORF3"
FT /id="PRO_0000100138"
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 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"
SQ SEQUENCE 114 AA; 11651 MW; C37ECCA9A5501367 CRC64;
MGSPPCALGL FCCCSSCFCL CCPRHRPVSR LAAVVGGAAA VPAVVSGVTG LILSPSQSPI
FIQPTPLPQT LPLRPGLDLA FANQPGHLAP LGEIRPSAPP LPPVADLPQP GLRR