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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};
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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
 
 
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