ID   US03_HCMVT              Reviewed;         186 AA.
AC   B9VXD7;
DT   18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT   19-OCT-2011, sequence version 1.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Membrane glycoprotein US3;
DE   Flags: Precursor;
GN   Name=US3;
OS   Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX   NCBI_TaxID=10363;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Towne;
RX   PubMed=19553388; DOI=10.1099/vir.0.013250-0;
RA   Bradley A.J., Lurain N.S., Ghazal P., Trivedi U., Cunningham C.,
RA   Baluchova K., Gatherer D., Wilkinson G.W., Dargan D.J., Davison A.J.;
RT   "High-throughput sequence analysis of variants of human cytomegalovirus
RT   strains Towne and AD169.";
RL   J. Gen. Virol. 90:2375-2380(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA   Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA   Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA   Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT   "Genetic content of wild-type human cytomegalovirus.";
RL   J. Gen. Virol. 85:1301-1312(2004).
RN   [3]
RP   MUTAGENESIS OF SER-58; GLU-63 AND LYS-64.
RX   PubMed=12525649; DOI=10.1128/jvi.77.3.2147-2156.2003;
RA   Lee S., Park B., Ahn K.;
RT   "Determinant for endoplasmic reticulum retention in the luminal domain of
RT   the human cytomegalovirus US3 glycoprotein.";
RL   J. Virol. 77:2147-2156(2003).
CC   -!- FUNCTION: Retains, but does not degrade MHC class I heterodimers in the
CC       endoplasmic reticulum during the immediate-early period of virus
CC       infection, thereby impairing their transport and maturation. Forms a
CC       complex with beta-2-microglobulin-associated class I heavy chains,
CC       which accumulate in the ER. In consequence, infected cells are masked
CC       for immune recognition by cytotoxic T-lymphocytes.
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane; Single-pass
CC       type I membrane protein.
CC   -!- DEVELOPMENTAL STAGE: Expressed at immediate-early period of virus
CC       infection and at reduced levels at early-late times.
CC   -!- PTM: The signal sequence is not cleaved. {ECO:0000250}.
CC   -!- PTM: N-glycosylated; mostly exists in a high-mannose form.
CC   -!- SIMILARITY: Belongs to the cytomegalovirus US2 family. {ECO:0000305}.
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DR   EMBL; FJ616285; ACM48091.1; -; Genomic_DNA.
DR   SMR; B9VXD7; -.
DR   Proteomes; UP000006907; 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:0005537; F:mannose binding; IEA:UniProtKB-KW.
DR   InterPro; IPR009237; Herpes_US2/US3.
DR   InterPro; IPR014756; Ig_E-set.
DR   Pfam; PF05963; Cytomega_US3; 1.
DR   SUPFAM; SSF81296; SSF81296; 1.
PE   1: Evidence at protein level;
KW   Disulfide bond; Early protein; Glycoprotein; Host endoplasmic reticulum;
KW   Host membrane; Host-virus interaction; Immunoglobulin domain; Lectin;
KW   Mannose-binding; Membrane; Signal; Transmembrane; Transmembrane helix;
KW   Viral immunoevasion.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..186
FT                   /note="Membrane glycoprotein US3"
FT                   /id="PRO_0000416722"
FT   TOPO_DOM        21..160
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        161..181
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        182..186
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        60
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        44..129
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         58
FT                   /note="S->A: Loss of endoplasmic reticulum retention."
FT                   /evidence="ECO:0000269|PubMed:12525649"
FT   MUTAGEN         63
FT                   /note="E->A: Loss of endoplasmic reticulum retention."
FT                   /evidence="ECO:0000269|PubMed:12525649"
FT   MUTAGEN         64
FT                   /note="K->A: Loss of endoplasmic reticulum retention."
FT                   /evidence="ECO:0000269|PubMed:12525649"
SQ   SEQUENCE   186 AA;  21515 MW;  CB68FE1E6D6B0DE8 CRC64;
     MKPVLVLAIL AVLFLRLADS VPRPLDVVVS EIRSAHFRVE ENQCWFHMGM LHYKGRMSGN
     FTEKHFVSVG IVSQSYMDRL QVSGEQYHHD ERGAYFEWNI GGHPVPHTVD MVDITLSTRW
     GDPKKYAACV PQVRMDYSSQ TINWYLQRSI RDDNWGLLFR TLLVYLFSLV VLVLLTVGVS
     ARLRFI