US02_HCMVA
ID US02_HCMVA Reviewed; 199 AA.
AC P09713; Q7M6I0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Unique short US2 glycoprotein;
DE AltName: Full=Protein HQLF2;
DE AltName: Full=gpUS2;
GN Name=US2;
OS Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10360;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3031311; DOI=10.1016/0022-2836(86)90359-1;
RA Weston K.M., Barrell B.G.;
RT "Sequence of the short unique region, short repeats, and part of the long
RT repeats of human cytomegalovirus.";
RL J. Mol. Biol. 192:177-208(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT "Analysis of the protein-coding content of the sequence of human
RT cytomegalovirus strain AD169.";
RL Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN [3]
RP GENOME REANNOTATION.
RX PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RT "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT cytomegalovirus genome.";
RL J. Gen. Virol. 84:17-28(2003).
RN [4]
RP ERRATUM OF PUBMED:12533697.
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RL J. Gen. Virol. 84:1053-1053(2003).
RN [5]
RP FUNCTION.
RX PubMed=8945469; DOI=10.1038/384432a0;
RA Wiertz E.J.H.J., Tortorella D., Bogyo M., Yu J., Mothes W., Jones T.R.,
RA Rapoport T.A., Ploegh H.L.;
RT "Sec61-mediated transfer of a membrane protein from the endoplasmic
RT reticulum to the proteasome for destruction.";
RL Nature 384:432-438(1996).
RN [6]
RP BINDING TO CLASS I MOLECULES.
RX PubMed=11333901; DOI=10.1128/jvi.75.11.5197-5204.2001;
RA Gewurz B.E., Wang E.W., Tortorella D., Schust D.J., Ploegh H.L.;
RT "Human cytomegalovirus US2 endoplasmic reticulum-lumenal domain dictates
RT association with major histocompatibility complex class I in a locus-
RT specific manner.";
RL J. Virol. 75:5197-5204(2001).
RN [7]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-68, AND NON-CLEAVABLE SIGNAL
RP PEPTIDE.
RX PubMed=11790769; DOI=10.1074/jbc.m107904200;
RA Gewurz B.E., Ploegh H.L., Tortorella D.;
RT "US2, a human cytomegalovirus-encoded type I membrane protein, contains a
RT non-cleavable amino-terminal signal peptide.";
RL J. Biol. Chem. 277:11306-11313(2002).
RN [8]
RP FUNCTION.
RX PubMed=16098592; DOI=10.1016/j.molimm.2005.07.005;
RA Barel M.T., Hassink G.C., van Voorden S., Wiertz E.J.;
RT "Human cytomegalovirus-encoded US2 and US11 target unassembled MHC class I
RT heavy chains for degradation.";
RL Mol. Immunol. 43:1258-1266(2006).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST TRAM1.
RX PubMed=19121997; DOI=10.1074/jbc.m807568200;
RA Oresic K., Ng C.L., Tortorella D.;
RT "TRAM1 participates in human cytomegalovirus US2- and US11-mediated
RT dislocation of an endoplasmic reticulum membrane glycoprotein.";
RL J. Biol. Chem. 284:5905-5914(2009).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 43-137 OF COMPLEX WITH HLA-A2/TAX,
RP AND DISULFIDE BONDS.
RX PubMed=11391001; DOI=10.1073/pnas.121172898;
RA Gewurz B.E., Gaudet R., Tortorella D., Wang E.W., Ploegh H.L., Wiley D.C.;
RT "Antigen presentation subverted: structure of the human cytomegalovirus
RT protein US2 bound to the class I molecule HLA-A2.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:6794-6799(2001).
CC -!- FUNCTION: Participates in the inhibition of the host immune response.
CC Early protein that redirects newly synthesized major histocompatibility
CC complex (MHC) class I heavy chains via the SEC61 translocon to the
CC cytosol where they undergo proteasome-dependent destruction
CC (PubMed:19121997). In consequence, infected cells are masked for immune
CC recognition by cytotoxic T lymphocytes. Seems so far to be specific for
CC HLA-A, HLA-B, and HFE loci products. Does not interact with HLA-DR or
CC HLA-DM. {ECO:0000269|PubMed:16098592, ECO:0000269|PubMed:19121997,
CC ECO:0000269|PubMed:8945469}.
CC -!- SUBUNIT: Monomer (Probable). Interacts with host TRAM1
CC (PubMed:19121997). {ECO:0000269|PubMed:19121997, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11790769}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:11790769}.
CC -!- DEVELOPMENTAL STAGE: Expressed at early period of virus infection.
CC -!- DOMAIN: The lumenal domain allows tight interaction with class I
CC molecules encoded by the HLA-A locus.
CC -!- PTM: The signal sequence is not cleaved.
CC -!- SIMILARITY: Belongs to the cytomegalovirus US2 family. {ECO:0000305}.
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DR EMBL; X17403; CAA35313.1; -; Genomic_DNA.
DR EMBL; X04650; CAB37096.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00208.1; -; Genomic_DNA.
DR PIR; E26078; QQBEC5.
DR PDB; 1IM3; X-ray; 2.20 A; D/H/L/P=43-137.
DR PDBsum; 1IM3; -.
DR SMR; P09713; -.
DR iPTMnet; P09713; -.
DR EvolutionaryTrace; P09713; -.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; 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 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 3D-structure; Disulfide bond; Early protein; Glycoprotein;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Immunoglobulin domain; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Viral immunoevasion.
FT CHAIN 1..199
FT /note="Unique short US2 glycoprotein"
FT /id="PRO_0000223275"
FT SIGNAL 1..?
FT /note="Not cleaved"
FT TOPO_DOM 1..161
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..199
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..137
FT /note="Ig-like H-type"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000305|PubMed:11790769"
FT DISULFID 52..133
FT /evidence="ECO:0000269|PubMed:11391001"
FT STRAND 45..54
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 56..67
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 72..82
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1IM3"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:1IM3"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 101..110
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:1IM3"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:1IM3"
SQ SEQUENCE 199 AA; 23111 MW; 4DD2DF3D692393F3 CRC64;
MNNLWKAWVG LWTSMGPLIR LPDGITKAGE DALRPWKSTA KHPWFQIEDN RCYIDNGKLF
ARGSIVGNMS RFVFDPKADY GGVGENLYVH ADDVEFVPGE SLKWNVRNLD VMPIFETLAL
RLVLQGDVIW LRCVPELRVD YTSSAYMWNM QYGMVRKSYT HVAWTIVFYS INITLLVLFI
VYVTVDCNLS MMWMRFFVC
