ID   UL40_HCMVA              Reviewed;         221 AA.
AC   P16780; Q7M6P3;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   23-FEB-2022, entry version 57.
DE   RecName: Full=Protein UL40;
GN   Name=UL40;
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 [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   [2]
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   [3]
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   [4]
RP   REGION, AND FUNCTION.
RX   PubMed=10799855; DOI=10.4049/jimmunol.164.10.5019;
RA   Ulbrecht M., Martinozzi S., Grzeschik M., Hengel H., Ellwart J.W., Pla M.,
RA   Weiss E.H.;
RT   "The human cytomegalovirus UL40 gene product contains a ligand for HLA-E
RT   and prevents NK cell-mediated lysis.";
RL   J. Immunol. 164:5019-5022(2000).
RN   [5]
RP   FUNCTION.
RX   PubMed=10669413; DOI=10.1126/science.287.5455.1031;
RA   Tomasec P., Braud V.M., Rickards C., Powell M.B., McSharry B.P., Gadola S.,
RA   Cerundolo V., Borysiewicz L.K., McMichael A.J., Wilkinson G.W.;
RT   "Surface expression of HLA-E, an inhibitor of natural killer cells,
RT   enhanced by human cytomegalovirus gpUL40.";
RL   Science 287:1031-1031(2000).
RN   [6]
RP   FUNCTION.
RX   PubMed=22345649; DOI=10.4049/jimmunol.1102068;
RA   Prod'homme V., Tomasec P., Cunningham C., Lemberg M.K., Stanton R.J.,
RA   McSharry B.P., Wang E.C., Cuff S., Martoglio B., Davison A.J., Braud V.M.,
RA   Wilkinson G.W.;
RT   "Human cytomegalovirus UL40 signal peptide regulates cell surface
RT   expression of the NK cell ligands HLA-E and gpUL18.";
RL   J. Immunol. 188:2794-2804(2012).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 15-23.
RX   PubMed=16474394; DOI=10.1038/ni1312;
RA   Hoare H.L., Sullivan L.C., Pietra G., Clements C.S., Lee E.J., Ely L.K.,
RA   Beddoe T., Falco M., Kjer-Nielsen L., Reid H.H., McCluskey J., Moretta L.,
RA   Rossjohn J., Brooks A.G.;
RT   "Structural basis for a major histocompatibility complex class Ib-
RT   restricted T cell response.";
RL   Nat. Immunol. 7:256-264(2006).
CC   -!- FUNCTION: Plays a role in the protection against host NK-cell
CC       cytotoxicity by up-regulating the cell surface expression of HLA-E
CC       independent of TAP (HLA-E has an inhibitory effect on the cytotoxic
CC       activity of the NK cell). Promotes also cell surface expression of
CC       UL18, another viral protein involved in NK-cell evasion.
CC       {ECO:0000269|PubMed:10669413, ECO:0000269|PubMed:10799855,
CC       ECO:0000269|PubMed:22345649}.
CC   -!- SIMILARITY: Belongs to the HHV-5 UL40 protein family. {ECO:0000305}.
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DR   EMBL; X17403; CAA35399.1; -; Genomic_DNA.
DR   EMBL; BK000394; DAA00145.1; -; Genomic_DNA.
DR   PIR; S09803; S09803.
DR   PDB; 2ESV; X-ray; 2.60 A; P=15-23.
DR   PDB; 5W1V; X-ray; 3.31 A; C/H/M/R=15-23.
DR   PDBsum; 2ESV; -.
DR   PDBsum; 5W1V; -.
DR   SMR; P16780; -.
DR   EvolutionaryTrace; P16780; -.
DR   Proteomes; UP000008991; Genome.
DR   Proteomes; UP000008992; Genome.
DR   GO; GO:0039672; P:suppression by virus of host natural killer cell activation; IDA:UniProtKB.
DR   InterPro; IPR019624; Herpes_UL40.
DR   Pfam; PF10682; UL40; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Host-virus interaction;
KW   Modulation of host NK-cell activity by virus; Reference proteome;
KW   Viral immunoevasion.
FT   CHAIN           1..221
FT                   /note="Protein UL40"
FT                   /id="PRO_0000115322"
FT   REGION          15..23
FT                   /note="HLA-E-binding epitope"
SQ   SEQUENCE   221 AA;  24367 MW;  3A962EDE95B642A8 CRC64;
     MNKFSNTRIG FTCAVMAPRT LILTVGLLCM RIRSLLCSPA ETTVTTAAVT SAHGPLCPLV
     FQGWAYAVYH QGDMALMTLD VYCCRQTSNN TVVAFSHHPA DNTLLIEVGN NTRRHVDGIS
     CQDHFRAQHQ DCPAQTVHVR GVNESAFGLT HLQSCCLNEH SQLSERVAYH LKLRPATFGL
     ETWAMYTVGI LALGSFSSFY SQIARSLGVL PNDHHYALKK A