UL141_HCMVM
ID UL141_HCMVM Reviewed; 338 AA.
AC Q6RJQ3; Q56JA4; Q6E2A5; Q6E2A6; Q6E2A7; Q6E2B3; Q6E2B4; Q6RJP5; Q6RJP6;
AC Q6RJP7; Q6RJP9; Q6RJQ0; Q6RJQ1; Q6SWK7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 23-FEB-2022, entry version 80.
DE RecName: Full=Protein UL141;
DE Flags: Precursor;
GN Name=UL141;
OS Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=295027;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate 10J, Isolate 12M, Isolate 13J, Isolate 14J, Isolate 16m,
RC Isolate 18M, Isolate 1M, Isolate 20M, Isolate 27C, Isolate 29C, Isolate 2J,
RC Isolate 32C, Isolate 33J, Isolate 39J, Isolate 51C, Isolate 63J,
RC Isolate 84, Isolate 8J, and Isolate 9J;
RX PubMed=16195788; DOI=10.1007/s00705-005-0638-2;
RA Ma Y.P., Ruan Q., He R., Qi Y., Sun Z.R., Ji Y.H., Huang Y.J., Liu Q.,
RA Chen S.R., Wang J.D.;
RT "Sequence variability of the human cytomegalovirus UL141 open reading frame
RT in clinical strains.";
RL Arch. Virol. 151:827-835(2006).
RN [3]
RP INTERACTION WITH HUMAN PVR.
RX PubMed=15640804; DOI=10.1038/ni1156;
RA Tomasec P., Wang E.C., Davison A.J., Vojtesek B., Armstrong M., Griffin C.,
RA McSharry B.P., Morris R.J., Llewellyn-Lacey S., Rickards C., Nomoto A.,
RA Sinzger C., Wilkinson G.W.;
RT "Downregulation of natural killer cell-activating ligand CD155 by human
RT cytomegalovirus UL141.";
RL Nat. Immunol. 6:181-188(2005).
RN [4]
RP FUNCTION.
RX PubMed=20410314; DOI=10.1099/vir.0.021931-0;
RA Prod'homme V., Sugrue D.M., Stanton R.J., Nomoto A., Davies J.,
RA Rickards C.R., Cochrane D., Moore M., Wilkinson G.W., Tomasec P.;
RT "Human cytomegalovirus UL141 promotes efficient downregulation of the
RT natural killer cell activating ligand CD112.";
RL J. Gen. Virol. 91:2034-2039(2010).
RN [5]
RP FUNCTION, AND INTERACTION WITH HUMAN TNFRSF10A AND TNFRSF10B.
RX PubMed=23498957; DOI=10.1016/j.chom.2013.02.003;
RA Smith W., Tomasec P., Aicheler R., Loewendorf A., Nemcovicova I.,
RA Wang E.C., Stanton R.J., Macauley M., Norris P., Willen L., Ruckova E.,
RA Nomoto A., Schneider P., Hahn G., Zajonc D.M., Ware C.F., Wilkinson G.W.,
RA Benedict C.A.;
RT "Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors
RT to thwart host innate antiviral defenses.";
RL Cell Host Microbe 13:324-335(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 32-246, INTERACTION WITH HOST
RP TNFRSF10B, AND GLYCOSYLATION AT ASN-117; ASN-132 AND ASN-147.
RX PubMed=23555243; DOI=10.1371/journal.ppat.1003224;
RA Nemcovicova I., Benedict C.A., Zajonc D.M.;
RT "Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals
RT novel, non-canonical death receptor interactions.";
RL PLoS Pathog. 9:E1003224-E1003224(2013).
CC -!- FUNCTION: Evasion of NK cell killing. Blocks surface expression of PVR
CC which is a ligand for NK cell-activating receptors. Binds human PVR in
CC the endoplasmic reticulum and prevents its maturation and transport to
CC the cell surface. Targets also the natural killer cell activating
CC ligand NECTIN2 for proteasome-mediated degradation. Additionally
CC promotes intracellular retention of TNFRSF10A/TRAIL-R1 and
CC TNFRSF10B/TRAIL-R2 and thus down-regulates their cell surface
CC expression. {ECO:0000269|PubMed:20410314, ECO:0000269|PubMed:23498957}.
CC -!- SUBUNIT: Interacts with human PVR. Interacts with human TNFRSF10A and
CC TNFRSF10B. Forms a homodimer that engages two TNFRSF10B monomers.
CC {ECO:0000269|PubMed:15640804, ECO:0000269|PubMed:23498957,
CC ECO:0000269|PubMed:23555243}.
CC -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- INDUCTION: Early-late protein.
CC -!- CAUTION: The UL/b' region coding for this gene is deleted in some HHV-5
CC laboratory strains, like strains AD169 or Towne. {ECO:0000305}.
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DR EMBL; JX512197; AAR31489.1; -; Genomic_DNA.
DR EMBL; AY446894; AAR31679.1; -; Genomic_DNA.
DR EMBL; AY600463; AAT68302.1; -; Genomic_DNA.
DR EMBL; AY496555; AAR92108.1; -; Genomic_DNA.
DR EMBL; AY496547; AAR92100.1; -; Genomic_DNA.
DR EMBL; AY600467; AAT68306.1; -; Genomic_DNA.
DR EMBL; AY496549; AAR92102.1; -; Genomic_DNA.
DR EMBL; AY496550; AAR92103.1; -; Genomic_DNA.
DR EMBL; AY941105; AAX57274.1; -; Genomic_DNA.
DR EMBL; AY496551; AAR92104.1; -; Genomic_DNA.
DR EMBL; AY600465; AAT68304.1; -; Genomic_DNA.
DR EMBL; AY600466; AAT68305.1; -; Genomic_DNA.
DR EMBL; AY600464; AAT68303.1; -; Genomic_DNA.
DR EMBL; AY600462; AAT68301.1; -; Genomic_DNA.
DR EMBL; AY496552; AAR92105.1; -; Genomic_DNA.
DR EMBL; AY496548; AAR92101.1; -; Genomic_DNA.
DR EMBL; AY600468; AAT68307.1; -; Genomic_DNA.
DR EMBL; AY600461; AAT68300.1; -; Genomic_DNA.
DR EMBL; AY600459; AAT68298.1; -; Genomic_DNA.
DR EMBL; AY941104; AAX57273.1; -; Genomic_DNA.
DR EMBL; AY496554; AAR92107.1; -; Genomic_DNA.
DR EMBL; AY600460; AAT68299.1; -; Genomic_DNA.
DR EMBL; AY496553; AAR92106.1; -; Genomic_DNA.
DR RefSeq; YP_081575.1; NC_006273.2.
DR PDB; 4I9X; X-ray; 2.10 A; A/B=32-246.
DR PDB; 4JM0; X-ray; 3.25 A; A/B=30-279.
DR PDBsum; 4I9X; -.
DR PDBsum; 4JM0; -.
DR SMR; Q6RJQ3; -.
DR iPTMnet; Q6RJQ3; -.
DR PRIDE; Q6RJQ3; -.
DR DNASU; 3077418; -.
DR GeneID; 3077418; -.
DR KEGG; vg:3077418; -.
DR Proteomes; UP000000938; Genome.
DR Proteomes; UP000169440; 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:0039671; P:evasion by virus of host natural killer cell activity; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.3790; -; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR031918; UL141.
DR InterPro; IPR038504; UL141-like_sf.
DR Pfam; PF16758; UL141; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Host endoplasmic reticulum; Host membrane;
KW Host-virus interaction; Membrane;
KW Modulation of host NK-cell activity by virus; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Viral immunoevasion.
FT SIGNAL 1..36
FT CHAIN 37..338
FT /note="Protein UL141"
FT /id="PRO_0000253802"
FT TOPO_DOM 37..278
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 300..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:23555243"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:23555243"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:23555243"
FT VARIANT 8
FT /note="R -> Q (in strain: Isolate 1M)"
FT VARIANT 16
FT /note="V -> T (in strain: Isolate 45J)"
FT VARIANT 24
FT /note="L -> F (in strain: Isolate 1M, Isolate 10J, Isolate
FT 2J, Isolate 29C, Isolate 27C, Isolate 18M, Isolate 33J,
FT Isolate 14, Isolate 32C, Isolate 39J, Isolate 63J, Isolate
FT 25J and Isolate 9J)"
FT VARIANT 25
FT /note="E -> K (in strain: Isolate 10J, Isolate 2J, Isolate
FT 29C, Isolate 27C, Isolate 18M, Isolate 33J, Isolate 14,
FT Isolate 32C, Isolate 39J and Isolate 63J)"
FT VARIANT 26
FT /note="Y -> H (in strain: Isolate 8J, Isolate 16m and
FT Isolate 63J)"
FT VARIANT 28
FT /note="S -> F (in strain: Isolate 84)"
FT VARIANT 30
FT /note="S -> L (in strain: Isolate 8J and Isolate 16m)"
FT VARIANT 35
FT /note="T -> I (in strain: Isolate 45J)"
FT VARIANT 135
FT /note="T -> M (in strain: Isolate 2J, Isolate 10J, Isolate
FT 29C, Isolate 27C, Isolate 18M, Isolate 33J, Isolate 45J and
FT Isolate 14)"
FT VARIANT 139
FT /note="G -> S (in strain: Isolate 10J)"
FT VARIANT 202
FT /note="M -> T (in strain: Isolate 2J, Isolate 10J, Isolate
FT 25J, Isolate 39J, Isolate 45J, Isolate 29C, Isolate 27C,
FT Isolate 18M, Isolate 33 and Isolate 14)"
FT VARIANT 218
FT /note="A -> V (in strain: Isolate 2J, Isolate 10J, Isolate
FT 25J, Isolate 29C, Isolate 27C, Isolate 39J, Isolate 18M,
FT Isolate 33J and Isolate 14)"
FT VARIANT 306
FT /note="R -> H"
FT VARIANT 323
FT /note="R -> C (in strain: Isolate 13J and Isolate 51C)"
FT VARIANT 334
FT /note="K -> R (in strain: Isolate 2J, Isolate 10J, Isolate
FT 45J, Isolate 29C, Isolate 27C, Isolate 18M, Isolate 33J and
FT Isolate 14)"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:4I9X"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 75..86
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:4I9X"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:4I9X"
FT TURN 106..110
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 122..132
FT /evidence="ECO:0007829|PDB:4I9X"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 148..165
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:4I9X"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:4I9X"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:4I9X"
FT HELIX 235..238
FT /evidence="ECO:0007829|PDB:4I9X"
SQ SEQUENCE 338 AA; 38918 MW; D3E1152EB676F6CE CRC64;
MCRRESLRTL PWLFWVLLSC PRLLEYSSSS FPFATADIAE KMWAENYETT SPAPVLVAEG
EQVTIPCTVM THSWPMVSIR ARFCRSHDGS DELILDAVKG HRLMNGLQYR LPYATWNFSQ
LHLGQIFSLT FNVSTDTAGM YECVLRNYSH GLIMQRFVIL TQLETLSRPD EPCCTPALGR
YSLGDQIWSP TPWRLRNHDC GMYRGFQRNY FYIGRADAED CWKPACPDEE PDRCWTVIQR
YRLPGDCYRS QPHPPKFLPV TPAPPADIDT GMSPWATRGI AAFLGFWSIF TVCFLCYLCY
LQCCGRWCPT PGRGRRGGEG YRRLPTYDSY PGVKKMKR
