US28_HCMVA
ID US28_HCMVA Reviewed; 354 AA.
AC P69332; P09704; P32952; Q7M6H3;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=G-protein coupled receptor homolog US28;
DE AltName: Full=HHRF3;
GN Name=US28;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=Isolate clinical VHL/E;
RX PubMed=7540006; DOI=10.1006/bbrc.1995.1814;
RA Kuhn D.E., Beall C.J., Kolattukudy P.E.;
RT "The cytomegalovirus US28 protein binds multiple CC chemokines with high
RT affinity.";
RL Biochem. Biophys. Res. Commun. 211:325-330(1995).
RN [4]
RP CHARACTERIZATION.
RX PubMed=2158627; DOI=10.1038/344774a0;
RA Chee M.S., Satchwell S.C., Preddie E., Weston K.M., Barrell B.G.;
RT "Human cytomegalovirus encodes three G protein-coupled receptor
RT homologues.";
RL Nature 344:774-777(1990).
RN [5]
RP IDENTIFICATION OF C-TERMINAL FRAMESHIFT, AND FUNCTION.
RX PubMed=7961796; DOI=10.1016/s0021-9258(19)61936-8;
RA Gao J.-L., Murphy P.M.;
RT "Human cytomegalovirus open reading frame US28 encodes a functional beta
RT chemokine receptor.";
RL J. Biol. Chem. 269:28539-28542(1994).
RN [6]
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 [7]
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 [8]
RP FUNCTION.
RX PubMed=11050102; DOI=10.1074/jbc.m008965200;
RA Casarosa P., Bakker R.A., Verzijl D., Navis M., Timmerman H., Leurs R.,
RA Smit M.J.;
RT "Constitutive signaling of the human cytomegalovirus-encoded chemokine
RT receptor US28.";
RL J. Biol. Chem. 276:1133-1137(2001).
RN [9]
RP PHOSPHORYLATION.
RX PubMed=12244063; DOI=10.1074/jbc.m208214200;
RA Mokros T., Rehm A., Droese J., Oppermann M., Lipp M., Hopken U.E.;
RT "Surface expression and endocytosis of the human cytomegalovirus-encoded
RT chemokine receptor US28 is regulated by agonist-independent
RT phosphorylation.";
RL J. Biol. Chem. 277:45122-45128(2002).
RN [10]
RP INTERACTION WITH HOST GPRASP1.
RX PubMed=20102549; DOI=10.1111/j.1600-0854.2010.1045.x;
RA Tschische P., Moser E., Thompson D., Vischer H.F., Parzmair G.P.,
RA Pommer V., Platzer W., Schwarzbraun T., Schaider H., Smit M.J., Martini L.,
RA Whistler J.L., Waldhoer M.;
RT "The G-protein coupled receptor associated sorting protein GASP-1 regulates
RT the signalling and trafficking of the viral chemokine receptor US28.";
RL Traffic 11:660-674(2010).
RN [11] {ECO:0007744|PDB:4XT1, ECO:0007744|PDB:4XT3}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) IN COMPLEX WITH HOST CX3CL1,
RP INTERACTION WITH HOST CX3CL1, AND FUNCTION.
RX PubMed=25745166; DOI=10.1126/science.aaa5026;
RA Burg J.S., Ingram J.R., Venkatakrishnan A.J., Jude K.M., Dukkipati A.,
RA Feinberg E.N., Angelini A., Waghray D., Dror R.O., Ploegh H.L.,
RA Garcia K.C.;
RT "Structural basis for chemokine recognition and activation of a viral G
RT protein-coupled receptor.";
RL Science 347:1113-1117(2015).
RN [12] {ECO:0007744|PDB:7RKF, ECO:0007744|PDB:7RKM, ECO:0007744|PDB:7RKN}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS) IN COMPLEX WITH HOST
RP GNB1; GNA11; CX3CL1 AND GNG2, INTERACTION WITH HOST GNA11, STRUCTURE BY
RP ELECTRON MICROSCOPY (3.50 ANGSTROMS) IN COMPLEX WITH HOST GNB1; GNAI1;
RP CX3CL1 AND GNG2, AND FUNCTION.
RX PubMed=35061538; DOI=10.1126/sciadv.abl5442;
RA Tsutsumi N., Maeda S., Qu Q., Voegele M., Jude K.M., Suomivuori C.M.,
RA Panova O., Waghray D., Kato H.E., Velasco A., Dror R.O., Skiniotis G.,
RA Kobilka B.K., Garcia K.C.;
RT "Atypical structural snapshots of human cytomegalovirus GPCR interactions
RT with host G proteins.";
RL Sci. Adv. 8:eabl5442-eabl5442(2022).
CC -!- FUNCTION: Binds to a great number of different CC-chemokines including
CC CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-alpha as well as CX3CL1/Fractalkine
CC (PubMed:7961796, PubMed:25745166, PubMed:7540006). Transduces signals
CC resulting in the activation of MAP kinase signaling pathways and
CC augmentation of intracellular calcium ion levels, leading to
CC alterations in chemotactic behavior of vascular smooth muscle cells and
CC macrophages. The US28 receptor also exhibits high levels of agonist-
CC independent signaling activity and agonist-independent endocytosis
CC (PubMed:11050102, PubMed:25745166). Interacts with the host Gi complex
CC without activating it, thereby probably interfering with the chemokine-
CC Gi signaling (PubMed:35061538). May also function as a G protein sink
CC to sequester G protein from the cell surface via internalization
CC (PubMed:35061538). Interacts with endogenous Gaq/11 subunits and
CC thereby constitutively activates phospholipase C (PubMed:11050102).
CC {ECO:0000269|PubMed:11050102, ECO:0000269|PubMed:25745166,
CC ECO:0000269|PubMed:35061538, ECO:0000269|PubMed:7540006,
CC ECO:0000269|PubMed:7961796}.
CC -!- SUBUNIT: Interacts with host GPRASP1; this interaction targets US28 to
CC lysosomes for degradation (PubMed:20102549). Interacts with host
CC CX3CL1/Fractalkine (via N-terminus) (PubMed:25745166). Interacts with
CC host Gi alpha-1 subunit GNAI1; this interaction does not lead to the
CC catalytic activation of Gi complex (PubMed:35061538).
CC {ECO:0000269|PubMed:20102549, ECO:0000269|PubMed:25745166,
CC ECO:0000269|PubMed:35061538}.
CC -!- INTERACTION:
CC P69332; P78423: CX3CL1; Xeno; NbExp=4; IntAct=EBI-16147206, EBI-15188013;
CC -!- SUBCELLULAR LOCATION: Host cell membrane; Multi-pass membrane protein.
CC -!- PTM: Phosphorylated. High phosphorylation occurs concomitantly with
CC receptor endocytosis and correlate with low receptor presence at the
CC plasma membrane. {ECO:0000269|PubMed:12244063}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA28338.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA35260.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X04650; CAA28338.1; ALT_FRAME; Genomic_DNA.
DR EMBL; X17403; CAA35260.1; ALT_FRAME; Genomic_DNA.
DR EMBL; L20501; AAA98741.1; -; Genomic_DNA.
DR PIR; C27216; QQBED3.
DR PDB; 4XT1; X-ray; 2.89 A; A=1-354.
DR PDB; 4XT3; X-ray; 3.80 A; A=1-354.
DR PDB; 7RKF; EM; 4.00 A; F=1-354.
DR PDB; 7RKM; EM; 3.50 A; F=1-354.
DR PDB; 7RKN; EM; 3.60 A; F=1-354.
DR PDBsum; 4XT1; -.
DR PDBsum; 4XT3; -.
DR PDBsum; 7RKF; -.
DR PDBsum; 7RKM; -.
DR PDBsum; 7RKN; -.
DR SMR; P69332; -.
DR DIP; DIP-61489N; -.
DR IntAct; P69332; 1.
DR BindingDB; P69332; -.
DR ChEMBL; CHEMBL4259; -.
DR iPTMnet; P69332; -.
DR ABCD; P69332; 1 sequenced antibody.
DR Proteomes; UP000008991; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004950; F:chemokine receptor activity; IEA:InterPro.
DR GO; GO:0006935; P:chemotaxis; IEA:InterPro.
DR GO; GO:0044864; P:positive regulation by virus of host cell division; IDA:CACAO.
DR GO; GO:0039553; P:suppression by virus of host chemokine activity; IEA:UniProtKB-KW.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; G-protein coupled receptor; Glycoprotein; Host cell membrane;
KW Host membrane; Host-virus interaction;
KW Inhibition of host chemokines by virus; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Viral immunoevasion.
FT CHAIN 1..354
FT /note="G-protein coupled receptor homolog US28"
FT /id="PRO_0000070246"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..58
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..101
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..145
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 167..183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..354
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT VARIANT 18..19
FT /note="ED -> DE (in strain: Isolate clinical VHL/E)"
FT VARIANT 25
FT /note="F -> L (in strain: Isolate clinical VHL/E)"
FT VARIANT 267
FT /note="R -> K (in strain: Isolate clinical VHL/E)"
FT VARIANT 346
FT /note="V -> A (in strain: Isolate clinical VHL/E)"
FT HELIX 26..59
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 67..83
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 86..94
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 104..133
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 141..157
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:4XT1"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:4XT1"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:4XT1"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 184..196
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 198..215
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 223..255
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 263..280
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:4XT1"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:4XT1"
FT HELIX 296..308
FT /evidence="ECO:0007829|PDB:4XT1"
SQ SEQUENCE 354 AA; 41064 MW; 295A2F7C54DF7AAD CRC64;
MTPTTTTAEL TTEFDYDEDA TPCVFTDVLN QSKPVTLFLY GVVFLFGSIG NFLVIFTITW
RRRIQCSGDV YFINLAAADL LFVCTLPLWM QYLLDHNSLA SVPCTLLTAC FYVAMFASLC
FITEIALDRY YAIVYMRYRP VKQACLFSIF WWIFAVIIAI PHFMVVTKKD NQCMTDYDYL
EVSYPIILNV ELMLGAFVIP LSVISYCYYR ISRIVAVSQS RHKGRIVRVL IAVVLVFIIF
WLPYHLTLFV DTLKLLKWIS SSCEFERSLK RALILTESLA FCHCCLNPLL YVFVGTKFRQ
ELHCLLAEFR QRLFSRDVSW YHSMSFSRRS SPSRRETSSD TLSDEVCRVS QIIP