US28_HCMVT
ID US28_HCMVT Reviewed; 354 AA.
AC P69333; 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 69.
DE RecName: Full=G-protein coupled receptor homolog US28;
DE AltName: Full=HHRF3;
GN Name=US28;
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 [GENOMIC DNA].
RX PubMed=7679328; DOI=10.1016/0092-8674(93)90118-a;
RA Neote K., Digregorio D., Mak J.Y., Horuk R., Schall T.J.;
RT "Molecular cloning, functional expression, and signaling characteristics of
RT a C-C chemokine receptor.";
RL Cell 72:415-425(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12599055; DOI=10.1086/367900;
RA Rasmussen L., Geissler A., Winters M.;
RT "Inter- and intragenic variations complicate the molecular epidemiology of
RT human cytomegalovirus.";
RL J. Infect. Dis. 187:809-819(2003).
RN [3] {ECO:0007744|PDB:5WB1, ECO:0007744|PDB:5WB2}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 1-310 IN COMPLEX WITH HOST
RP CX3CL1, INTERACTION WITH HOST CX3CL1, AND FUNCTION.
RX PubMed=29882741; DOI=10.7554/elife.35850;
RA Miles T.F., Spiess K., Jude K.M., Tsutsumi N., Burg J.S., Ingram J.R.,
RA Waghray D., Hjorto G.M., Larsen O., Ploegh H.L., Rosenkilde M.M.,
RA Garcia K.C.;
RT "Viral GPCR US28 can signal in response to chemokine agonists of nearly
RT unlimited structural degeneracy.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Receptor for a C-C type chemokine. Binds to a great number of
CC different CC-chemokines including CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-
CC alpha as well as CX3CL1/Fractalkine (PubMed:29882741). Transduces
CC signals resulting in the activation of MAP kinase signaling pathways
CC and 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 Interacts with the host Gi complex without activating it, thereby
CC probably interfering with the chemokine-Gi signaling. May also function
CC as a G protein sink to sequester G protein from the cell surface via
CC internalization. Interacts with endogenous Gaq/11 subunits and thereby
CC constitutively activates phospholipase C (By similarity).
CC {ECO:0000250|UniProtKB:P69332, ECO:0000269|PubMed:29882741}.
CC -!- SUBUNIT: Interacts with host GPRASP1; this interaction targets US28 to
CC lysosomes for degradation (By similarity). Interacts with host
CC CX3CL1/Fractalkine (via N-terminus) (PubMed:29882741).
CC {ECO:0000250|UniProtKB:P69332, ECO:0000269|PubMed:29882741}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane
CC {ECO:0000250|UniProtKB:P69332}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P69332}.
CC -!- PTM: Phosphorylated. High phosphorylation occurs concomitantly with
CC receptor endocytosis and correlate with low receptor presence at the
CC plasma membrane. {ECO:0000250|UniProtKB:P69332}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AY174281; AAO22971.1; -; Genomic_DNA.
DR PDB; 5WB1; X-ray; 3.51 A; A=1-310.
DR PDB; 5WB2; X-ray; 3.50 A; A=1-310.
DR PDBsum; 5WB1; -.
DR PDBsum; 5WB2; -.
DR SMR; P69333; -.
DR ABCD; P69333; 1 sequenced antibody.
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: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; Transducer;
KW Transmembrane; Transmembrane helix; Viral immunoevasion.
FT CHAIN 1..354
FT /note="G-protein coupled receptor homolog US28"
FT /id="PRO_0000070247"
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 HELIX 26..59
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 67..83
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 86..94
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 101..133
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 141..163
FT /evidence="ECO:0007829|PDB:5WB2"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:5WB2"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 184..196
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 198..215
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 223..255
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 263..280
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:5WB2"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:5WB2"
FT HELIX 296..306
FT /evidence="ECO:0007829|PDB:5WB2"
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
