ID GPR84_HUMAN Reviewed; 396 AA.
AC Q9NQS5; B6V9G7;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=G-protein coupled receptor 84;
DE AltName: Full=Inflammation-related G-protein coupled receptor EX33;
GN Name=GPR84; Synonyms=EX33;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11404393;
RA Yousefi S., Cooper P.R., Potter S.L., Mueck B., Jarai G.;
RT "Cloning and expression analysis of a novel G-protein-coupled receptor
RT selectively expressed on granulocytes.";
RL J. Leukoc. Biol. 69:1045-1052(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11273702; DOI=10.1006/jmbi.2001.4520;
RA Wittenberger T., Schaller H.C., Hellebrand S.;
RT "An expressed sequence tag (EST) data mining strategy succeeding in the
RT discovery of new G-protein coupled receptors.";
RL J. Mol. Biol. 307:799-813(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for Homo sapiens G protein-coupled receptor 84
RT (GPR84).";
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12044878; DOI=10.1016/s0014-5793(02)02775-8;
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RT "Identification of G protein-coupled receptor genes from the human genome
RT sequence.";
RL FEBS Lett. 520:97-101(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=16966319; DOI=10.1074/jbc.m608019200;
RA Wang J., Wu X., Simonavicius N., Tian H., Ling L.;
RT "Medium-chain fatty acids as ligands for orphan G protein-coupled receptor
RT GPR84.";
RL J. Biol. Chem. 281:34457-34464(2006).
RN [8]
RP VARIANT ARG-367.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [9]
RP FUNCTION.
RX PubMed=33789297; DOI=10.1159/000514887;
RA Maartensson J., Sundqvist M., Manandhar A., Ieremias L., Zhang L.,
RA Ulven T., Xie X., Bjoerkman L., Forsman H.;
RT "The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated
RT Neutrophil NADPH Oxidase Activity.";
RL J. Innate Immun. 13:242-256(2021).
RN [10]
RP FUNCTION, PHOSPHORYLATION AT SER-221; SER-224; THR-263 AND THR-264,
RP INTERACTION WITH ARRB2 AND ARR3, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-263 AND THR-264.
RX PubMed=35427647; DOI=10.1016/j.jbc.2022.101932;
RA Marsango S., Ward R.J., Jenkins L., Butcher A.J., Al Mahmud Z., Dwomoh L.,
RA Nagel F., Schulz S., Tikhonova I.G., Tobin A.B., Milligan G.;
RT "Selective phosphorylation of threonine residues defines GPR84-arrestin
RT interactions of biased ligands.";
RL J. Biol. Chem. 298:101932-101932(2022).
CC -!- FUNCTION: G protein-coupled receptor that responds endogenously to
CC dietary fatty acids or nutrient, specifically medium-chain free fatty
CC acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0),
CC undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent
CC agonists (PubMed:16966319). In immune cells, functions as a pro-
CC inflammatory receptor via 6-OAU and promotes the expression of pro-
CC inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as
CC stimulating chemotactic responses through activation of signaling
CC mediators AKT, ERK and NF-kappa-B (By similarity). In addition,
CC triggers increased bacterial adhesion and phagocytosis in macrophages
CC and regulates pro-inflammatory function via enhancing NLRP3
CC inflammasome activation (By similarity). Plays also an important role
CC in inflammation by modulating neutrophil functions (By similarity).
CC Mechanistically, promotes neutrophil chemotaxis, reactive oxygen
CC species (ROS) production and degranulation via LYN-AKT/ERK pathway (By
CC similarity). To regulate ROS, communicates with the two formyl peptide
CC receptors FPR2 and FPR1 to control the NADPH oxidase activity in
CC neutrophils (PubMed:33789297). {ECO:0000250|UniProtKB:Q8CIM5,
CC ECO:0000269|PubMed:16966319, ECO:0000269|PubMed:33789297}.
CC -!- SUBUNIT: Interacts with ARRB2 and ARR3. {ECO:0000269|PubMed:35427647}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35427647};
CC Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in hematopoietic tissues.
CC High levels detected in the bone marrow and lower levels in the
CC peripheral leukocytes and lung. Also expressed in brain, heart, muscle,
CC colon, thymus, splen, kidney, liver, placenta and intestine. Within the
CC leukocyte population expression is higher in neutrophils and
CC eosinophils relative to T- or B-lymphocytes.
CC {ECO:0000269|PubMed:11273702, ECO:0000269|PubMed:11404393,
CC ECO:0000269|PubMed:16966319}.
CC -!- INDUCTION: By bacterial lipopolysaccharides (LPS) in the monocytic
CC leukemia cell line THP-1. {ECO:0000269|PubMed:16966319}.
CC -!- PTM: Phosphorylated by a subset of GPR84-activating ligands.
CC Constitutively phosphorylated at Ser-221 and Ser-224 in the absence of
CC 2-HTP. By contrast, Thr-263 and Thr-264 are phosphorylated only
CC following prior cell treatment with 2-HTP.
CC {ECO:0000269|PubMed:35427647}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF282693; AAF91467.1; -; mRNA.
DR EMBL; AF237762; AAK01857.1; -; mRNA.
DR EMBL; FJ348261; ACI96305.1; -; mRNA.
DR EMBL; AB083586; BAB89299.1; -; Genomic_DNA.
DR EMBL; CH471054; EAW96776.1; -; Genomic_DNA.
DR EMBL; BC020614; AAH20614.1; -; mRNA.
DR CCDS; CCDS8878.1; -.
DR RefSeq; NP_065103.1; NM_020370.2.
DR RefSeq; XP_011536797.1; XM_011538495.2.
DR PDB; 8G05; EM; 3.00 A; R=1-387.
DR PDB; 8J18; EM; 2.89 A; R=1-396.
DR PDB; 8J19; EM; 3.23 A; R=1-396.
DR PDB; 8J1A; EM; 3.24 A; R=1-396.
DR PDBsum; 8G05; -.
DR PDBsum; 8J18; -.
DR PDBsum; 8J19; -.
DR PDBsum; 8J1A; -.
DR AlphaFoldDB; Q9NQS5; -.
DR EMDB; EMD-29645; -.
DR SMR; Q9NQS5; -.
DR BioGRID; 119803; 30.
DR IntAct; Q9NQS5; 1.
DR STRING; 9606.ENSP00000450310; -.
DR BindingDB; Q9NQS5; -.
DR ChEMBL; CHEMBL3714079; -.
DR GuidetoPHARMACOLOGY; 120; -.
DR GlyCosmos; Q9NQS5; 2 sites, No reported glycans.
DR GlyGen; Q9NQS5; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQS5; -.
DR PhosphoSitePlus; Q9NQS5; -.
DR BioMuta; GPR84; -.
DR DMDM; 66774035; -.
DR EPD; Q9NQS5; -.
DR MassIVE; Q9NQS5; -.
DR PaxDb; 9606-ENSP00000450310; -.
DR PeptideAtlas; Q9NQS5; -.
DR ProteomicsDB; 82180; -.
DR Antibodypedia; 15347; 363 antibodies from 30 providers.
DR DNASU; 53831; -.
DR Ensembl; ENST00000267015.4; ENSP00000267015.3; ENSG00000139572.4.
DR Ensembl; ENST00000551809.1; ENSP00000450310.1; ENSG00000139572.4.
DR GeneID; 53831; -.
DR KEGG; hsa:53831; -.
DR MANE-Select; ENST00000267015.4; ENSP00000267015.3; NM_020370.3; NP_065103.1.
DR UCSC; uc001sfu.4; human.
DR AGR; HGNC:4535; -.
DR CTD; 53831; -.
DR DisGeNET; 53831; -.
DR GeneCards; GPR84; -.
DR HGNC; HGNC:4535; GPR84.
DR HPA; ENSG00000139572; Tissue enhanced (bone marrow, urinary bladder).
DR MIM; 606383; gene.
DR neXtProt; NX_Q9NQS5; -.
DR OpenTargets; ENSG00000139572; -.
DR PharmGKB; PA28928; -.
DR VEuPathDB; HostDB:ENSG00000139572; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000161671; -.
DR HOGENOM; CLU_009579_3_10_1; -.
DR InParanoid; Q9NQS5; -.
DR OMA; QVLHMFC; -.
DR OrthoDB; 5392505at2759; -.
DR PhylomeDB; Q9NQS5; -.
DR TreeFam; TF333474; -.
DR PathwayCommons; Q9NQS5; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9NQS5; -.
DR SIGNOR; Q9NQS5; -.
DR BioGRID-ORCS; 53831; 14 hits in 1150 CRISPR screens.
DR GeneWiki; GPR84; -.
DR GenomeRNAi; 53831; -.
DR Pharos; Q9NQS5; Tchem.
DR PRO; PR:Q9NQS5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NQS5; Protein.
DR Bgee; ENSG00000139572; Expressed in bone marrow and 98 other cell types or tissues.
DR Genevisible; Q9NQS5; HS.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0001604; F:urotensin II receptor activity; IBA:GO_Central.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR CDD; cd15210; 7tmA_GPR84-like; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24230; G-PROTEIN COUPLED RECEPTOR; 1.
DR PANTHER; PTHR24230:SF59; G-PROTEIN COUPLED RECEPTOR 84; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; G-protein coupled receptor; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..396
FT /note="G-protein coupled receptor 84"
FT /id="PRO_0000069589"
FT TOPO_DOM 1..26
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..78
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..94
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..352
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..396
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 244..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35427647"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:35427647"
FT MOD_RES 263
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:35427647"
FT MOD_RES 264
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:35427647"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 37
FT /note="G -> D (in dbSNP:rs11170883)"
FT /id="VAR_049397"
FT VARIANT 367
FT /note="P -> R"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069393"
FT MUTAGEN 263
FT /note="T->A: More than 50% loss of interaction with ARR3."
FT /evidence="ECO:0000269|PubMed:35427647"
FT MUTAGEN 264
FT /note="T->A: More than 50% loss of interaction with ARR3."
FT /evidence="ECO:0000269|PubMed:35427647"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:8J19"
FT HELIX 20..47
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 56..71
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:8J18"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 91..123
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 134..152
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:8J18"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:8J18"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 176..212
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 316..341
FT /evidence="ECO:0007829|PDB:8J18"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:8J1A"
FT HELIX 351..369
FT /evidence="ECO:0007829|PDB:8J18"
FT TURN 370..372
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 375..387
FT /evidence="ECO:0007829|PDB:8J18"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:8J18"
SQ SEQUENCE 396 AA; 43705 MW; BEEA467DFEB7520B CRC64;
MWNSSDANFS CYHESVLGYR YVAVSWGVVV AVTGTVGNVL TLLALAIQPK LRTRFNLLIA
NLTLADLLYC TLLQPFSVDT YLHLHWRTGA TFCRVFGLLL FASNSVSILT LCLIALGRYL
LIAHPKLFPQ VFSAKGIVLA LVSTWVVGVA SFAPLWPIYI LVPVVCTCSF DRIRGRPYTT
ILMGIYFVLG LSSVGIFYCL IHRQVKRAAQ ALDQYKLRQA SIHSNHVART DEAMPGRFQE
LDSRLASGGP SEGISSEPVS AATTQTLEGD SSEVGDQINS KRAKQMAEKS PPEASAKAQP
IKGARRAPDS SSEFGKVTRM CFAVFLCFAL SYIPFLLLNI LDARVQAPRV VHMLAANLTW
LNGCINPVLY AAMNRQFRQA YGSILKRGPR SFHRLH
//
