ID   C3AR_HUMAN              Reviewed;         482 AA.
AC   Q16581; O43771; Q92868;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2003, sequence version 2.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=C3a anaphylatoxin chemotactic receptor;
DE            Short=C3AR;
DE            Short=C3a-R;
GN   Name=C3AR1; Synonyms=AZ3B, C3R1, HNFAG09;
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].
RX   PubMed=8605247; DOI=10.1016/0167-4781(95)00209-x;
RA   Roglic A., Prossnitz E.R., Cavanagh S.L., Pan Z., Zou A., Ye R.D.;
RT   "cDNA cloning of a novel G protein-coupled receptor with a large
RT   extracellular loop structure.";
RL   Biochim. Biophys. Acta 1305:39-43(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8765043; DOI=10.1002/eji.1830260840;
RA   Crass T., Raffetseder U., Martin U., Grove M., Klos A., Koehl J.,
RA   Bautsch W.;
RT   "Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from
RT   differentiated U-937 cells.";
RL   Eur. J. Immunol. 26:1944-1950(1996).
RN   [3]
RP   SEQUENCE REVISION.
RA   Bautsch W.;
RL   Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8702752; DOI=10.1074/jbc.271.34.20231;
RA   Ames R.S., Li Y., Sarau H.M., Nuthulaganti P., Foley J.J., Ellis C.,
RA   Zeng Z., Su K., Jurewicz A.J., Hertzberg R.P., Bergsma D.J., Kumar C.;
RT   "Molecular cloning and characterization of the human anaphylatoxin C3a
RT   receptor.";
RL   J. Biol. Chem. 271:20231-20234(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA   Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT   "Genome-wide discovery and analysis of human seven transmembrane helix
RT   receptor genes.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT   "cDNA clones of human proteins involved in signal transduction sequenced by
RT   the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-136.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [9]
RP   SULFATION AT TYR-174; TYR-184 AND TYR-318.
RX   PubMed=12871936; DOI=10.1074/jbc.m306061200;
RA   Gao J., Choe H., Bota D., Wright P.L., Gerard C., Gerard N.P.;
RT   "Sulfation of tyrosine 174 in the human C3a receptor is essential for
RT   binding of C3a anaphylatoxin.";
RL   J. Biol. Chem. 278:37902-37908(2003).
RN   [10]
RP   GLYCOSYLATION AT SER-266, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=23234360; DOI=10.1021/pr300963h;
RA   Halim A., Ruetschi U., Larson G., Nilsson J.;
RT   "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT   of human cerebrospinal fluid glycoproteins.";
RL   J. Proteome Res. 12:573-584(2013).
CC   -!- FUNCTION: Receptor for the chemotactic and inflammatory peptide
CC       anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme
CC       release and superoxide anion production.
CC   -!- SUBUNIT: Interacts with VGF-derived peptide TLQP-21 (By similarity).
CC       {ECO:0000250|UniProtKB:O09047}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Widely expressed in several differentiated
CC       hematopoietic cell lines, in the lung, spleen, ovary, placenta, small
CC       intestine, throughout the brain, heart, and endothelial cells. Mostly
CC       expressed in lymphoid tissues.
CC   -!- PTM: Among the sulfation sites Tyr-174 is essential for binding of C3a
CC       anaphylatoxin. {ECO:0000269|PubMed:12871936}.
CC   -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/c3ar1/";
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DR   EMBL; U28488; AAC50374.1; -; mRNA.
DR   EMBL; Z73157; CAA97504.1; -; mRNA.
DR   EMBL; U62027; AAC50657.1; -; mRNA.
DR   EMBL; AB065870; BAC06088.1; -; Genomic_DNA.
DR   EMBL; AY268431; AAP23198.1; -; Genomic_DNA.
DR   EMBL; AY455929; AAR13862.1; -; Genomic_DNA.
DR   EMBL; BC020742; AAH20742.1; -; mRNA.
DR   CCDS; CCDS8588.1; -.
DR   PIR; S65766; S65766.
DR   RefSeq; NP_001313404.1; NM_001326475.1.
DR   RefSeq; NP_001313406.1; NM_001326477.1.
DR   RefSeq; NP_004045.1; NM_004054.3.
DR   PDB; 8HK2; EM; 2.90 A; A=1-476.
DR   PDB; 8HK3; EM; 3.20 A; C=1-476.
DR   PDB; 8I95; EM; 2.88 A; C=2-482.
DR   PDB; 8I97; EM; 3.19 A; C=2-482.
DR   PDB; 8I9A; EM; 3.57 A; C=2-482.
DR   PDB; 8I9L; EM; 3.18 A; C=2-482.
DR   PDB; 8I9S; EM; 3.26 A; C=2-482.
DR   PDB; 8IA8; EM; 2.86 A; A=1-482.
DR   PDB; 8J6D; EM; 3.10 A; C=2-482.
DR   PDBsum; 8HK2; -.
DR   PDBsum; 8HK3; -.
DR   PDBsum; 8I95; -.
DR   PDBsum; 8I97; -.
DR   PDBsum; 8I9A; -.
DR   PDBsum; 8I9L; -.
DR   PDBsum; 8I9S; -.
DR   PDBsum; 8IA8; -.
DR   PDBsum; 8J6D; -.
DR   AlphaFoldDB; Q16581; -.
DR   EMDB; EMD-34842; -.
DR   EMDB; EMD-34843; -.
DR   EMDB; EMD-35257; -.
DR   EMDB; EMD-35259; -.
DR   EMDB; EMD-35263; -.
DR   EMDB; EMD-35275; -.
DR   EMDB; EMD-35282; -.
DR   EMDB; EMD-35298; -.
DR   EMDB; EMD-36001; -.
DR   SMR; Q16581; -.
DR   BioGRID; 107180; 124.
DR   IntAct; Q16581; 91.
DR   STRING; 9606.ENSP00000302079; -.
DR   BindingDB; Q16581; -.
DR   ChEMBL; CHEMBL4761; -.
DR   GuidetoPHARMACOLOGY; 31; -.
DR   GlyConnect; 811; 1 O-Linked glycan (1 site).
DR   GlyCosmos; Q16581; 5 sites, 2 glycans.
DR   GlyGen; Q16581; 5 sites, 2 O-linked glycans (3 sites).
DR   iPTMnet; Q16581; -.
DR   PhosphoSitePlus; Q16581; -.
DR   BioMuta; C3AR1; -.
DR   DMDM; 37538305; -.
DR   CPTAC; CPTAC-1177; -.
DR   jPOST; Q16581; -.
DR   MassIVE; Q16581; -.
DR   PaxDb; 9606-ENSP00000302079; -.
DR   PeptideAtlas; Q16581; -.
DR   ProteomicsDB; 60928; -.
DR   ABCD; Q16581; 16 sequenced antibodies.
DR   Antibodypedia; 3999; 594 antibodies from 34 providers.
DR   DNASU; 719; -.
DR   Ensembl; ENST00000307637.5; ENSP00000302079.4; ENSG00000171860.5.
DR   GeneID; 719; -.
DR   KEGG; hsa:719; -.
DR   MANE-Select; ENST00000307637.5; ENSP00000302079.4; NM_004054.4; NP_004045.1.
DR   UCSC; uc001qtv.2; human.
DR   AGR; HGNC:1319; -.
DR   CTD; 719; -.
DR   DisGeNET; 719; -.
DR   GeneCards; C3AR1; -.
DR   HGNC; HGNC:1319; C3AR1.
DR   HPA; ENSG00000171860; Tissue enhanced (lymphoid).
DR   MIM; 605246; gene.
DR   neXtProt; NX_Q16581; -.
DR   OpenTargets; ENSG00000171860; -.
DR   PharmGKB; PA25898; -.
DR   VEuPathDB; HostDB:ENSG00000171860; -.
DR   eggNOG; ENOG502R35Z; Eukaryota.
DR   GeneTree; ENSGT01100000263564; -.
DR   HOGENOM; CLU_009579_35_0_1; -.
DR   InParanoid; Q16581; -.
DR   OMA; MKPVWCQ; -.
DR   OrthoDB; 5356571at2759; -.
DR   PhylomeDB; Q16581; -.
DR   TreeFam; TF330976; -.
DR   PathwayCommons; Q16581; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR   Reactome; R-HSA-977606; Regulation of Complement cascade.
DR   SignaLink; Q16581; -.
DR   SIGNOR; Q16581; -.
DR   BioGRID-ORCS; 719; 8 hits in 1159 CRISPR screens.
DR   ChiTaRS; C3AR1; human.
DR   GeneWiki; C3a_receptor; -.
DR   GenomeRNAi; 719; -.
DR   Pharos; Q16581; Tchem.
DR   PRO; PR:Q16581; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q16581; Protein.
DR   Bgee; ENSG00000171860; Expressed in monocyte and 180 other cell types or tissues.
DR   ExpressionAtlas; Q16581; baseline and differential.
DR   GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR   GO; GO:0004876; F:complement component C3a receptor activity; IDA:UniProtKB.
DR   GO; GO:0004878; F:complement component C5a receptor activity; IBA:GO_Central.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IPI:UniProtKB.
DR   GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR   GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB.
DR   GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR   GO; GO:0002430; P:complement receptor mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR   GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
DR   GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IEA:Ensembl.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IEA:Ensembl.
DR   CDD; cd15115; 7tmA_C3aR; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2.
DR   InterPro; IPR001644; Anaphtx_C3AR1.
DR   InterPro; IPR002234; Anphylx_rcpt_C3a/C5a1-2.
DR   InterPro; IPR000826; Formyl_rcpt-rel.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24225:SF28; C3A ANAPHYLATOXIN CHEMOTACTIC RECEPTOR; 1.
DR   PANTHER; PTHR24225; CHEMOTACTIC RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 2.
DR   PRINTS; PR01104; ANPHYLATOXNR.
DR   PRINTS; PR01060; C3ANPHYLTXNR.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; Q16581; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Chemotaxis; Disulfide bond;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
KW   Receptor; Reference proteome; Sulfation; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..482
FT                   /note="C3a anaphylatoxin chemotactic receptor"
FT                   /id="PRO_0000069202"
FT   TOPO_DOM        1..23
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        24..46
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        47..57
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        58..80
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        81..96
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..118
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        119..139
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        140..160
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        161..340
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        341..360
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        361..377
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        378..400
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        401..417
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        418..438
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        439..482
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         174
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12871936"
FT   MOD_RES         184
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12871936"
FT   MOD_RES         318
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12871936"
FT   MOD_RES         459
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O09047"
FT   MOD_RES         463
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O09047"
FT   CARBOHYD        9
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        266
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:23234360"
FT   DISULFID        95..172
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         136
FT                   /note="V -> A (in dbSNP:rs11567806)"
FT                   /evidence="ECO:0000269|Ref.7"
FT                   /id="VAR_019164"
FT   CONFLICT        151
FT                   /note="F -> C (in Ref. 4; AAC50657)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        203
FT                   /note="P -> R (in Ref. 1; AAC50374)"
FT                   /evidence="ECO:0000305"
FT   HELIX           21..50
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           56..83
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   TURN            84..86
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           94..125
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           127..133
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           136..153
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           155..160
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   STRAND          162..166
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   STRAND          169..173
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           333..344
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           346..364
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   STRAND          365..368
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           374..401
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   STRAND          405..407
FT                   /evidence="ECO:0007829|PDB:8HK3"
FT   HELIX           408..435
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   TURN            436..438
FT                   /evidence="ECO:0007829|PDB:8HK2"
FT   HELIX           440..453
FT                   /evidence="ECO:0007829|PDB:8HK2"
SQ   SEQUENCE   482 AA;  53864 MW;  287E219D98CED203 CRC64;
     MASFSAETNS TDLLSQPWNE PPVILSMVIL SLTFLLGLPG NGLVLWVAGL KMQRTVNTIW
     FLHLTLADLL CCLSLPFSLA HLALQGQWPY GRFLCKLIPS IIVLNMFASV FLLTAISLDR
     CLVVFKPIWC QNHRNVGMAC SICGCIWVVA FVMCIPVFVY REIFTTDNHN RCGYKFGLSS
     SLDYPDFYGD PLENRSLENI VQPPGEMNDR LDPSSFQTND HPWTVPTVFQ PQTFQRPSAD
     SLPRGSARLT SQNLYSNVFK PADVVSPKIP SGFPIEDHET SPLDNSDAFL STHLKLFPSA
     SSNSFYESEL PQGFQDYYNL GQFTDDDQVP TPLVAITITR LVVGFLLPSV IMIACYSFIV
     FRMQRGRFAK SQSKTFRVAV VVVAVFLVCW TPYHIFGVLS LLTDPETPLG KTLMSWDHVC
     IALASANSCF NPFLYALLGK DFRKKARQSI QGILEAAFSE ELTRSTHCPS NNVISERNST
     TV
//