ID   C5AR1_HUMAN             Reviewed;         350 AA.
AC   P21730;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 2.
DT   27-MAR-2024, entry version 214.
DE   RecName: Full=C5a anaphylatoxin chemotactic receptor 1;
DE   AltName: Full=C5a anaphylatoxin chemotactic receptor;
DE            Short=C5a-R;
DE            Short=C5aR;
DE   AltName: CD_antigen=CD88;
GN   Name=C5AR1; Synonyms=C5AR, C5R1;
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 VARIANTS ASN-2 AND ASN-279.
RX   PubMed=2007135; DOI=10.1021/bi00226a002;
RA   Boulay F., Mery L., Tardif M., Brouchon L., Vignais P.;
RT   "Expression cloning of a receptor for C5a anaphylatoxin on differentiated
RT   HL-60 cells.";
RL   Biochemistry 30:2993-2999(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS ASN-2 AND ASN-279.
RX   PubMed=1847994; DOI=10.1038/349614a0;
RA   Gerard N.P., Gerard C.;
RT   "The chemotactic receptor for human C5a anaphylatoxin.";
RL   Nature 349:614-617(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASN-2 AND ASN-279.
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 (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASN-2 AND ASN-279.
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ASN-2 AND ASN-279.
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-3, AND VARIANT ASN-2.
RX   PubMed=8383526; DOI=10.1021/bi00056a007;
RA   Gerard N.P., Bao L., Xiao-Ping H., Eddy R.L. Jr., Shows T.B., Gerard C.;
RT   "Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization
RT   of the human C5a receptor gene.";
RL   Biochemistry 32:1243-1250(1993).
RN   [8]
RP   FUNCTION, AND MUTAGENESIS OF 2-ASP--LEU-22; 2-ASP--SER-30; ASP-10; ASP-15;
RP   ASP-16; ASP-18 AND ASP-21.
RX   PubMed=8182049; DOI=10.1016/s0021-9258(17)36643-7;
RA   DeMartino J.A., Van Riper G., Siciliano S.J., Molineaux C.J.,
RA   Konteatis Z.D., Rosen H., Springer M.S.;
RT   "The amino terminus of the human C5a receptor is required for high affinity
RT   C5a binding and for receptor activation by C5a but not C5a analogs.";
RL   J. Biol. Chem. 269:14446-14450(1994).
RN   [9]
RP   FUNCTION, AND MUTAGENESIS OF GLU-199.
RX   PubMed=7622471; DOI=10.1074/jbc.270.28.16625;
RA   Monk P.N., Barker M.D., Partridge L.J., Pease J.E.;
RT   "Mutation of glutamate 199 of the human C5a receptor defines a binding site
RT   for ligand distinct from the receptor N terminus.";
RL   J. Biol. Chem. 270:16625-16629(1995).
RN   [10]
RP   PHOSPHORYLATION AT SER-314; SER-317; SER-327; SER-332; SER-334 AND SER-338.
RX   PubMed=7642584; DOI=10.1074/jbc.270.32.19166;
RA   Giannini E., Brouchon L., Boulay F.;
RT   "Identification of the major phosphorylation sites in human C5a
RT   anaphylatoxin receptor in vivo.";
RL   J. Biol. Chem. 270:19166-19172(1995).
RN   [11]
RP   FUNCTION AS A RECEPTOR FOR C5A.
RX   PubMed=9553099; DOI=10.1074/jbc.273.17.10411;
RA   Chen Z., Zhang X., Gonnella N.C., Pellas T.C., Boyar W.C., Ni F.;
RT   "Residues 21-30 within the extracellular N-terminal region of the C5a
RT   receptor represent a binding domain for the C5a anaphylatoxin.";
RL   J. Biol. Chem. 273:10411-10419(1998).
RN   [12]
RP   FUNCTION, AND PHOSPHORYLATION AT SER-314; SER-317; SER-327; SER-332;
RP   SER-334 AND SER-338.
RX   PubMed=10636859; DOI=10.1074/jbc.275.3.1656;
RA   Christophe T., Rabiet M.J., Tardif M., Milcent M.D., Boulay F.;
RT   "Human complement 5a (C5a) anaphylatoxin receptor (CD88) phosphorylation
RT   sites and their specific role in receptor phosphorylation and attenuation
RT   of G protein-mediated responses. Desensitization of C5a receptor controls
RT   superoxide production but not receptor sequestration in HL-60 cells.";
RL   J. Biol. Chem. 275:1656-1664(2000).
RN   [13]
RP   SULFATION AT TYR-11 AND TYR-14.
RX   PubMed=11342590; DOI=10.1084/jem.193.9.1059;
RA   Farzan M., Schnitzler C.E., Vasilieva N., Leung D., Kuhn J., Gerard C.,
RA   Gerard N.P., Choe H.;
RT   "Sulfated tyrosines contribute to the formation of the c5a docking site of
RT   the human c5a anaphylatoxin receptor.";
RL   J. Exp. Med. 193:1059-1066(2001).
RN   [14]
RP   INTERACTION WITH ARRB1 AND ARRB2, SUBCELLULAR LOCATION, AND
RP   PHOSPHORYLATION.
RX   PubMed=12464600; DOI=10.1074/jbc.m210120200;
RA   Braun L., Christophe T., Boulay F.;
RT   "Phosphorylation of key serine residues is required for internalization of
RT   the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin,
RT   dynamin, and clathrin-dependent pathway.";
RL   J. Biol. Chem. 278:4277-4285(2003).
RN   [15]
RP   SUBUNIT, AND MUTAGENESIS OF CYS-144; CYS-157 AND CYS-221.
RX   PubMed=12835319; DOI=10.1074/jbc.m305606200;
RA   Klco J.M., Lassere T.B., Baranski T.J.;
RT   "C5a receptor oligomerization. I. Disulfide trapping reveals oligomers and
RT   potential contact surfaces in a G protein-coupled receptor.";
RL   J. Biol. Chem. 278:35345-35353(2003).
RN   [16]
RP   FUNCTION, AND INTERACTION WITH CHIPS.
RX   PubMed=15153520; DOI=10.4049/jimmunol.172.11.6994;
RA   Postma B., Poppelier M.J.J.G., van Galen J.C., Prossnitz E.R.,
RA   van Strijp J.A.G., de Haas C.J.C., van Kessel K.P.M.;
RT   "Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically
RT   to the C5a and formylated peptide receptor.";
RL   J. Immunol. 172:6994-7001(2004).
RN   [17]
RP   INTERACTION WITH CHIPS, AND MUTAGENESIS OF ASP-10; GLY-12; TYR-14; ASP-15
RP   AND ASP-18.
RX   PubMed=15542591; DOI=10.1074/jbc.m412230200;
RA   Postma B., Kleibeuker W., Poppelier M.J.J.G., Boonstra M.,
RA   van Kessel K.P.M., van Strijp J.A.G., de Haas C.J.C.;
RT   "Residues 10-18 within the C5a receptor N terminus compose a binding domain
RT   for chemotaxis inhibitory protein of Staphylococcus aureus.";
RL   J. Biol. Chem. 280:2020-2027(2005).
RN   [18]
RP   INTERACTION WITH CHIPS, AND MUTAGENESIS OF TYR-11 AND TYR-14.
RX   PubMed=21706042; DOI=10.1038/aps.2011.53;
RA   Liu Z.J., Yang Y.J., Jiang L., Xu Y.C., Wang A.X., Du G.H., Gao J.M.;
RT   "Tyrosine sulfation in N-terminal domain of human C5a receptor is necessary
RT   for binding of chemotaxis inhibitory protein of Staphylococcus aureus.";
RL   Acta Pharmacol. Sin. 32:1038-1044(2011).
RN   [19] {ECO:0007744|PDB:5O9H}
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 31-333, FUNCTION, SUBCELLULAR
RP   LOCATION, TOPOLOGY, AND DISULFIDE BONDS.
RX   PubMed=29300009; DOI=10.1038/nature25025;
RA   Robertson N., Rappas M., Dore A.S., Brown J., Bottegoni G., Koglin M.,
RA   Cansfield J., Jazayeri A., Cooke R.M., Marshall F.H.;
RT   "Structure of the complement C5a receptor bound to the extra-helical
RT   antagonist NDT9513727.";
RL   Nature 553:111-114(2018).
CC   -!- FUNCTION: Receptor for the chemotactic and inflammatory peptide
CC       anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471,
CC       PubMed:9553099, PubMed:10636859, PubMed:15153520, PubMed:29300009). The
CC       ligand interacts with at least two sites on the receptor: a high-
CC       affinity site on the extracellular N-terminus, and a second site in the
CC       transmembrane region which activates downstream signaling events
CC       (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation
CC       stimulates chemotaxis, granule enzyme release, intracellular calcium
CC       release and superoxide anion production (PubMed:10636859,
CC       PubMed:15153520). {ECO:0000269|PubMed:10636859,
CC       ECO:0000269|PubMed:15153520, ECO:0000269|PubMed:1847994,
CC       ECO:0000269|PubMed:29300009, ECO:0000269|PubMed:7622471,
CC       ECO:0000269|PubMed:8182049, ECO:0000269|PubMed:9553099}.
CC   -!- SUBUNIT: Homodimer. May also form higher-order oligomers
CC       (PubMed:12835319). Interacts (when phosphorylated) with ARRB1 and
CC       ARRB2; the interaction is associated with internalization of C5aR
CC       (PubMed:12464600). Interacts (via N-terminal domain) with S.aureus
CC       chemotaxis inhibitory protein (CHIPS); the interaction blocks the
CC       receptor and may thus inhibit the immune response (PubMed:15153520,
CC       PubMed:15542591, PubMed:21706042). {ECO:0000269|PubMed:12464600,
CC       ECO:0000269|PubMed:12835319, ECO:0000269|PubMed:15153520,
CC       ECO:0000269|PubMed:15542591, ECO:0000269|PubMed:21706042,
CC       ECO:0000303|PubMed:12835319}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12464600,
CC       ECO:0000269|PubMed:29300009}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:29300009}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:12464600}. Note=Phosphorylated C5aR colocalizes
CC       with ARRB1 and ARRB2 in cytoplasmic vesicles.
CC       {ECO:0000269|PubMed:12464600}.
CC   -!- PTM: Sulfation plays a critical role in the association of C5aR with
CC       C5a, but no significant role in the ability of the receptor to
CC       transduce a signal and mobilize calcium in response to a small a small
CC       peptide agonist (PubMed:11342590). Sulfation at Tyr-14 is important for
CC       CHIPS binding (PubMed:21706042). {ECO:0000269|PubMed:11342590,
CC       ECO:0000303|PubMed:21706042}.
CC   -!- PTM: Phosphorylated on serine residues in response to C5a binding,
CC       resulting in internalization of the receptor and short-term
CC       desensitization to the ligand. The key residues involved in this
CC       process are Ser-334 and Ser-338. {ECO:0000269|PubMed:10636859,
CC       ECO:0000269|PubMed:12464600}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; M62505; AAA62831.1; -; mRNA.
DR   EMBL; X57250; CAA40530.1; -; mRNA.
DR   EMBL; X58674; CAB37830.1; -; Genomic_DNA.
DR   EMBL; AY221091; AAO65969.1; -; Genomic_DNA.
DR   EMBL; BT007358; AAP36022.1; -; mRNA.
DR   EMBL; AC099491; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC008982; AAH08982.1; -; mRNA.
DR   EMBL; S56556; AAD14919.1; -; Genomic_DNA.
DR   EMBL; S56557; AAD14919.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS33063.1; -.
DR   PIR; A37963; A37963.
DR   RefSeq; NP_001727.1; NM_001736.3.
DR   PDB; 2K3U; NMR; -; B=7-28.
DR   PDB; 5O9H; X-ray; 2.70 A; A/B=31-333.
DR   PDB; 6C1Q; X-ray; 2.90 A; B=30-331.
DR   PDB; 6C1R; X-ray; 2.20 A; B=30-331.
DR   PDB; 7Y64; EM; 2.90 A; D=1-330.
DR   PDB; 7Y65; EM; 3.20 A; D=1-330.
DR   PDB; 7Y66; EM; 2.90 A; D=1-330.
DR   PDB; 7Y67; EM; 2.80 A; D=1-330.
DR   PDB; 8GO8; EM; 3.41 A; U/V=331-350.
DR   PDB; 8GOO; EM; 4.40 A; G/U/V=331-350.
DR   PDB; 8HK5; EM; 3.00 A; A=1-350.
DR   PDB; 8I0N; EM; 3.26 A; U/V=334-342.
DR   PDB; 8I0Z; EM; 4.33 A; G/U/V=331-350.
DR   PDB; 8IA2; EM; 3.21 A; A=2-350.
DR   PDB; 8JZZ; EM; 3.31 A; A=2-350.
DR   PDBsum; 2K3U; -.
DR   PDBsum; 5O9H; -.
DR   PDBsum; 6C1Q; -.
DR   PDBsum; 6C1R; -.
DR   PDBsum; 7Y64; -.
DR   PDBsum; 7Y65; -.
DR   PDBsum; 7Y66; -.
DR   PDBsum; 7Y67; -.
DR   PDBsum; 8GO8; -.
DR   PDBsum; 8GOO; -.
DR   PDBsum; 8HK5; -.
DR   PDBsum; 8I0N; -.
DR   PDBsum; 8I0Z; -.
DR   PDBsum; 8IA2; -.
DR   PDBsum; 8JZZ; -.
DR   AlphaFoldDB; P21730; -.
DR   EMDB; EMD-33633; -.
DR   EMDB; EMD-33634; -.
DR   EMDB; EMD-33635; -.
DR   EMDB; EMD-33636; -.
DR   EMDB; EMD-34846; -.
DR   EMDB; EMD-35292; -.
DR   EMDB; EMD-36755; -.
DR   SMR; P21730; -.
DR   BioGRID; 107189; 159.
DR   IntAct; P21730; 1.
DR   STRING; 9606.ENSP00000347197; -.
DR   BindingDB; P21730; -.
DR   ChEMBL; CHEMBL2373; -.
DR   DrugBank; DB15011; Avacopan.
DR   GuidetoPHARMACOLOGY; 32; -.
DR   TCDB; 9.A.14.13.26; the g-protein-coupled receptor (gpcr) family.
DR   GlyCosmos; P21730; 1 site, No reported glycans.
DR   GlyGen; P21730; 1 site.
DR   iPTMnet; P21730; -.
DR   PhosphoSitePlus; P21730; -.
DR   BioMuta; C5AR1; -.
DR   DMDM; 311033355; -.
DR   jPOST; P21730; -.
DR   MassIVE; P21730; -.
DR   PaxDb; 9606-ENSP00000347197; -.
DR   PeptideAtlas; P21730; -.
DR   ProteomicsDB; 53893; -.
DR   ABCD; P21730; 5 sequenced antibodies.
DR   Antibodypedia; 2966; 1124 antibodies from 38 providers.
DR   DNASU; 728; -.
DR   Ensembl; ENST00000355085.4; ENSP00000347197.2; ENSG00000197405.8.
DR   GeneID; 728; -.
DR   KEGG; hsa:728; -.
DR   MANE-Select; ENST00000355085.4; ENSP00000347197.2; NM_001736.4; NP_001727.2.
DR   UCSC; uc002pgj.2; human.
DR   AGR; HGNC:1338; -.
DR   CTD; 728; -.
DR   DisGeNET; 728; -.
DR   GeneCards; C5AR1; -.
DR   HGNC; HGNC:1338; C5AR1.
DR   HPA; ENSG00000197405; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 113995; gene.
DR   neXtProt; NX_P21730; -.
DR   OpenTargets; ENSG00000197405; -.
DR   PharmGKB; PA25920; -.
DR   VEuPathDB; HostDB:ENSG00000197405; -.
DR   eggNOG; ENOG502R35Z; Eukaryota.
DR   GeneTree; ENSGT01100000263564; -.
DR   HOGENOM; CLU_009579_8_0_1; -.
DR   InParanoid; P21730; -.
DR   OMA; VAVWCLA; -.
DR   OrthoDB; 4264357at2759; -.
DR   PhylomeDB; P21730; -.
DR   TreeFam; TF330976; -.
DR   PathwayCommons; P21730; -.
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-977606; Regulation of Complement cascade.
DR   SignaLink; P21730; -.
DR   SIGNOR; P21730; -.
DR   BioGRID-ORCS; 728; 12 hits in 1141 CRISPR screens.
DR   ChiTaRS; C5AR1; human.
DR   GeneWiki; C5a_receptor; -.
DR   GenomeRNAi; 728; -.
DR   Pharos; P21730; Tclin.
DR   PRO; PR:P21730; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; P21730; Protein.
DR   Bgee; ENSG00000197405; Expressed in blood and 144 other cell types or tissues.
DR   ExpressionAtlas; P21730; baseline and differential.
DR   GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR   GO; GO:0004878; F:complement component C5a receptor activity; IDA:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IPI:UniProtKB.
DR   GO; GO:0007202; P:activation of phospholipase C activity; TAS:ProtInc.
DR   GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL.
DR   GO; GO:0048143; P:astrocyte activation; ISS:ARUK-UCL.
DR   GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR   GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR   GO; GO:0050890; P:cognition; ISS:ARUK-UCL.
DR   GO; GO:0038178; P:complement component C5a signaling pathway; IDA:UniProtKB.
DR   GO; GO:0002430; P:complement receptor mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0001774; P:microglial cell activation; ISS:ARUK-UCL.
DR   GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0030593; P:neutrophil chemotaxis; IEA:Ensembl.
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:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
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   GO; GO:0099172; P:presynapse organization; ISS:ARUK-UCL.
DR   GO; GO:1902947; P:regulation of tau-protein kinase activity; ISS:ARUK-UCL.
DR   GO; GO:0032494; P:response to peptidoglycan; IEA:Ensembl.
DR   GO; GO:0007606; P:sensory perception of chemical stimulus; TAS:ProtInc.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd15114; 7tmA_C5aR; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
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:SF29; C5A ANAPHYLATOXIN CHEMOTACTIC RECEPTOR 1; 1.
DR   PANTHER; PTHR24225; CHEMOTACTIC RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR01104; ANPHYLATOXNR.
DR   PRINTS; PR00426; C5ANPHYLTXNR.
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; P21730; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Chemotaxis; Cytoplasmic vesicle;
KW   Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW   Phosphoprotein; Receptor; Reference proteome; Sulfation; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..350
FT                   /note="C5a anaphylatoxin chemotactic receptor 1"
FT                   /id="PRO_0000069209"
FT   TOPO_DOM        1..37
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        38..64
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        65..69
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        70..93
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        94..110
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        111..132
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        133..153
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        154..174
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        175..200
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        201..226
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        227..242
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        243..265
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        266..282
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TRANSMEM        283..303
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   TOPO_DOM        304..350
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:29300009"
FT   REGION          10..18
FT                   /note="Required for CHIPS binding"
FT                   /evidence="ECO:0000269|PubMed:15542591"
FT   REGION          21..30
FT                   /note="Involved in C5a binding"
FT                   /evidence="ECO:0000269|PubMed:9553099"
FT   MOD_RES         11
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:11342590"
FT   MOD_RES         14
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:11342590"
FT   MOD_RES         314
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000305|PubMed:7642584"
FT   MOD_RES         317
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10636859,
FT                   ECO:0000269|PubMed:7642584"
FT   MOD_RES         327
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10636859,
FT                   ECO:0000269|PubMed:7642584"
FT   MOD_RES         332
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10636859,
FT                   ECO:0000269|PubMed:7642584"
FT   MOD_RES         334
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10636859,
FT                   ECO:0000269|PubMed:7642584"
FT   MOD_RES         338
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10636859,
FT                   ECO:0000269|PubMed:7642584"
FT   CARBOHYD        5
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        109..188
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT                   ECO:0000269|PubMed:29300009, ECO:0007744|PDB:5O9H"
FT   VARIANT         2
FT                   /note="D -> N (in dbSNP:rs4467185)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:1847994, ECO:0000269|PubMed:2007135,
FT                   ECO:0000269|PubMed:8383526, ECO:0000269|Ref.3,
FT                   ECO:0000269|Ref.4"
FT                   /id="VAR_049377"
FT   VARIANT         279
FT                   /note="K -> N (in dbSNP:rs11880097)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:1847994, ECO:0000269|PubMed:2007135,
FT                   ECO:0000269|Ref.3, ECO:0000269|Ref.4"
FT                   /id="VAR_049378"
FT   MUTAGEN         2..30
FT                   /note="Missing: Strongly impairs C5a binding
FT                   (45,000-fold)."
FT                   /evidence="ECO:0000269|PubMed:8182049"
FT   MUTAGEN         2..22
FT                   /note="Missing: Impairs C5a binding. Strongly impairs C5a
FT                   binding; when associated with A-27."
FT                   /evidence="ECO:0000269|PubMed:8182049"
FT   MUTAGEN         10
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with A-15; A-16; A-18 and A-21 (PubMed:8182049). Moderately
FT                   impairs CHIPS binding (PubMed:15542591). Strongly impairs
FT                   CHIPS binding; when associated with A-15 (PubMed:15542591).
FT                   Strongly impairs CHIPS binding; when associated with A-18
FT                   (PubMed:15542591)."
FT                   /evidence="ECO:0000269|PubMed:15542591,
FT                   ECO:0000269|PubMed:8182049"
FT   MUTAGEN         11
FT                   /note="Y->F: Weakly impairs CHIPS binding. Loss of CHIPS
FT                   binding; when associated with F-14."
FT                   /evidence="ECO:0000269|PubMed:21706042"
FT   MUTAGEN         12
FT                   /note="G->A: Moderately impairs CHIPS binding."
FT                   /evidence="ECO:0000269|PubMed:15542591"
FT   MUTAGEN         14
FT                   /note="Y->F: Weakly impairs CHIPS binding
FT                   (PubMed:15542591). Strongly impairs CHIPS binding
FT                   (PubMed:21706042). Loss of CHIPS binding; when associated
FT                   with F-11 (PubMed:21706042)."
FT                   /evidence="ECO:0000269|PubMed:15542591,
FT                   ECO:0000269|PubMed:21706042"
FT   MUTAGEN         15
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with A-10; A-16; A-18 and A-21 (PubMed:8182049). Moderately
FT                   impairs CHIPS binding (PubMed:15542591). Strongly impairs
FT                   CHIPS binding; when associated with A-10 (PubMed:15542591).
FT                   Strongly impairs CHIPS binding; when associated with A-18
FT                   (PubMed:15542591)."
FT                   /evidence="ECO:0000269|PubMed:15542591,
FT                   ECO:0000269|PubMed:8182049"
FT   MUTAGEN         16
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with A-10; A-15; A-18 and A-21."
FT                   /evidence="ECO:0000269|PubMed:8182049"
FT   MUTAGEN         18
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with A-10; A-15; A-16 and A-21 (PubMed:8182049). Impairs
FT                   CHIPS binding (PubMed:15542591). Strongly impairs CHIPS
FT                   binding; when associated with A-10 (PubMed:15542591).
FT                   Strongly impairs CHIPS binding; when associated with A-15
FT                   (PubMed:15542591)."
FT                   /evidence="ECO:0000269|PubMed:15542591,
FT                   ECO:0000269|PubMed:8182049"
FT   MUTAGEN         21
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with A-10; A-15; A-16 and A-18."
FT                   /evidence="ECO:0000269|PubMed:8182049"
FT   MUTAGEN         27
FT                   /note="D->A: Strongly impairs C5a binding; when associated
FT                   with 2-D--L-22 Del."
FT                   /evidence="ECO:0000269|PubMed:8182049"
FT   MUTAGEN         144
FT                   /note="C->S: Fails to homodimerize."
FT                   /evidence="ECO:0000269|PubMed:12835319"
FT   MUTAGEN         157
FT                   /note="C->S: No effect on homodimer formation."
FT                   /evidence="ECO:0000269|PubMed:12835319"
FT   MUTAGEN         199
FT                   /note="E->Q: Impairs C5a binding (10-fold reduction) and
FT                   C5a-induced 5-HT secretion."
FT                   /evidence="ECO:0000269|PubMed:7622471"
FT   MUTAGEN         221
FT                   /note="C->S: No effect on homodimer formation."
FT                   /evidence="ECO:0000269|PubMed:12835319"
FT   HELIX           35..65
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   TURN            66..68
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           70..86
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           89..97
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   TURN            98..100
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           106..111
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           112..114
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           115..139
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           141..146
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           150..173
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   STRAND          175..180
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   TURN            181..184
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   STRAND          185..190
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           196..210
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           212..230
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   STRAND          233..235
FT                   /evidence="ECO:0007829|PDB:5O9H"
FT   HELIX           238..266
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   STRAND          270..272
FT                   /evidence="ECO:0007829|PDB:7Y67"
FT   HELIX           273..280
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           282..289
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           292..305
FT                   /evidence="ECO:0007829|PDB:6C1R"
FT   HELIX           307..313
FT                   /evidence="ECO:0007829|PDB:7Y67"
FT   HELIX           315..323
FT                   /evidence="ECO:0007829|PDB:6C1R"
SQ   SEQUENCE   350 AA;  39336 MW;  9334BB39A2C96D3D CRC64;
     MDSFNYTTPD YGHYDDKDTL DLNTPVDKTS NTLRVPDILA LVIFAVVFLV GVLGNALVVW
     VTAFEAKRTI NAIWFLNLAV ADFLSCLALP ILFTSIVQHH HWPFGGAACS ILPSLILLNM
     YASILLLATI SADRFLLVFK PIWCQNFRGA GLAWIACAVA WGLALLLTIP SFLYRVVREE
     YFPPKVLCGV DYSHDKRRER AVAIVRLVLG FLWPLLTLTI CYTFILLRTW SRRATRSTKT
     LKVVVAVVAS FFIFWLPYQV TGIMMSFLEP SSPTFLLLKK LDSLCVSFAY INCCINPIIY
     VVAGQGFQGR LRKSLPSLLR NVLTEESVVR ESKSFTRSTV DTMAQKTQAV
//