C5AR1_HUMAN
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 03-AUG-2022, entry version 205.
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; 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 PDBsum; 5O9H; -.
DR PDBsum; 6C1Q; -.
DR PDBsum; 6C1R; -.
DR AlphaFoldDB; P21730; -.
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 GlyGen; P21730; 1 site.
DR iPTMnet; P21730; -.
DR PhosphoSitePlus; P21730; -.
DR BioMuta; C5AR1; -.
DR DMDM; 311033355; -.
DR jPOST; P21730; -.
DR MassIVE; P21730; -.
DR PaxDb; P21730; -.
DR PeptideAtlas; P21730; -.
DR PRIDE; P21730; -.
DR ProteomicsDB; 53893; -.
DR ABCD; P21730; 5 sequenced antibodies.
DR Antibodypedia; 2966; 1016 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 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; ENSGT01020000230336; -.
DR HOGENOM; CLU_009579_8_0_1; -.
DR InParanoid; P21730; -.
DR OMA; YTFLLIR; -.
DR OrthoDB; 978188at2759; -.
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; 11 hits in 1064 CRISPR screens.
DR ChiTaRS; C5AR1; human.
DR GeneWiki; C5a_receptor; -.
DR GenomeRNAi; 728; -.
DR Pharos; P21730; Tchem.
DR PRO; PR:P21730; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P21730; protein.
DR Bgee; ENSG00000197405; Expressed in blood and 142 other tissues.
DR ExpressionAtlas; P21730; baseline and differential.
DR Genevisible; P21730; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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:0004875; F:complement receptor activity; IBA:GO_Central.
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 InterPro; IPR001274; Anaphtx_C5AR1/C5AR2.
DR InterPro; IPR002234; Anphylx_rcpt.
DR InterPro; IPR000826; Formyl_rcpt-rel.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24225; PTHR24225; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01104; ANPHYLATOXNR.
DR PRINTS; PR00426; C5ANPHYLTXNR.
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; 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 (45,000-
FT 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 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 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
