C5a anaphylatoxin chemotactic receptor 1

Details

Name
C5a anaphylatoxin chemotactic receptor 1
Synonyms
  • C5a anaphylatoxin chemotactic receptor
  • C5a-R
  • C5AR
  • C5R1
Gene Name
C5AR1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052628|C5a anaphylatoxin chemotactic receptor 1
MDSFNYTTPDYGHYDDKDTLDLNTPVDKTSNTLRVPDILALVIFAVVFLVGVLGNALVVW
VTAFEAKRTINAIWFLNLAVADFLSCLALPILFTSIVQHHHWPFGGAACSILPSLILLNM
YASILLLATISADRFLLVFKPIWCQNFRGAGLAWIACAVAWGLALLLTIPSFLYRVVREE
YFPPKVLCGVDYSHDKRRERAVAIVRLVLGFLWPLLTLTICYTFILLRTWSRRATRSTKT
LKVVVAVVASFFIFWLPYQVTGIMMSFLEPSSPTFLLLKKLDSLCVSFAYINCCINPIIY
VVAGQGFQGRLRKSLPSLLRNVLTEESVVRESKSFTRSTVDTMAQKTQAV
Number of residues
350
Molecular Weight
39335.065
Theoretical pI
Not Available
GO Classification
Functions
complement component C5a binding / complement component C5a receptor activity / complement receptor activity / G protein-coupled receptor activity
Processes
activation of MAPK activity / activation of phospholipase C activity / amyloid-beta clearance / animal organ regeneration / apoptotic process / astrocyte activation / cell proliferation in hindbrain / cellular defense response / chemotaxis / cognition / complement component C5a signaling pathway / complement receptor mediated signaling pathway / defense response to Gram-positive bacterium / G protein-coupled receptor signaling pathway / immune response / inflammatory response / microglial cell activation / mRNA transcription by RNA polymerase II / negative regulation of neuron apoptotic process / neutrophil chemotaxis / neutrophil degranulation / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of angiogenesis / positive regulation of cytosolic calcium ion concentration / positive regulation of epithelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of macrophage chemotaxis / positive regulation of neutrophil chemotaxis / positive regulation of vascular endothelial growth factor production / presynapse organization / regulation of complement activation / regulation of tau-protein kinase activity / response to lipopolysaccharide / response to peptidoglycan / sensory perception of chemical stimulus / signal transduction
Components
apical part of cell / basolateral plasma membrane / cell surface / integral component of plasma membrane / plasma membrane / secretory granule membrane
General Function
Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a (PubMed:1847994, PubMed:8182049, PubMed:7622471, PubMed:9553099, PubMed:10636859, PubMed:15153520, PubMed:29300009). The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events (PubMed:8182049, PubMed:7622471, PubMed:9553099). Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production (PubMed:10636859, PubMed:15153520).
Specific Function
Complement component c5a binding
Pfam Domain Function
Transmembrane Regions
38-64 70-93 111-132 154-174 201-226 243-265 283-303
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052629|C5a anaphylatoxin chemotactic receptor 1 (C5AR1)
ATGGACTCCTTCAATTATACCACCCCTGATTATGGGCACTATGATGACAAGGATACCCTG
GACCTCAACACCCCTGTGGATAAAACTTCTAACACGCTGCGTGTTCCAGACATCCTGGCC
TTGGTCATCTTTGCAGTCGTCTTCCTGGTGGGAGTGCTGGGCAATGCCCTGGTGGTCTGG
GTGACGGCATTCGAGGCCAAGCGGACCATCAATGCCATCTGGTTCCTCAACTTGGCGGTA
GCCGACTTCCTCTCCTGCCTGGCGCTGCCCATCTTGTTCACGTCCATTGTACAGCATCAC
CACTGGCCCTTTGGCGGGGCCGCCTGCAGCATCCTGCCCTCCCTCATCCTGCTCAACATG
TACGCCAGCATCCTGCTCCTGGCCACCATCAGCGCCGACCGCTTTCTGCTGGTGTTTAAA
CCCATCTGGTGCCAGAACTTCCGAGGGGCTGGCTTGGCCTGGATCGCCTGTGCCGTGGCT
TGGGGTTTAGCCCTGCTGCTGACCATACCCTCCTTCCTGTACCGGGTGGTCCGGGAGGAG
TACTTTCCACCAAAGGTGTTGTGTGGCGTGGACTACAGCCACGACAAACGGCGGGAGCGA
GCCGTGGCCATCGTCCGGCTGGTCCTGGGCTTCCTGTGGCCTCTACTCACGCTCACGATT
TGTTACACTTTCATCCTGCTCCGGACGTGGAGCCGCAGGGCCACGCGGTCCACCAAGACA
CTCAAGGTGGTGGTGGCAGTGGTGGCCAGTTTCTTTATCTTCTGGTTGCCCTACCAGGTG
ACGGGGATAATGATGTCCTTCCTGGAGCCATCGTCACCCACCTTCCTGCTGCTGAAGAAG
CTGGACTCCCTGTGTGTCTCCTTTGCCTACATCAACTGCTGCATCAACCCCATCATCTAC
GTGGTGGCCGGCCAGGGCTTCCAGGGCCGACTGCGGAAATCCCTCCCCAGCCTCCTCCGG
AACGTGTTGACTGAAGAGTCCGTGGTTAGGGAGAGCAAGTCATTCACGCGCTCCACAGTG
GACACTATGGCCCAGAAGACCCAGGCAGTGTAG
Chromosome Location
19
Locus
19q13.32
External Identifiers
ResourceLink
UniProtKB IDP21730
UniProtKB Entry NameC5AR1_HUMAN
HGNC IDHGNC:1338
General References
  1. Boulay F, Mery L, Tardif M, Brouchon L, Vignais P: Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cells. Biochemistry. 1991 Mar 26;30(12):2993-9. [Article]
  2. Gerard NP, Gerard C: The chemotactic receptor for human C5a anaphylatoxin. Nature. 1991 Feb 14;349(6310):614-7. [Article]
  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Gerard NP, Bao L, Xiao-Ping H, Eddy RL Jr, Shows TB, Gerard C: Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene. Biochemistry. 1993 Feb 9;32(5):1243-50. [Article]
  6. DeMartino JA, Van Riper G, Siciliano SJ, Molineaux CJ, Konteatis ZD, Rosen H, Springer MS: The amino terminus of the human C5a receptor is required for high affinity C5a binding and for receptor activation by C5a but not C5a analogs. J Biol Chem. 1994 May 20;269(20):14446-50. [Article]
  7. Monk PN, Barker MD, Partridge LJ, Pease JE: Mutation of glutamate 199 of the human C5a receptor defines a binding site for ligand distinct from the receptor N terminus. J Biol Chem. 1995 Jul 14;270(28):16625-9. [Article]
  8. Giannini E, Brouchon L, Boulay F: Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo. J Biol Chem. 1995 Aug 11;270(32):19166-72. [Article]
  9. Chen Z, Zhang X, Gonnella NC, Pellas TC, Boyar WC, Ni F: Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin. J Biol Chem. 1998 Apr 24;273(17):10411-9. [Article]
  10. Christophe T, Rabiet MJ, Tardif M, Milcent MD, Boulay F: Human complement 5a (C5a) anaphylatoxin receptor (CD88) phosphorylation sites and their specific role in receptor phosphorylation and attenuation of G protein-mediated responses. Desensitization of C5a receptor controls superoxide production but not receptor sequestration in HL-60 cells. J Biol Chem. 2000 Jan 21;275(3):1656-64. [Article]
  11. Farzan M, Schnitzler CE, Vasilieva N, Leung D, Kuhn J, Gerard C, Gerard NP, Choe H: Sulfated tyrosines contribute to the formation of the C5a docking site of the human C5a anaphylatoxin receptor. J Exp Med. 2001 May 7;193(9):1059-66. [Article]
  12. Braun L, Christophe T, Boulay F: Phosphorylation of key serine residues is required for internalization of the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin, dynamin, and clathrin-dependent pathway. J Biol Chem. 2003 Feb 7;278(6):4277-85. Epub 2002 Dec 2. [Article]
  13. Klco JM, Lassere TB, Baranski TJ: C5a receptor oligomerization. I. Disulfide trapping reveals oligomers and potential contact surfaces in a G protein-coupled receptor. J Biol Chem. 2003 Sep 12;278(37):35345-53. Epub 2003 Jun 30. [Article]
  14. Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ, van Kessel KP: Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol. 2004 Jun 1;172(11):6994-7001. [Article]
  15. Postma B, Kleibeuker W, Poppelier MJ, Boonstra M, Van Kessel KP, Van Strijp JA, de Haas CJ: Residues 10-18 within the C5a receptor N terminus compose a binding domain for chemotaxis inhibitory protein of Staphylococcus aureus. J Biol Chem. 2005 Jan 21;280(3):2020-7. Epub 2004 Nov 12. [Article]
  16. Liu ZJ, Yang YJ, Jiang L, Xu YC, Wang AX, Du GH, Gao JM: Tyrosine sulfation in N-terminal domain of human C5a receptor is necessary for binding of chemotaxis inhibitory protein of Staphylococcus aureus. Acta Pharmacol Sin. 2011 Aug;32(8):1038-44. doi: 10.1038/aps.2011.53. Epub 2011 Jun 27. [Article]
  17. Robertson N, Rappas M, Dore AS, Brown J, Bottegoni G, Koglin M, Cansfield J, Jazayeri A, Cooke RM, Marshall FH: Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727. Nature. 2018 Jan 3;553(7686):111-114. doi: 10.1038/nature25025. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB15011Avacopanapproved, investigationalyesantagonistDetails