CD88

C5a anaphylatoxin chemotactic receptor 1
other names	C5a anaphylatoxin chemotactic receptor, C5a-R, C5aR
Properties of human protein
Mass / length primary structure	350 amino acids , 39,336 Da
Identifier
External IDs	GeneCards : C5AR1 ; OMIM : 113995 ; UniProt : P21730 ;
	Orthologue (human)
Entrez	728
Ensemble	ENSG00000197405
UniProt	P21730
Refseq (mRNA)	NM_001736.3
Refseq (protein)	NP_001727.1
PubMed search	728

CD88 (synonymous C5a anaphylatoxin chemotactic receptor 1 , C5aR1) is a surface protein and participates in the complement system of the immune response .

properties

Schematic structure of CD88

CD88 is the receptor for the anaphylatoxin C5a and has two contact points for C5a. At the N terminus of CD88 there is a binding site with a comparatively high affinity and in the vicinity of the transmembrane domain of CD88 there is a binding site of lower affinity, which is responsible for the signal transduction of CD88 within the cell. Binding of C5a to CD88 leads to increased chemotaxis , increased degranulation , an increase in the cytosolic concentration of calcium ions and an increased formation of superoxide . It is involved in inflammation , ontogenesis and the development of obesity and cancer . CD88 is a G protein-coupled receptor with seven transmembrane domains (a heptahelical receptor ). CD88 is glycosylated , phosphorylated, and sulfated . CD88 is produced by different cell types, including granulocytes , monocytes , dendritic cells , astrocytes , and by the cell line HepG2 as well as macrophages and T cells .

Various agonists and antagonists for CD88 have been described.

Web links

MeSH CD88

Individual evidence

↑ Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ: The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury . In: The Journal of Neuroscience . 35, No. 16, April 2015, pp. 6517-31. doi : 10.1523 / JNEUROSCI.5218-14.2015 . PMID 25904802 .
↑ Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP: C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling . In: FASEB Journal . 27, No. 2, February 2013, pp. 822-31. doi : 10.1096 / fj.12-220582 . PMID 23118029 .
↑ Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, Coukos G, Lambris JD: Modulation of the antitumor immune response by complement . In: Nature Immunology . 9, No. 11, November 2008, pp. 1225-35. doi : 10.1038 / ni.1655 . PMID 18820683 . PMC 2678913 (free full text).
^ TM Woodruff, KS Nandakumar, F. Tedesco: Inhibiting the C5-C5a receptor axis. In: Molecular immunology. Volume 48, Number 14, August 2011, pp. 1631-1642, doi : 10.1016 / j.molimm.2011.04.014 , PMID 21549429 .
↑ C. Gerard, NP Gerard: C5A anaphylatoxin and its seven transmembrane-segment receptor. In: Annual review of immunology. Volume 12, 1994, pp. 775-808, doi : 10.1146 / annurev.iy.12.040194.004015 , PMID 8011297 .
^ Klos A, Wende E, Wareham KJ, Monk PN: International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors . In: Pharmacological Reviews . 65, No. 1, January 2013, pp. 500–43. doi : 10.1124 / pr.111.005223 . PMID 23383423 .
^ PN Monk, AM Scola, P. Madala, DP Fairlie: Function, structure and therapeutic potential of complement C5a receptors. In: British journal of pharmacology. Volume 152, Number 4, October 2007, pp. 429-448, doi : 10.1038 / sj.bjp.0707332 , PMID 17603557 , PMC 2050825 (free full text).
↑ Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP: Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a . In: Journal of Medicinal Chemistry . 41, No. 18, August 1998, pp. 3417-25. doi : 10.1021 / jm980065 . PMID 9719594 .
↑ Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W: Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists . In: Bioorganic & Medicinal Chemistry Letters . 18, No. 14, July 2008, pp. 3852-5. doi : 10.1016 / j.bmcl.2008.06.059 . PMID 18595693 .
↑ Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T, Ohbora T, Mishina T, Komatsu H, Naka Y: Identification of a potent and orally active non-peptide C5a receptor antagonist . In: The Journal of Biological Chemistry . 277, No. 51, December 2002, pp. 49403-7. doi : 10.1074 / jbc.M209672200 . PMID 12384495 .

[1] Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ: The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury . In: The Journal of Neuroscience . 35, No. 16, April 2015, pp. 6517-31. doi : 10.1523 / JNEUROSCI.5218-14.2015 . PMID 25904802 .

[2] Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP: C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling . In: FASEB Journal . 27, No. 2, February 2013, pp. 822-31. doi : 10.1096 / fj.12-220582 . PMID 23118029 .

[3] Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, Coukos G, Lambris JD: Modulation of the antitumor immune response by complement . In: Nature Immunology . 9, No. 11, November 2008, pp. 1225-35. doi : 10.1038 / ni.1655 . PMID 18820683 . PMC 2678913 (free full text).

[4] TM Woodruff, KS Nandakumar, F. Tedesco: Inhibiting the C5-C5a receptor axis. In: Molecular immunology. Volume 48, Number 14, August 2011, pp. 1631-1642, doi : 10.1016 / j.molimm.2011.04.014 , PMID 21549429 .

[5] C. Gerard, NP Gerard: C5A anaphylatoxin and its seven transmembrane-segment receptor. In: Annual review of immunology. Volume 12, 1994, pp. 775-808, doi : 10.1146 / annurev.iy.12.040194.004015 , PMID 8011297 .

[pmid=_23383423-6] Klos A, Wende E, Wareham KJ, Monk PN: International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors . In: Pharmacological Reviews . 65, No. 1, January 2013, pp. 500–43. doi : 10.1124 / pr.111.005223 . PMID 23383423 .

[7] PN Monk, AM Scola, P. Madala, DP Fairlie: Function, structure and therapeutic potential of complement C5a receptors. In: British journal of pharmacology. Volume 152, Number 4, October 2007, pp. 429-448, doi : 10.1038 / sj.bjp.0707332 , PMID 17603557 , PMC 2050825 (free full text).

[8] Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP: Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a . In: Journal of Medicinal Chemistry . 41, No. 18, August 1998, pp. 3417-25. doi : 10.1021 / jm980065 . PMID 9719594 .

[9] Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W: Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists . In: Bioorganic & Medicinal Chemistry Letters . 18, No. 14, July 2008, pp. 3852-5. doi : 10.1016 / j.bmcl.2008.06.059 . PMID 18595693 .

[10] Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T, Ohbora T, Mishina T, Komatsu H, Naka Y: Identification of a potent and orally active non-peptide C5a receptor antagonist . In: The Journal of Biological Chemistry . 277, No. 51, December 2002, pp. 49403-7. doi : 10.1074 / jbc.M209672200 . PMID 12384495 .