C5a receptor

C5AR1
Identifiers
Aliases	C5AR1, C5A, C5AR, C5R1, CD88, complement component 5a receptor 1, C5a receptor, complement C5a receptor 1
External IDs	OMIM: 113995 MGI: 88232 HomoloGene: 20413 GeneCards: C5AR1
Gene location (Human)
Chr.	Chromosome 19 (human)[1]
End	47,322,066 bp[1]
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)[2]
End	15,993,465 bp[2]
RNA expression pattern
	Top expressed in
	blood; ; monocyte; ; bone marrow; ; bone marrow cells; ; pituitary gland; ; right lung; ; anterior pituitary; ; periodontal fiber; ; upper lobe of left lung; ; right uterine tube;
	Top expressed in
	aortic valve; ; ascending aorta; ; blood; ; ankle; ; right lung lobe; ; submandibular gland; ; optic vesicle; ; subcutaneous adipose tissue; ; white adipose tissue; ; calvaria;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	complement component C5a binding; signal transducer activity; complement receptor activity; complement component C5a receptor activity; G protein-coupled receptor activity;
Cellular component	integral component of membrane; membrane; plasma membrane; apical part of cell; integral component of plasma membrane; cell surface; basolateral plasma membrane; cytoplasmic vesicle; secretory granule membrane;
Biological process	negative regulation of neuron apoptotic process; positive regulation of epithelial cell proliferation; mRNA transcription by RNA polymerase II; activation of phospholipase C activity; neutrophil chemotaxis; positive regulation of angiogenesis; chemotaxis; cellular defense response; response to lipopolysaccharide; animal organ regeneration; immune response; response to peptidoglycan; positive regulation of ERK1 and ERK2 cascade; positive regulation of neutrophil chemotaxis; complement receptor mediated signaling pathway; sensory perception of chemical stimulus; positive regulation of vascular endothelial growth factor production; cell proliferation in hindbrain; positive regulation of macrophage chemotaxis; signal transduction; defense response to Gram-positive bacterium; apoptotic process; regulation of complement activation; inflammatory response; phospholipase C-activating G protein-coupled receptor signaling pathway; neutrophil degranulation; leukocyte migration; cell chemotaxis; positive regulation of cytosolic calcium ion concentration; G protein-coupled receptor signaling pathway; complement component C5a signaling pathway; cognition; regulation of astrocyte activation; presynapse organization; regulation of amyloid-beta clearance; regulation of tau-protein kinase activity; regulation of microglial cell activation;
	Sources:Amigo / QuickGO
Orthologs
	728
	12273
	ENSG00000197405
	ENSMUSG00000049130
	P21730
	P30993
	NM_001736
	NM_001173550; NM_007577
	NP_001727
	NP_001167021; NP_031603
	Wikidata
View/Edit Human	View/Edit Mouse

The C5a receptor also known as complement component 5a receptor 1 (C5AR1) or CD88 (Cluster of Differentiation 88) is a G protein-coupled receptor for C5a. It functions as a complement receptor.[5] C5a receptor 1 modulates inflammatory responses, obesity, development and cancers.[6][7][8] From a signaling transduction perspective, C5a receptor 1 activation is implicated in β-arrestin2 recruitment via Rab5a,[9] coupling of Gαi proteins,[10] ERK1/2 phosphorylation, [11] calcium mobilization and Rho activation[12] leading to downstream functions, such as secretion of cytokines, chemotaxis, and phagocytosis.

C5a receptor structure and its residues possessing role in ligand binding or signaling.

Cells

The C5a receptor 1 is expressed on:[13]

Agonist and antagonists

Potent and selective agonist and antagonists for C5a receptor 1 have been developed.[14][15][16][17][18][19]

References

GRCh38: Ensembl release 89: ENSG00000197405 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000049130 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Gerard C, Gerard NP (1994). "C5A anaphylatoxin and its seven transmembrane-segment receptor". Annual Review of Immunology. 12: 775–808. doi:10.1146/annurev.iy.12.040194.004015. PMID 8011297.
Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, et al. (April 2015). "The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury". The Journal of Neuroscience. 35 (16): 6517–6531. doi:10.1523/JNEUROSCI.5218-14.2015. PMC 6605214. PMID 25904802.
Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP (February 2013). "C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling". FASEB Journal. 27 (2): 822–831. doi:10.1096/fj.12-220582. PMID 23118029. S2CID 25562647.
Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. (November 2008). "Modulation of the antitumor immune response by complement". Nature Immunology. 9 (11): 1225–1235. doi:10.1038/ni.1655. PMC 2678913. PMID 18820683.
Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J (March 2023). "Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages". Journal of Innate Immunity. 15 (1): 468–484. doi:10.1159/000530012. PMC 10105068. PMID 36882040.
Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, et al. (April 2023). "Mechanism of activation and biased signaling in complement receptor C5aR1". Cell Research. 33 (4): 312–324. doi:10.1038/s41422-023-00779-2. PMC 9937529. PMID 36806352.
Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, Woodruff TM (October 2020). "Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function". Biochemical Pharmacology. 180: 114156. doi:10.1016/j.bcp.2020.114156. PMID 32682759. S2CID 220653568.
Wang, Xinming; Iyer, Abishek; Lyons, A. Bruce; Körner, Heinrich; Wei, Wei (2019). "Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages". Frontiers in Immunology. 10: 2031. doi:10.3389/fimmu.2019.02031. ISSN 1664-3224. PMC 6718513. PMID 31507616.
Klos A, Wende E, Wareham KJ, Monk PN (January 2013). "International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500–543. doi:10.1124/pr.111.005223. PMID 23383423.
Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, et al. (November 2021). "Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity". Journal of Medicinal Chemistry. 64 (22): 16598–16608. doi:10.1021/acs.jmedchem.1c01174. PMID 34762432. S2CID 244040645.
Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP (August 1998). "Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a". Journal of Medicinal Chemistry. 41 (18): 3417–3425. doi:10.1021/jm9800651. PMID 9719594.
Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, et al. (July 2008). "Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (14): 3852–3855. doi:10.1016/j.bmcl.2008.06.059. PMID 18595693.
Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, et al. (December 2002). "Identification of a potent and orally active non-peptide C5a receptor antagonist". The Journal of Biological Chemistry. 277 (51): 49403–49407. doi:10.1074/jbc.M209672200. PMID 12384495.
Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, et al. (April 2016). "Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists". Scientific Reports. 6 (1): 24575. Bibcode:2016NatSR...624575S. doi:10.1038/srep24575. PMC 4837355. PMID 27094554.
Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (May 2000). "Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant". Journal of Immunology. 164 (10): 5492–5498. doi:10.4049/jimmunol.164.10.5492. PMID 10799917. S2CID 38942679.

External links

"Anaphylatoxin Receptors: C5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
C5a+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Human C5AR1 genome location and C5AR1 gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: P21730 (C5a anaphylatoxin chemotactic receptor 1) at the PDBe-KB.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000197405 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000049130 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8011297-5] Gerard C, Gerard NP (1994). "C5A anaphylatoxin and its seven transmembrane-segment receptor". Annual Review of Immunology. 12: 775–808. doi:10.1146/annurev.iy.12.040194.004015. PMID 8011297.

[6] Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, et al. (April 2015). "The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury". The Journal of Neuroscience. 35 (16): 6517–6531. doi:10.1523/JNEUROSCI.5218-14.2015. PMC 6605214. PMID 25904802.

[7] Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP (February 2013). "C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling". FASEB Journal. 27 (2): 822–831. doi:10.1096/fj.12-220582. PMID 23118029. S2CID 25562647.

[8] Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, et al. (November 2008). "Modulation of the antitumor immune response by complement". Nature Immunology. 9 (11): 1225–1235. doi:10.1038/ni.1655. PMC 2678913. PMID 18820683.

[9] Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J (March 2023). "Ras related protein Rab5a regulates complement C5a receptor trafficking, chemotaxis and chemokine secretion in human macrophages". Journal of Innate Immunity. 15 (1): 468–484. doi:10.1159/000530012. PMC 10105068. PMID 36882040.

[10] Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, et al. (April 2023). "Mechanism of activation and biased signaling in complement receptor C5aR1". Cell Research. 33 (4): 312–324. doi:10.1038/s41422-023-00779-2. PMC 9937529. PMID 36806352.

[11] Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, Woodruff TM (October 2020). "Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function". Biochemical Pharmacology. 180: 114156. doi:10.1016/j.bcp.2020.114156. PMID 32682759. S2CID 220653568.

[12] Wang, Xinming; Iyer, Abishek; Lyons, A. Bruce; Körner, Heinrich; Wei, Wei (2019). "Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages". Frontiers in Immunology. 10: 2031. doi:10.3389/fimmu.2019.02031. ISSN 1664-3224. PMC 6718513. PMID 31507616.

[pmid=_23383423-13] Klos A, Wende E, Wareham KJ, Monk PN (January 2013). "International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews. 65 (1): 500–543. doi:10.1124/pr.111.005223. PMID 23383423.

[14] Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, et al. (November 2021). "Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity". Journal of Medicinal Chemistry. 64 (22): 16598–16608. doi:10.1021/acs.jmedchem.1c01174. PMID 34762432. S2CID 244040645.

[15] Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP (August 1998). "Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a". Journal of Medicinal Chemistry. 41 (18): 3417–3425. doi:10.1021/jm9800651. PMID 9719594.

[16] Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, et al. (July 2008). "Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (14): 3852–3855. doi:10.1016/j.bmcl.2008.06.059. PMID 18595693.

[17] Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, et al. (December 2002). "Identification of a potent and orally active non-peptide C5a receptor antagonist". The Journal of Biological Chemistry. 277 (51): 49403–49407. doi:10.1074/jbc.M209672200. PMID 12384495.

[18] Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, et al. (April 2016). "Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists". Scientific Reports. 6 (1): 24575. Bibcode:2016NatSR...624575S. doi:10.1038/srep24575. PMC 4837355. PMID 27094554.

[19] Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (May 2000). "Induction of an antigen-specific CTL response by a conformationally biased agonist of human C5a anaphylatoxin as a molecular adjuvant". Journal of Immunology. 164 (10): 5492–5498. doi:10.4049/jimmunol.164.10.5492. PMID 10799917. S2CID 38942679.

Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

C5a receptor

Cells

Agonist and antagonists

See also

References

Further reading

External links