Receptor de C5a

C5AR1
Estruturas dispoñibles
PDB	Buscar ortólogos: PDBe, RCSB
Identificadores
Nomenclatura	Outros nomes C5AR1, C5A, C5AR, C5R1, CD88, receptor do compoñente do complemento 5a 1, receptor de C5a, receptor do complemento C5a 1 ;
Identificadores; externos	OMIM: 113995 ; MGI: 88232 ; HomoloGene: 20413 ; EBI: C5AR1 ; GeneCards: Xene C5AR1 ; UniProt: C5AR1 ;
Locus	Cr. 19 q13.32
Ontoloxía Xénica	Referencias: AmiGO / QuickGO
	Referencias: AmiGO / QuickGO
Padrón de expresión de ARNm
	Máis información
Ortólogos
Especies
Humano	Rato
Entrez
728	12273
Ensembl
Véxase HS	Véxase MM
UniProt
P21730	P30993
RefSeq; (ARNm)
NM_001736	NM_001173550
RefSeq; (proteína) NCBI
NP_001727	NP_001167021
Localización (UCSC)
Cr. 19:; 47.29 – 47.32 Mb	Cr. 7:; 15.98 – 15.99 Mb
PubMed (Busca)
728 ;	12273

O receptor de C5a (C5aR), tamén coñecido como receptor do compoñente do complemento 5a 1 (C5AR1) ou CD88 (Cluster de Diferenciación 88), é un receptor acoplado á proteína G para o C5a. Funciona como receptor do complemento.^[1] O receptor de C5a modula as respostas inflamatorias, a obesidade, o desenvolvemento e os cancros.^[2]^[3]^[4] Desde un punto de vista da transdución de sinais, a activación do receptor de C5a está implicada no recrutamento da β-arrestina2 a través de Rab5a,^[5] o acoplamento de proteínas Gαi,^[6] a fosforilación de ERK1/2, ^[7] a mobilización de calcio e a activación de Rho,^[8] o que leva ás funcións augas abaixo, como a secreción de citocinas, a quimiotaxe e a fagocitose.

Células

O receptor de C5a exprésase en:^[9]

Agonistas e antagonistas

Desenvolvéronse agonistas e antagonistas potentes e selectivos para o receptor de C5a.^[10]^[11]^[12]^[13]^[14]^[15]

Notas

↑ Gerard C, Gerard NP (1994). "C5A anaphylatoxin and its seven transmembrane-segment receptor". Annual Review of Immunology 12: 775–808. PMID 8011297. doi:10.1146/annurev.iy.12.040194.004015.
↑ Brennan FH, Gordon R, Lao HW, Biggins PJ, Taylor SM, Franklin RJ, Woodruff TM, Ruitenberg MJ (abril de 2015). "The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury". The Journal of Neuroscience 35 (16): 6517–6531. PMC 6605214. PMID 25904802. doi:10.1523/JNEUROSCI.5218-14.2015.
↑ Lim J, Iyer A, Suen JY, Seow V, Reid RC, Brown L, Fairlie DP (febreiro de 2013). "C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling". FASEB Journal 27 (2): 822–831. PMID 23118029. doi:10.1096/fj.12-220582.
↑ Markiewski MM, DeAngelis RA, Benencia F, Ricklin-Lichtsteiner SK, Koutoulaki A, Gerard C, Coukos G, Lambris JD (novembro de 2008). "Modulation of the antitumor immune response by complement". Nature Immunology 9 (11): 1225–1235. PMC 2678913. PMID 18820683. doi:10.1038/ni.1655.
↑ Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J (marzo de 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. PMC 10105068. PMID 36882040. doi:10.1159/000530012.
↑ Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, Tian X, Wang B, Bin Y, Chen P, Yan W, Fu P, Shao Z (abril de 2023). "Mechanism of activation and biased signaling in complement receptor C5aR1". Cell Research 33 (4): 312–324. PMC 9937529. PMID 36806352. doi:10.1038/s41422-023-00779-2.
↑ Li XX, Lee JD, Massey NL, Guan C, Robertson AA, Clark RJ, Woodruff TM (outubro de 2020). "Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function". Biochemical Pharmacology 180: 114156. PMID 32682759. doi:10.1016/j.bcp.2020.114156.
↑ Wang X, Iyer A, Lyons AB, Körner H, Wei W (2019). "Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages". Frontiers in Immunology 10: 2031. PMC 6718513. PMID 31507616. doi:10.3389/fimmu.2019.02031.
↑ Klos A, Wende E, Wareham KJ, Monk PN (xaneiro de 2013). "International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews 65 (1): 500–543. PMID 23383423. doi:10.1124/pr.111.005223.
↑ Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ (novembro de 2021). "Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity". Journal of Medicinal Chemistry 64 (22): 16598–16608. PMID 34762432. doi:10.1021/acs.jmedchem.1c01174.
↑ Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP (agosto de 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. PMID 9719594. doi:10.1021/jm9800651.
↑ Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W (xullo de 2008). "Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists". Bioorganic & Medicinal Chemistry Letters 18 (14): 3852–3855. PMID 18595693. doi:10.1016/j.bmcl.2008.06.059.
↑ 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 (decembro de 2002). "Identification of a potent and orally active non-peptide C5a receptor antagonist". The Journal of Biological Chemistry 277 (51): 49403–49407. PMID 12384495. doi:10.1074/jbc.M209672200.
↑ Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP (abril de 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. PMC 4837355. PMID 27094554. doi:10.1038/srep24575.
↑ Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (maio de 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. PMID 10799917. doi:10.4049/jimmunol.164.10.5492.

Véxase tamén

Outros artigos

C5a para o mecanismo de unión
Receptor de C3a
Receptor do complemento

Bibliografía

Sengeløv H (1996). "Complement receptors in neutrophils". Critical Reviews in Immunology 15 (2): 107–131. PMID 8573284. doi:10.1615/critrevimmunol.v15.i2.10.
Beil WJ, Schulz M, Wefelmeyer U (xullo de 2000). "Mast cell granule composition and tissue location--a close correlation". Histology and Histopathology 15 (3): 937–946. PMID 10963136.
Yamamoto T (xaneiro de 2007). "Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes". Pathology International 57 (1): 1–11. PMID 17199736. doi:10.1111/j.1440-1827.2007.02049.x.
Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (xuño de 1992). "Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19". Genomics 13 (2): 437–440. PMID 1612600. doi:10.1016/0888-7543(92)90265-T.
Gerard NP, Gerard C (febreiro de 1991). "The chemotactic receptor for human C5a anaphylatoxin". Nature 349 (6310): 614–617. Bibcode:1991Natur.349..614G. PMID 1847994. doi:10.1038/349614a0.
Boulay F, Mery L, Tardif M, Brouchon L, Vignais P (marzo de 1991). "Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cells". Biochemistry 30 (12): 2993–2999. PMID 2007135. doi:10.1021/bi00226a002.
Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, Arthur LO, Farrar WL, Wahl LM (maio de 1989). "HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes". Journal of Immunology 142 (10): 3553–3559. PMID 2541200. doi:10.4049/jimmunol.142.10.3553.
Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ, Glovsky MM, Eddy SM, Ward PA (setembro de 1994). "C5a-induced expression of P-selectin in endothelial cells". The Journal of Clinical Investigation 94 (3): 1147–1155. PMC 295185. PMID 7521884. doi:10.1172/JCI117430.
Giannini E, Brouchon L, Boulay F (agosto de 1995). "Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo". The Journal of Biological Chemistry 270 (32): 19166–19172. PMID 7642584. doi:10.1074/jbc.270.32.19166.
Buhl AM, Osawa S, Johnson GL (agosto de 1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor". The Journal of Biological Chemistry 270 (34): 19828–19832. PMID 7649993. doi:10.1074/jbc.270.34.19828.
Wennogle LP, Conder L, Winter C, Braunwalder A, Vlattas S, Kramer R, Cioffi C, Hu SI (xullo de 1994). "Stabilization of C5a receptor--G-protein interactions through ligand binding". Journal of Cellular Biochemistry 55 (3): 380–388. PMID 7962171. doi:10.1002/jcb.240550316.
Gerard NP, Bao L, Xiao-Ping H, Eddy RL, Shows TB, Gerard C (febreiro de 1993). "Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene". Biochemistry 32 (5): 1243–1250. PMID 8383526. doi:10.1021/bi00056a007.
Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C (agosto de 1996). "Molecular cloning and characterization of the human anaphylatoxin C3a receptor". The Journal of Biological Chemistry 271 (34): 20231–20234. PMID 8702752. doi:10.1074/jbc.271.34.20231.
Werfel T, Zwirner J, Oppermann M, Sieber A, Begemann G, Drommer W, Kapp A, Götze O (agosto de 1996). "CD88 antibodies specifically bind to C5aR on dermal CD117+ and CD14+ cells and react with a desmosomal antigen in human skin". Journal of Immunology 157 (4): 1729–1735. PMID 8759762. doi:10.4049/jimmunol.157.4.1729.
Höpken UE, Lu B, Gerard NP, Gerard C (September 1996). "The C5a chemoattractant receptor mediates mucosal defence to infection". Nature 383 (6595): 86–89. Bibcode:1996Natur.383...86H. PMID 8779720. doi:10.1038/383086a0.
Chen Z, Zhang X, Gonnella NC, Pellas TC, Boyar WC, Ni F (abril de 1998). "Residues 21-30 within the extracellular N-terminal region of the C5a receptor represent a binding domain for the C5a anaphylatoxin". The Journal of Biological Chemistry 273 (17): 10411–10419. PMID 9553099. doi:10.1074/jbc.273.17.10411.
Floreani AA, Heires AJ, Welniak LA, Miller-Lindholm A, Clark-Pierce L, Rennard SI, Morgan EL, Sanderson SD (maio de 1998). "Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke". Journal of Immunology 160 (10): 5073–5081. PMID 9590258. doi:10.4049/jimmunol.160.10.5073.
Ottonello L, Corcione A, Tortolina G, Airoldi I, Albesiano E, Favre A, D'Agostino R, Malavasi F, Pistoia V, Dallegri F (xuño de 1999). "rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues". Journal of Immunology 162 (11): 6510–6517. PMID 10352266. doi:10.4049/jimmunol.162.11.6510.
Kohleisen B, Shumay E, Sutter G, Foerster R, Brack-Werner R, Nuesse M, Erfle V (decembro de 1999). "Stable expression of HIV-1 Nef induces changes in growth properties and activation state of human astrocytes". AIDS 13 (17): 2331–2341. PMID 10597774. doi:10.1097/00002030-199912030-00004.
Monk PN, Scola AM, Madala P, Fairlie DP (outubro de 2007). "Function, structure and therapeutic potential of complement C5a receptors". British Journal of Pharmacology 152 (4): 429–448. PMC 2050825. PMID 17603557. doi:10.1038/sj.bjp.0707332.

Ligazóns externos

"Anaphylatoxin Receptors: C5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arquivado dende o orixinal o 2014-04-07. Consultado o 2007-10-25.
C5a receptors Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.
Localización no xenoma humano de C5AR1 e páxina con detalles sobre o xene C5AR1 no UCSC Genome Browser.
Relación de toda a información estrutural dispoñible en PDB para UniProt: P21730 (C5a anaphylatoxin chemotactic receptor 1) en PDBe-KB.

[pmid8011297-1] Gerard C, Gerard NP (1994). "C5A anaphylatoxin and its seven transmembrane-segment receptor". Annual Review of Immunology 12: 775–808. PMID 8011297. doi:10.1146/annurev.iy.12.040194.004015.

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

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

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

[5] Wu KC, Condon ND, Hill TA, Reid RC, Fairlie D, Lim J (marzo de 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. PMC 10105068. PMID 36882040. doi:10.1159/000530012.

[6] Feng Y, Zhao C, Deng Y, Wang H, Ma L, Liu S, Tian X, Wang B, Bin Y, Chen P, Yan W, Fu P, Shao Z (abril de 2023). "Mechanism of activation and biased signaling in complement receptor C5aR1". Cell Research 33 (4): 312–324. PMC 9937529. PMID 36806352. doi:10.1038/s41422-023-00779-2.

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

[8] Wang X, Iyer A, Lyons AB, Körner H, Wei W (2019). "Emerging Roles for G-protein Coupled Receptors in Development and Activation of Macrophages". Frontiers in Immunology 10: 2031. PMC 6718513. PMID 31507616. doi:10.3389/fimmu.2019.02031.

[pmid=_23383423-9] Klos A, Wende E, Wareham KJ, Monk PN (xaneiro de 2013). "International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacological Reviews 65 (1): 500–543. PMID 23383423. doi:10.1124/pr.111.005223.

[10] Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ (novembro de 2021). "Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity". Journal of Medicinal Chemistry 64 (22): 16598–16608. PMID 34762432. doi:10.1021/acs.jmedchem.1c01174.

[11] Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP (agosto de 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. PMID 9719594. doi:10.1021/jm9800651.

[12] Gong Y, Barbay JK, Buntinx M, Li J, Wauwe JV, Claes C, Lommen GV, Hornby PJ, He W (xullo de 2008). "Design and optimization of aniline-substituted tetrahydroquinoline C5a receptor antagonists". Bioorganic & Medicinal Chemistry Letters 18 (14): 3852–3855. PMID 18595693. doi:10.1016/j.bmcl.2008.06.059.

[13] 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 (decembro de 2002). "Identification of a potent and orally active non-peptide C5a receptor antagonist". The Journal of Biological Chemistry 277 (51): 49403–49407. PMID 12384495. doi:10.1074/jbc.M209672200.

[14] Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP (abril de 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. PMC 4837355. PMID 27094554. doi:10.1038/srep24575.

[15] Ulrich JT, Cieplak W, Paczkowski NJ, Taylor SM, Sanderson SD (maio de 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. PMID 10799917. doi:10.4049/jimmunol.164.10.5492.

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