Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP1Q82J)

DOT Name C5a anaphylatoxin chemotactic receptor 2 (C5AR2)
Synonyms Complement component 5a receptor 2; G-protein coupled receptor 77
Gene Name C5AR2
Related Disease
Melanoma ( )
Advanced cancer ( )
Bullous pemphigoid ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Dermatitis ( )
Familial Mediterranean fever ( )
G6PD deficiency ( )
Hidradenitis suppurativa ( )
Hyperlipidemia, familial combined, LPL related ( )
Lung cancer ( )
Lung carcinoma ( )
Meningococcal disease ( )
Meningococcemia ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Retinitis pigmentosa ( )
Tuberculosis ( )
Arthritis ( )
Dental caries ( )
Hyperlipidemia ( )
Inflammation ( )
Renal fibrosis ( )
UniProt ID
C5AR2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00001
Sequence
MGNDSVSYEYGDYSDLSDRPVDCLDGACLAIDPLRVAPLPLYAAIFLVGVPGNAMVAWVA
GKVARRRVGATWLLHLAVADLLCCLSLPILAVPIARGGHWPYGAVGCRALPSIILLTMYA
SVLLLAALSADLCFLALGPAWWSTVQRACGVQVACGAAWTLALLLTVPSAIYRRLHQEHF
PARLQCVVDYGGSSSTENAVTAIRFLFGFLGPLVAVASCHSALLCWAARRCRPLGTAIVV
GFFVCWAPYHLLGLVLTVAAPNSALLARALRAEPLIVGLALAHSCLNPMLFLYFGRAQLR
RSLPAACHWALRESQGQDESVDSKKSTSHDLVSEMEV
Function
Receptor for the chemotactic and inflammatory C3a, C4a and C5a anaphylatoxin peptides and also for their dearginated forms ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to G(i)-mediated signaling pathways.
Tissue Specificity Frontal cortex, hippocampus, hypothalamus, pons and liver.
Reactome Pathway
Regulation of Complement cascade (R-HSA-977606 )
Peptide ligand-binding receptors (R-HSA-375276 )

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Melanoma DIS1RRCY Definitive Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Bullous pemphigoid DISOJLKV Strong Biomarker [3]
Coronary atherosclerosis DISKNDYU Strong Genetic Variation [4]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [4]
Dermatitis DISY5SZC Strong Biomarker [3]
Familial Mediterranean fever DISVP5WP Strong Posttranslational Modification [5]
G6PD deficiency DISYF1GO Strong Genetic Variation [6]
Hidradenitis suppurativa DIS3ZNAK Strong Biomarker [7]
Hyperlipidemia, familial combined, LPL related DISL1CE3 Strong Genetic Variation [8]
Lung cancer DISCM4YA Strong Biomarker [9]
Lung carcinoma DISTR26C Strong Biomarker [9]
Meningococcal disease DISGDM2Z Strong Biomarker [10]
Meningococcemia DIS33W79 Strong Biomarker [10]
Neoplasm DISZKGEW Strong Biomarker [9]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [11]
Retinitis pigmentosa DISCGPY8 Strong Genetic Variation [12]
Tuberculosis DIS2YIMD Strong Biomarker [13]
Arthritis DIST1YEL Limited Biomarker [14]
Dental caries DISRBCMD Limited Biomarker [15]
Hyperlipidemia DIS61J3S Limited Genetic Variation [12]
Inflammation DISJUQ5T Limited Biomarker [16]
Renal fibrosis DISMHI3I Limited Altered Expression [17]
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⏷ Show the Full List of 23 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [23]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [24]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [19]
Estradiol DMUNTE3 Approved Estradiol increases the expression of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [20]
Quercetin DM3NC4M Approved Quercetin increases the expression of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [21]
Obeticholic acid DM3Q1SM Approved Obeticholic acid decreases the expression of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [22]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of C5a anaphylatoxin chemotactic receptor 2 (C5AR2). [25]
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References

1 C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma.FASEB J. 2019 Oct;33(10):11060-11071. doi: 10.1096/fj.201800980RR. Epub 2019 Jul 12.
2 CD10(+)GPR77(+) Cancer-Associated Fibroblasts Promote Chemoresistance.Cancer Discov. 2018 Mar;8(3):264. doi: 10.1158/2159-8290.CD-RW2018-019. Epub 2018 Feb 2.
3 Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be Mitigated by C5aR2.Front Immunol. 2018 Mar 15;9:488. doi: 10.3389/fimmu.2018.00488. eCollection 2018.
4 Association of C5L2 genetic polymorphisms with coronary artery disease in a Han population in Xinjiang, China.Oncotarget. 2017 Jan 31;8(5):8590-8596. doi: 10.18632/oncotarget.14353.
5 Genetic analysis of C5a receptors in neutrophils from patients with familial Mediterranean fever.Mol Biol Rep. 2012 May;39(5):5503-10. doi: 10.1007/s11033-011-1353-6. Epub 2011 Dec 21.
6 Genetic polymorphisms in paraoxonase 1 and G protein-coupled receptor 77, and the risk of glucose-6-phosphate dehydrogenase deficiency in a Saudi population.Saudi Med J. 2015 May;36(5):544-8. doi: 10.15537/smj.2015.5.11860.
7 Integrating complement into the molecular pathogenesis of Hidradenitis Suppurativa.Exp Dermatol. 2020 Jan;29(1):86-92. doi: 10.1111/exd.14056. Epub 2019 Nov 29.
8 S323I polymorphism of the C5L2 gene was not identified in a Chinese population with familial combined hyperlipidemia or with type 2 diabetes.Genet Mol Res. 2011 Dec 22;10(4):3256-66. doi: 10.4238/2011.December.22.4.
9 CD10(+)GPR77(+) Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness.Cell. 2018 Feb 8;172(4):841-856.e16. doi: 10.1016/j.cell.2018.01.009. Epub 2018 Jan 25.
10 Distinct roles of the anaphylatoxin receptors C3aR, C5aR1 and C5aR2 in experimental meningococcal infections.Virulence. 2019 Dec;10(1):677-694. doi: 10.1080/21505594.2019.1640035.
11 Circulating C5L2 gene polymorphism is associated with type 2 diabetes mellitus in Saudi population.Mol Biol Rep. 2013 Nov;40(11):6323-7. doi: 10.1007/s11033-013-2745-6.
12 A novel mutation in C5L2 gene was associated with hyperlipidemia and retinitis pigmentosa in a Chinese family.Lipids Health Dis. 2014 May 6;13:75. doi: 10.1186/1476-511X-13-75.
13 C5aR contributes to the weak Th1 profile induced by an outbreak strain of Mycobacterium tuberculosis.Tuberculosis (Edinb). 2017 Mar;103:16-23. doi: 10.1016/j.tube.2016.12.005. Epub 2016 Dec 21.
14 Igniting the flame in arthritis: C5aR2 controls endothelial transcytosis of C5a.Sci Immunol. 2019 May 10;4(35):eaax0352. doi: 10.1126/sciimmunol.aax0352.
15 C5L2 Receptor Represses Brain-Derived Neurotrophic Factor Secretion in Lipoteichoic Acid-Stimulated Pulp Fibroblasts.J Dent Res. 2017 Jan;96(1):92-99. doi: 10.1177/0022034516673832. Epub 2016 Oct 8.
16 C5L2: a controversial receptor of complement anaphylatoxin, C5a.FASEB J. 2013 Mar;27(3):855-64. doi: 10.1096/fj.12-220509. Epub 2012 Dec 13.
17 Complement C5a receptors C5L2 and C5aR in renal fibrosis.Am J Physiol Renal Physiol. 2018 Jan 1;314(1):F35-F46. doi: 10.1152/ajprenal.00060.2017. Epub 2017 Sep 13.
18 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
19 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
20 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
21 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
22 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
23 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
24 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
25 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.