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advanced glycosylation end-product specific receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2843

Nomenclature: advanced glycosylation end-product specific receptor

Abbreviated Name: RAGE

Family: Immunoglobulin like domain containing proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 404 6p21.32 AGER advanced glycosylation end-product specific receptor 9
Mouse 1 402 17 B1 Ager advanced glycosylation end product-specific receptor
Rat 1 402 20p12 Ager advanced glycosylation end product-specific receptor
Gene and Protein Information Comments
The human mRNA undergoes extensive alternative splicing, generating many protein isoforms. We include the predominant isoform in the table above. Some isoforms lack the membrane spanning region and are known as soluble RAGE (sRAGE) and may act as decoy receptors for RAGE ligands. The mouse gene similarly produces several reported isoforms.
Previous and Unofficial Names Click here for help
advanced glycosylation end product-specific receptor
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
azeliragon Small molecule or natural product Primary target of this compound Hs Antagonist ~6.0 pIC50 7,10
pIC50 ~6.0 (IC50 ~1x10-6 M) [7,10]
Immunopharmacology Comments
RAGE is a single chain, membrane bound immunoglobulin type protein [9,11,19] which acts as a pattern recognition receptor for ligands containing a common glycation motif. In addition to advanced glycation endproducts, reported ligands include HMGB1 (amphoterin) [6], S100A7 (S100 calcium-binding protein A7 aka psoriasin) [8], S100B (S100 calcium-binding protein B) [14], amyloid β [5] and phosphatidylserine. RAGE has been linked to several chronic diseases, the pathogenesis of which are hypothesized to result from RAGE-induced activation of the NF-κB signalling pathway and subsequent modulation of pro-inflammatory genes [1]. RAGE modulation is an attractive mechanism being investigated by the pharmaceutical industry, for the development of novel therapies [2,4,13,17] for conditions including diabetes mellitus [3,16] and Alzheimer's disease (AD) [12,15,18].
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  Tissue repair

References

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1. Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, Hong M, Luther T, Henle T, Klöting I et al.. (2001) Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes, 50 (12): 2792-808. [PMID:11723063]

2. Bongarzone S, Savickas V, Luzi F, Gee AD. (2017) Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective. J Med Chem, 60 (17): 7213-7232. [PMID:28482155]

3. Hori O, Yan SD, Ogawa S, Kuwabara K, Matsumoto M, Stern D, Schmidt AM. (1996) The receptor for advanced glycation end-products has a central role in mediating the effects of advanced glycation end-products on the development of vascular disease in diabetes mellitus. Nephrol Dial Transplant, 11 Suppl 5: 13-6. [PMID:9044300]

4. Kim SH, Han YT. (2015) Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity. Arch Pharm Res, 38 (11): 1952-62. [PMID:25842360]

5. Lee JJ, Wang PW, Yang IH, Wu CL, Chuang JH. (2015) Amyloid-beta mediates the receptor of advanced glycation end product-induced pro-inflammatory response via toll-like receptor 4 signaling pathway in retinal ganglion cell line RGC-5. Int J Biochem Cell Biol, 64: 1-10. [PMID:25783987]

6. Liang Y, Hou C, Kong J, Wen H, Zheng X, Wu L, Huang H, Chen Y. (2015) HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2. Mol Cell Biochem, 405 (1-2): 63-71. [PMID:25862459]

7. Mjalli A, Andrews R, Shen J, Rothlein R. (2005) Rage antagonists as agents to reverse amyloidosis and diseases associated therewith. Patent number: US20050026811 A1. Assignee: Mjalli A, Andrews R, Shen J, Rothlein R. Priority date: 20/05/2003. Publication date: 03/02/2005.

8. Nasser MW, Wani NA, Ahirwar DK, Powell CA, Ravi J, Elbaz M, Zhao H, Padilla L, Zhang X, Shilo K et al.. (2015) RAGE Mediates S100A7-Induced Breast Cancer Growth and Metastasis by Modulating the Tumor Microenvironment. Cancer Res, 75 (6): 974-85. [PMID:25572331]

9. Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem, 267 (21): 14998-5004. [PMID:1378843]

10. Saito S, Ihara M. (2014) New therapeutic approaches for Alzheimer's disease and cerebral amyloid angiopathy. Front Aging Neurosci, 6: 290. [PMID:25368578]

11. Schmidt AM, Hori O, Cao R, Yan SD, Brett J, Wautier JL, Ogawa S, Kuwabara K, Matsumoto M, Stern D. (1996) RAGE: a novel cellular receptor for advanced glycation end products. Diabetes, 45 Suppl 3: S77-80. [PMID:8674899]

12. Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Münch G. (2011) Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease. Neurobiol Aging, 32 (5): 763-77. [PMID:19464758]

13. Tekabe Y, Anthony T, Li Q, Ray R, Rai V, Zhang G, Schmidt AM, Johnson LL. (2015) Treatment effect with anti-RAGE F(ab')2 antibody improves hind limb angiogenesis and blood flow in Type 1 diabetic mice with left femoral artery ligation. Vasc Med, 20 (3): 212-8. [PMID:25808570]

14. Villarreal A, Seoane R, González Torres A, Rosciszewski G, Angelo MF, Rossi A, Barker PA, Ramos AJ. (2014) S100B protein activates a RAGE-dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis. J Neurochem, 131 (2): 190-205. [PMID:24923428]

15. Walker D, Lue LF, Paul G, Patel A, Sabbagh MN. (2015) Receptor for advanced glycation endproduct modulators: a new therapeutic target in Alzheimer's disease. Expert Opin Investig Drugs, 24 (3): 393-9. [PMID:25586103]

16. Wendt T, Harja E, Bucciarelli L, Qu W, Lu Y, Rong LL, Jenkins DG, Stein G, Schmidt AM, Yan SF. (2006) RAGE modulates vascular inflammation and atherosclerosis in a murine model of type 2 diabetes. Atherosclerosis, 185 (1): 70-7. [PMID:16076470]

17. Xia JR, Chen TT, Li WD, Lu FL, Liu J, Cai XG, Lu Q, Yang CP. (2015) Inhibitory effect of receptor for advanced glycation end product‑specific small interfering RNAs on the development of hepatic fibrosis in primary rat hepatic stellate cells. Mol Med Rep, 12 (1): 569-74. [PMID:25673150]

18. Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J et al.. (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature, 382 (6593): 685-91. [PMID:8751438]

19. Yan SD, Stern D, Schmidt AM. (1997) What's the RAGE? The receptor for advanced glycation end products (RAGE) and the dark side of glucose. Eur J Clin Invest, 27 (3): 179-81. [PMID:9088851]

How to cite this page

Immunoglobulin like domain containing proteins: advanced glycosylation end-product specific receptor. Last modified on 30/01/2018. Accessed on 14/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2843.