advanced glycosylation end-product specific receptor | Immunoglobulin like domain containing proteins | IUPHAR/BPS Guide to PHARMACOLOGY

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advanced glycosylation end-product specific receptor

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

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 404 6p21.3 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
advanced glycosylation end product-specific receptor
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
azeliragon 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
GO Annotations:  Associated to 1 GO processes
GO:0005044 scavenger receptor activity TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 6 GO processes
GO:0006954 inflammatory response TAS
GO:0045087 innate immune response TAS
GO:0061890 positive regulation of astrocyte activation IGI
GO:1903980 positive regulation of microglial cell activation IGI
GO:2000439 positive regulation of monocyte extravasation IMP
click arrow to show/hide IEA associations
GO:1904597 negative regulation of connective tissue replacement involved in inflammatory response wound healing IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0001914 regulation of T cell mediated cytotoxicity IDA
GO:0042104 positive regulation of activated T cell proliferation IMP
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation IDA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0001914 regulation of T cell mediated cytotoxicity IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 8 GO processes
GO:0001914 regulation of T cell mediated cytotoxicity IDA
GO:0042104 positive regulation of activated T cell proliferation IMP
GO:0061890 positive regulation of astrocyte activation IGI
GO:1903980 positive regulation of microglial cell activation IGI
GO:2000439 positive regulation of monocyte extravasation IMP
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation IDA
GO:2001200 positive regulation of dendritic cell differentiation IMP
click arrow to show/hide IEA associations
GO:1904597 negative regulation of connective tissue replacement involved in inflammatory response wound healing IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:2001200 positive regulation of dendritic cell differentiation IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 8 GO processes
GO:0032693 negative regulation of interleukin-10 production IDA
GO:0032735 positive regulation of interleukin-12 production IMP
GO:0042535 positive regulation of tumor necrosis factor biosynthetic process ISS
GO:0045080 positive regulation of chemokine biosynthetic process ISS
GO:0045410 positive regulation of interleukin-6 biosynthetic process ISS
GO:0050725 positive regulation of interleukin-1 beta biosynthetic process ISS
GO:1904472 positive regulation of endothelin secretion ISS
click arrow to show/hide IEA associations
GO:0071639 positive regulation of monocyte chemotactic protein-1 production IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 4 GO processes
GO:0042104 positive regulation of activated T cell proliferation IMP
GO:0045080 positive regulation of chemokine biosynthetic process ISS
GO:2000439 positive regulation of monocyte extravasation IMP
click arrow to show/hide IEA associations
GO:0071639 positive regulation of monocyte chemotactic protein-1 production IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0042104 positive regulation of activated T cell proliferation IMP
GO:1903980 positive regulation of microglial cell activation IGI
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation IDA
Immuno Process:  Tissue repair
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1904597 negative regulation of connective tissue replacement involved in inflammatory response wound healing IEA

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 19/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2843.