Advanced glycosylation end product-specific receptor (AGER)
The protein contains 404 amino acids for an estimated molecular weight of 42803 Da.
Mediates interactions of advanced glycosylation end products (AGE). These are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. Acts as a mediator of both acute and chronic vascular inflammation in conditions such as atherosclerosis and in particular as a complication of diabetes. AGE/RAGE signaling plays an important role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Receptor for amyloid beta peptide. Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons. ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Can also bind oligonucleotides. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs2070600 | |
| empty |
No binding partner found
Biological Process
Astrocyte activation
Cell surface receptor signaling pathway
Cellular response to amyloid-beta
Glucose mediated signaling pathway
Induction of positive chemotaxis
Inflammatory response
Innate immune response
Learning or memory
Microglial cell activation
Modulation of age-related behavioral decline
Negative regulation of blood circulation
Negative regulation of connective tissue replacement involved in inflammatory response wound healing
Negative regulation of interleukin-10 production
Negative regulation of long-term synaptic depression
Negative regulation of long-term synaptic potentiation
Neuron projection development
Positive regulation of activated T cell proliferation
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process
Positive regulation of chemokine biosynthetic process
Positive regulation of chemokine production
Positive regulation of dendritic cell differentiation
Positive regulation of endothelin production
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of heterotypic cell-cell adhesion
Positive regulation of interleukin-1 beta biosynthetic process
Positive regulation of interleukin-1 beta production
Positive regulation of interleukin-12 production
Positive regulation of interleukin-6 biosynthetic process
Positive regulation of interleukin-6 production
Positive regulation of JNK cascade
Positive regulation of JUN kinase activity
Positive regulation of monocyte chemotactic protein-1 production
Positive regulation of monocyte extravasation
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of p38MAPK cascade
Positive regulation of protein phosphorylation
Positive regulation of tumor necrosis factor biosynthetic process
Positive regulation of tumor necrosis factor production
Protein localization to membrane
Regulation of CD4-positive, alpha-beta T cell activation
Regulation of DNA binding
Regulation of inflammatory response
Regulation of long-term synaptic potentiation
Regulation of NIK/NF-kappaB signaling
Regulation of p38MAPK cascade
Regulation of spontaneous synaptic transmission
Regulation of synaptic plasticity
Regulation of T cell mediated cytotoxicity
Response to amyloid-beta
Response to hypoxia
Response to wounding
Transcytosis
Transport across blood-brain barrier
The reference OMIM entry for this protein is 600214
Advanced glycosylation end product-specific receptor; ager
Receptor for advanced glycation end products; rage
CLONING
Sugaya et al. (1994) identified 3 genes, AGER, PBX2 (176311), and NOTCH4 (164951), located 90 to 140 kb centromeric to the tenascin-like gene (600985) in the MHC class III region near the junction with class II. AGER is a member of the immunoglobulin superfamily.GENE FUNCTION
Yan et al. (1996) reported that the AGER protein, which they called RAGE, is an important receptor for the amyloid beta peptide (104760) and that expression of this receptor increases in Alzheimer disease (AD; 104300). They noted that expression of RAGE is particularly increased in neurons close to deposits of amyloid beta peptide and to neurofibrillary tangles. In mice, Deane et al. (2003) showed that RAGE mediated the transport of human beta-amyloid-40 and -42 across the blood-brain barrier and resulted in the expression of proinflammatory cytokines and endothelin-1 (EDN1; 131240), the latter causing cerebral vasoconstriction. Inhibition of the RAGE-ligand interaction, either by RAGE IgG or soluble RAGE, which is not transported across the blood-brain barrier, suppressed the accumulation of beta-amyloid in brain parenchyma in a mouse model of AD. Deane et al. (2003) suggested that RAGE could be a target for inhibiting the development of cerebral amyloidosis and its pathogenic consequences. Hofmann et al. (1999) reported that RAGE is a central cell surface receptor for S100A12 (603112), which they referred to as ENRAGE (extracellular newly identified RAGE-binding protein), and related members of the S100/calgranulin superfamily. Interaction of ENRAGE with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggered cellular activation, with generation of key proinflammatory mediators. In murine models, blockade of ENRAGE/RAGE quenched delayed-type hypersensitivity and inflammatory colitis by arresting activation of central signaling pathways and expression of inflammatory gene mediators. RAGE, a multiligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development, and inflammation, and certain diseases such as diabetes (see 125853, 222100) and Alzheimer disease. Engagement of RAGE by a ligand triggers activation of key cell signaling pathways, such as p21(ras) (see 139150), MAP kinases (see 176948), NF-kappa-B (NFKB; see 164011), and cdc42 (602590)/rac (602048), thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin (HMG1; 163905), a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the colocalization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumor invasion. Taguchi et al. (2000) demonstrated that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumors and tumors developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44 (601795)/p42 (603441), p38 (600289), and SAP/JNK (601158) MAP kinases, molecular effector mechanisms importantly linked to tumor proliferation, invasion, and expression of matrix metalloproteinases. Chavakis et al. (2003) found that Rage-deficient mice had impaired leukocyte recruitment in a thioglycollate-induced acute peritonitis model. Leukocyte recruitment to inflamed peritoneum was enhanced in diabetic wildtype mice comp ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: OMIM entry 600214 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).