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FLASH GENE
Symbol AGER contributors: mct - updated : 18-06-2015
HGNC name advanced glycosylation end product-specific receptor
HGNC id 320
Location 6p21.32      Physical location : 3.409.765 - 32.152.023
Synonym name
  • receptor for advanced glycosylation end-products
  • advanced glycosylation end product-specific receptor
  • variant sRAGE1
  • RAGE isoform NtRAGE-delta
  • RAGE isoform sRAGE-delta
  • Synonym symbol(s) RAGE, DAQB-143M3.1, MGC22357
    DNA
    TYPE functioning gene
    STRUCTURE 3.28 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    BAT8 6p21.31 HLA-B associated transcript 8 C6orf46 6p21.31 chromosome 6 open reading frame 46 C2 6p21.3 complement component 2 BF 6p21.3 B-factor, properdin RDBP 6p21.33 RD RNA binding protein SKIV2L 6p21.3 superkiller viralicidic activity 2-like (S. cerevisiae) DOM3Z 6p21.3 dom-3 homolog Z (C. elegans) STK19 6p21.3 serine/threonine kinase 19 C4B 6p21.3 complement component 4B CYP21A2 6p21.3 cytochrome P450, family 21, subfamily A, polypeptide 2 TNXB 6p21.3 tenascin XB CREBL1 6p21.3 cAMP responsive element binding protein-like 1 FKBPL 6p21.3 FK506 binding protein like C6orf31 6p21.1 chromosome 6 open reading frame 31 PPT2 6p21.3 palmitoyl-protein thioesterase 2 EGFL8 6p21.31 EGF-like-domain, multiple 8 AGPAT1 6p21.3 1-acylglycerol-3-phosphate O-acyltransferase 1 (lysophosphatidic acid acyltransferase, alpha) RNF5 6p21.31 ring finger protein 5 AGER 6p21.3 advanced glycosylation end product-specific receptor PBX2 6p21.3 pre-B-cell leukemia transcription factor 2 C6orf9 6p21.3 chromosome 6 open reading frame 9 NOTCH4 6p21.3 Notch homolog 4 (Drosophila) C6orf10 6p21.3 chromosome 6 open reading frame 10 BTNL2 6p21.3 butyrophilin-like 2 (MHC class II associated)
    regionally located contiguous to PBX2 in the MHC class III region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1414 - 404 - 2009 19061941
    plasma membrane
    10 - 1259 - 342 - 2009 19061941
    extracellular
    8 - 665 - 133 - 2009 19061941
    Deletion: 80 bp exon2, exon3, exon 4, exon 5, 120 bp exon6
    11 - 1398 - 303 - 2009 19061941
    Insertion: intron 1
    10 - 1371 - 294 - 2009 19061941
    insertion: intron 1/deletion: exon 9
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
     vessel     Homo sapiens
    Hearing/EquilibriumearinnercochleaCortihighly Homo sapiens
    Respiratorylung     Homo sapiens
    Visualeye    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Hearing / Equilibriumcochlea cell Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiensAdult
    not specificfibroblast Homo sapiensAdult
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye
    PROTEIN
    PHYSICAL PROPERTIES fibrous ,globular
    STRUCTURE
    motifs/domains
  • one immunoglobulin-like V-type domain
  • two immunoglobulin-like C2-type domains
  • a extracellular domain (322AAs), ex-RAGE functioning as a "decoy" to RAGE-ligand interaction and thus potentially dampening inflammatory conditions
  • a transmembrane domain (19AAs)
  • a cytosol domain (41AAs)
  • the behavior of the cytoplasmic tail is strongly affected by its being part of the whole receptor
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • immunoglobulin superfamily of cell surface molecules
  • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • one membrane anchored, one secreted form
  • cell surface-located type I membrane protein
  • AGER dimerization occurs in the endoplasmic reticulum (ER) (
  • basic FUNCTION
  • mediating amyloid beta peptide effect on neurons and microglia and mediating the amyloid -beta peptide transport across the blood -brain barrier and accumulation in brain
  • playing distinct functional roles in both the toxicity and disposal of advanced glycation end products (AGEs), substances that are linked to diabetes and aging
  • may play an important role in inflammatory processes and endothelial activation, likely to accelerate the processes of coronary atherosclerotic development, especially in diabetic patients
  • play an important role in the internalization of Mycobacterium tuberculosis into macrophages
  • mediates responses to cell danger and stress
  • RAGE activates programs responsible for acute and chronic inflammation, when bound by its many ligands
  • implicated as a pro-inflammatory factor in chronic inflammatory conditions such as diabetes mellitus and rheumatoid arthritis
  • plays an important role in the development and progression of vascular disease
  • together with caspase-3 activation and inhibition of NF-kappaB signaling pathways, might be involved in the pathogenesis of macrophage apoptosis induced by HMGB1
  • contributes to the inflammatory response in many acute and chronic diseases
  • AGER and ICAM1 are a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute trauma-induced inflammatory response
  • induces the expression of thioredoxin interacting protein (TXNIP) in Schwann cells and the injured sciatic nerve)
  • AGER and ICAM1 differentially regulate leukocyte adhesion in a stimulus-dependent manner
  • prominent role in the survival and development of prostate tumor growth
  • is required for the activation of interleukin 6 (IL6)–mediated mitochondrial signal transducers and activators of transcription 3 (STAT3) signaling in pancreatic carcinogenesis
  • is required for the mitochondrial localization of STAT3 in pancreatic cancer cells
  • AGER-mediated autophagy is required for enhanced ATP production and proliferation in pancreatic cancer cells, mostly via regulation of mitochondrial STAT3
  • expression of AGER on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses
  • RETN, S100A12 and AGER are involved in the pathophysiology of Kawasaki disease (KD)
  • novel roles for AGER as a conduit for LPA (phospholipid lysophosphatidic acid) signaling
  • key molecule in the onset and sustainment of the inflammatory response
  • expression in keratinocytes is critically involved in the perpetuation of acute inflammation, supporting the central role of AGER in paracrine communication between keratinocytes and stromal immune cells
  • major receptor that mediates vascular inflammation
  • AGER-heparan sulfate oligomeric complexes are essential for signaling and interfering with AGER oligomerization might be of therapeutic value
  • is an inflammation perpetuating multi-ligand receptor and participates actively in various vascular and inflammatory diseases even in normoglycaemic conditions
  • is a multifunctional receptor implicated in diverse processes including inflammation and cancer
  • functional role for AGER/S100A7 signaling in linking inflammation to aggressive breast cancer development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • PLCB1/CAMK4-NFKB1 is involved in AGER mediated signaling pathway in human endothelial cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • many ligands, endo or exogenous
  • interacting with EGFR
  • interact with various ligands amphoterin also known as HMGB1, amyloid beta, proteins of the S100/calgranulin family and ITGAM(
  • S100A12 is a small calcium binding protein that is a ligand of AGER
  • agonist S100A4, fusion protein of RAGE encompassing the extracellular domain of RAGE (ex-RAGE), ex-RAGE followed by S100A4, or S100A4 followed by ex-RAGE
  • interaction of HMGB1 and AGER is a key component initiating and sustaining the inflammatory response in inflammatory cardiomyopathy eventually leading to heart failure
  • S100B receptor is AGER
  • binding of S100B to AGER results in stimulation of AGER anti-mitogenic and promyogenic signaling
  • functional interaction between AGER and TLRs coordinately regulates inflammation, immune response and other cellular functions
  • AGER is a native C1QA, C1QB, C1QC globular domain receptor (C1q and AGER are linked to the recruitment of leukocytes and phagocytosis of C1q-coated material)
  • HMGB1 is one of the important AGER ligands
  • mediate its activity through modulation of the IL6/STAT3 pathway
  • can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble AGER form
  • DOCK7 bound to the AGER cytoplasmic domain and transduced a signal to CDC42, resulting in the formation of abundant highly branched filopodia-like protrusions, dendritic pseudopodia
  • HMGB1 promotes an inflammatory response by inducing the expression of ICAM1 and P-selectin via AGER-mediated stimulation of the endoplasmic reticulum stress pathway
  • in ERMS cells, AGER upregulates myogenin which upregulates MYOD1 and downregulates PAX7, with consequent inhibition of proliferation and stimulation of differentiation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in cerebral vasculature of Alzheimer's disease patients
    constitutional     --over  
    increased in preeclampsia (Fasshauer 2008)
    constitutional     --over  
    in patients with pulmonary tuberculosis as well as in diabetics
    constitutional       gain of function
    implicated in numerous pathological states including vascular disease, diabetes, cancer, and neurodegeneration
    Susceptibility to type 1 diabetes
    Variant & Polymorphism SNP , other -374 T/A polymorphism associated to type 1 diabetes
    Candidate gene
    Marker
  • CCNB2, AGER, CDK5RAP3, may be used as a very reliable biomarker of lung adenocarcinoma
  • mRNA expression of S100A12 and AGER might be as a useful biomarker for Transitional cell carcinoma (TCC)
  • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    therapeutic intervention targeted at the AGER gene may be a useful means of treating pathologies of the vasculature
    neurologyneurodegenerativealzheimer
    pharmacological stimulation of AGER shedding might open alternative treatment strategies for Alzheimer disease
    diabete  
    pharmacological stimulation of AGER shedding might open alternative treatment strategies for diabetes-induced inflammation
    cardiovascularaquired 
    therapeutic antagonism of RAGE might be a unique target for therapeutic intervention in heart failure
    ANIMAL & CELL MODELS
  • Rage-deficient mice displayed a reduced propensity for breast tumor growth