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Table 1.

Receptors for advanced glycation end products—structure and function.

AGE-binding protein Molecular weight Cell types Structural features Ligands Function
RAGE Sequence: Monocytes/Macrophages, T-lymphocytes (CD4+, CD8+), endothelial cells, mesangial cells, fibroblasts, smooth muscle cells, neuronal cells Highly acidic cytoplasmic domain, a single transmembrane domain, extracellular domain consisting of VC1-ligand binding domain and C2 domain S100 proteins, HMGB-1, β-amyloid, amyloid fibrils, β-integrin Mac-1, AGEs Endocytosis, signaling (cell activation)→generation of ROS, inflammatory response
fl-RAGE: ~43 kDa
sRAGE: ~36 kDa
N-truncated RAGE: ~32 kDa
Western Blot (WB):
fl-RAGE: ~55 kDa
sRAGE: ~46–50 kDa
N-truncated RAGE: ~42 kDa



AGE-R1/OST-48/p60 ~50 kDa (Sequence +WB) Monocytes/macrophages, T-lymphocytes (CD4+, CD8+), Endothelial cells, mesangial cells, fibroblasts, smooth muscle cells, neuronal cells Integral plasma membrane protein with a single transmembrane domain, formation of a complex with ribophorin I, II and DAD1 in the RER - Endocytic uptake and degradation of AGE-modified proteins, protective against oxidative stress



AGE-R2/80K-H/p90 Sequence: ~59 kDa Monocytes/macrophages, T-lymphocytes (CD4+, CD8+), endothelial cells, mesangial cells, fibroblasts, smooth muscle cells, neuronal cells No transmembrane domain, phosphorylation on tyrosine residues, formation of a complex with PKCζ and munc18c AGEs Signaling (cell activation), regulatory subunit of glucosidase II
WB: ~80 kDa



AGE-R3/galectin-3 Sequence: ~26 kDa Monocytes/macrophages, T-lymphocytes (CD4+, CD8+), endothelial cells, mesangial cells, fibroblasts, smooth muscle cells, neuronal cells Formerly known as Mac-2 or CBP-35, consists of a carbohydrate-binding C-terminal domain, PGAY-rich repeating domain, N-terminal domain, no transmembrane domain Cell surface: IgE receptor, colon cancer mucin, CD66, LPS, Mac-1, Mac-3, heavy chain of CD98, myelin-associated glycoprotein, lysosomal-membrane-associated glycoproteins (LAMPs) 1 and 2; extracellular environment: AGEs, IgE, laminin, tenascin, fibronectin, collagen IV, gp90/Mac-2 binding protein Signaling (cell activation)
WB: ~32 kDa



SR-A (I/II) Sequence: ~50 kDa (monomeric subunit) Monocytes/macrophages, dendritic cells, endothelial cells Domain I: cytoplasmic N-terminus, Domain II: transmembrane domain, Domain III: spacer domain, Domain IV: α-helical coiled-coil, Domain V: collagen triple helix, Domain VI: C-terminal domain Endogenous ligands: AcLDL, OxLDL, AGE, β-amyloid; Pathogen recognition: Gram-negative bacteria (E. coli), Gram-positive bacteria (S. aureus), bacterial DNA, LTA Endocytic uptake and degradation of modified LDL and AGE-modified proteins
WB: ~77 kDa (monomer), ~220 kDa (homotrimer)



SR-B/CD36 Sequence: ~53 kDa Platelets, endothelial cells, epithelial cells, adipocytes, B-lymphocytes Two transmembrane domains with an extracellular loop, palmitoylated on cysteine residues, two on each N- and C-terminus Endogenous ligands: AcLDL, OxLDL, HDL, LDL, VLDL, collagen, thrombospondin, long chain fatty acids, maleylated BSA, anionic phospholipids, AGE, apoptotic cells; Pathogen recognition: Microbial diacylglycerides, S. aureus Endocytic uptake and degradation of AGEs, cell adhesion, regulator of fatty acid transport
WB: ~88 kDa



SR-BI Sequence: ~60 kDa Tissues which are active in selective uptake of HDL (liver, steroidogenic) Two transmembrane domains with an extracellular loop, palmitoylated on C-terminal Cys462 and Cys470 AcLDL, OxLDL, LDL, HDL, VLDL, maleylated BSA, anionic phospholipids, AGE Selective uptake of HDL, endocytic uptake and degradation of AGEs
WB: ~76 kDa



SR-E/LOX-1 Sequence: ~31 kDa Endothelial cells, macrophages, smooth muscle cells Group V C-type lectin, short N-terminal cytoplasmic domain, single transmembrane domain, extracellular NECK domain with a subsequent CTLD Endogenous ligands: OxLDL, Hsp70, AGE, apoptotic cells, activated platelets; Pathogen recognition: S. aureus, E. coli Endocytic uptake and degradation of modified oxLDL, signaling
WB: ~50 kDa



FEEL-1/FEEL-2 FEEL-1: ~275 kDa Endothelial cells, monocytes/macrophages Type I transmembrane protein, consists of 7 fasciclins, 16 EGF-like, 2 laminin-type EGF-like and 1 link domain transmembrane region Endogenous ligands: AcLDL, AGE, SPARC, hyaluronic acid; pathogen recognition: S. aureus, E. coli Endocytic uptake and degradation of AGEs, Hyaluronic acid and AcLDL
FEEL-2: ~277 kDa (sequence)
190 kDa form stabilin-2 (by proteolytic cleavage): ~190 kDa (WB), ~154 kDa (sequence)