RAGE_RAT
ID RAGE_RAT Reviewed; 402 AA.
AC Q63495;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Advanced glycosylation end product-specific receptor;
DE AltName: Full=Receptor for advanced glycosylation end products;
DE Flags: Precursor;
GN Name=Ager; Synonyms=Rage;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=9224812; DOI=10.1124/mol.52.1.54;
RA Renard C., Chappey O., Wautier M.P., Nagashima M., Lundh E., Morser J.,
RA Zhao L., Schmidt A.M., Scherrmann J.M., Wautier J.-L.;
RT "Recombinant advanced glycation end product receptor pharmacokinetics in
RT normal and diabetic rats.";
RL Mol. Pharmacol. 52:54-62(1997).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH S100B AND S100A1,
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=19910580; DOI=10.1161/circresaha.109.195834;
RA Tsoporis J.N., Izhar S., Leong-Poi H., Desjardins J.F., Huttunen H.J.,
RA Parker T.G.;
RT "S100B interaction with the receptor for advanced glycation end products
RT (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis
RT postinfarction.";
RL Circ. Res. 106:93-101(2010).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-389, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Mediates interactions of advanced glycosylation end products
CC (AGE). These are nonenzymatically glycosylated proteins which
CC accumulate in vascular tissue in aging and at an accelerated rate in
CC diabetes. Acts as a mediator of both acute and chronic vascular
CC inflammation in conditions such as atherosclerosis and in particular as
CC a complication of diabetes. AGE/RAGE signaling plays an important role
CC in regulating the production/expression of TNF-alpha, oxidative stress,
CC and endothelial dysfunction in type 2 diabetes. Interaction with
CC S100A12 on endothelium, mononuclear phagocytes, and lymphocytes
CC triggers cellular activation, with generation of key pro-inflammatory
CC mediators. Receptor for amyloid beta peptide. Contributes to the
CC translocation of amyloid-beta peptide (ABPP) across the cell membrane
CC from the extracellular to the intracellular space in cortical neurons.
CC ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-
CC activated protein kinase (MAPK), has the capacity to drive a transport
CC system delivering ABPP as a complex with RAGE to the intraneuronal
CC space. Can also bind oligonucleotides (By similarity). Interaction with
CC S100B after myocardial infarction may play a role in myocyte apoptosis
CC by activating ERK1/2 and p53/TP53 signaling. {ECO:0000250,
CC ECO:0000269|PubMed:19910580}.
CC -!- SUBUNIT: Interacts with S100A12, S100A14 and APP. Constitutive
CC homodimer; disulfide-linked (By similarity). Interacts with S100B and
CC S100A1. {ECO:0000250, ECO:0000269|PubMed:19910580}.
CC -!- INTERACTION:
CC Q63495; P04631: S100b; NbExp=3; IntAct=EBI-6479195, EBI-2696631;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:19910580}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:19910580}.
CC -!- TISSUE SPECIFICITY: Endothelial cells and cardiomyocytes.
CC {ECO:0000269|PubMed:19910580}.
CC -!- INDUCTION: Up-regulated in periinfarct ventricular myocardium.
CC {ECO:0000269|PubMed:19910580}.
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DR EMBL; L33413; AAA42027.1; -; mRNA.
DR AlphaFoldDB; Q63495; -.
DR SMR; Q63495; -.
DR IntAct; Q63495; 2.
DR STRING; 10116.ENSRNOP00000000508; -.
DR BindingDB; Q63495; -.
DR ChEMBL; CHEMBL2176847; -.
DR GlyGen; Q63495; 2 sites.
DR iPTMnet; Q63495; -.
DR PhosphoSitePlus; Q63495; -.
DR PaxDb; Q63495; -.
DR UCSC; RGD:69258; rat.
DR RGD; 69258; Ager.
DR eggNOG; ENOG502SQ8N; Eukaryota.
DR InParanoid; Q63495; -.
DR PhylomeDB; Q63495; -.
DR Reactome; R-RNO-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-RNO-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-RNO-933542; TRAF6 mediated NF-kB activation.
DR PRO; PR:Q63495; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0070379; F:high mobility group box 1 binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0044548; F:S100 protein binding; IPI:RGD.
DR GO; GO:0038023; F:signaling receptor activity; ISO:RGD.
DR GO; GO:0048143; P:astrocyte activation; ISO:RGD.
DR GO; GO:0014002; P:astrocyte development; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010255; P:glucose mediated signaling pathway; ISO:RGD.
DR GO; GO:0009100; P:glycoprotein metabolic process; IEP:RGD.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0001774; P:microglial cell activation; ISO:RGD.
DR GO; GO:1903523; P:negative regulation of blood circulation; ISO:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:RGD.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IMP:RGD.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:RGD.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:1900453; P:negative regulation of long-term synaptic depression; ISO:RGD.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEP:RGD.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0031175; P:neuron projection development; IMP:RGD.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; ISO:RGD.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:RGD.
DR GO; GO:1904472; P:positive regulation of endothelin production; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IMP:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD.
DR GO; GO:2000439; P:positive regulation of monocyte extravasation; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:RGD.
DR GO; GO:0060100; P:positive regulation of phagocytosis, engulfment; IMP:RGD.
DR GO; GO:1901018; P:positive regulation of potassium ion transmembrane transporter activity; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:2000676; P:positive regulation of type B pancreatic cell apoptotic process; IMP:RGD.
DR GO; GO:0072657; P:protein localization to membrane; ISO:RGD.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IMP:RGD.
DR GO; GO:2000514; P:regulation of CD4-positive, alpha-beta T cell activation; ISO:RGD.
DR GO; GO:0051101; P:regulation of DNA binding; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:1900744; P:regulation of p38MAPK cascade; ISO:RGD.
DR GO; GO:0150003; P:regulation of spontaneous synaptic transmission; ISO:RGD.
DR GO; GO:0001914; P:regulation of T cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:1904645; P:response to amyloid-beta; ISO:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0033595; P:response to genistein; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0051595; P:response to methylglyoxal; IEP:RGD.
DR GO; GO:0072714; P:response to selenite ion; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0045056; P:transcytosis; ISO:RGD.
DR GO; GO:0060290; P:transdifferentiation; IEP:RGD.
DR GO; GO:0150104; P:transport across blood-brain barrier; ISO:RGD.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF13895; Ig_2; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Inflammatory response;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..402
FT /note="Advanced glycosylation end product-specific
FT receptor"
FT /id="PRO_0000014925"
FT TOPO_DOM 23..341
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 23..109
FT /note="Ig-like V-type"
FT DOMAIN 123..219
FT /note="Ig-like C2-type 1"
FT DOMAIN 233..315
FT /note="Ig-like C2-type 2"
FT REGION 368..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 38..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 143..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 257
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 299
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 402 AA; 42664 MW; 594481BC3A51E94E CRC64;
MPTGTVARAW VLVLALWGAV AGGQNITARI GEPLMLSCKG APKKPTQKLE WKLNTGRTEA
WKVLSPQGDP WDSVARILPN GSLLLPAIGI VDEGTFRCRA TNRLGKEVKS NYRVRVYQIP
GKPEIVNPAS ELTANVPNKV GTCVSEGSYP AGTLSWHLDG KPLIPDGKGT VVKEETRRHP
ETGLFTLRSE LTVTPAQGGT TPTYSCSFSL GLPRRRPLNT APIQPRVREP LPPEGIQLLV
EPEGGTVAPG GTVTLTCAIS AQPPPQIHWI KDGTPLPLAP SPVLLLPEVG HEDEGIYSCV
ATHPSHGPQE SPPVNIRVTE TGDEGQAAGS VDGSGLGTLA LALGILGGLG IAALLIGAIL
WRKRQPRLEE RKAPESQEDE EERAELNQSE EAEMPENGAG GP
