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Protein

Advanced glycosylation end product-specific receptor

Gene

Ager

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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 (By similarity). Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling.By similarity1 Publication

GO - Molecular functioni

  • advanced glycation end-product receptor activity Source: RGD
  • high mobility group box 1 binding Source: RGD
  • S100 protein binding Source: RGD

GO - Biological processi

  • brain development Source: RGD
  • calcium ion homeostasis Source: RGD
  • cellular response to drug Source: RGD
  • cellular response to fatty acid Source: RGD
  • cellular response to glucose stimulus Source: RGD
  • cellular response to hydrogen peroxide Source: RGD
  • cellular response to organic cyclic compound Source: RGD
  • glycoprotein metabolic process Source: RGD
  • inflammatory response Source: UniProtKB-KW
  • JAK-STAT cascade Source: RGD
  • lung development Source: RGD
  • negative regulation of cell adhesion Source: RGD
  • negative regulation of collagen biosynthetic process Source: RGD
  • negative regulation of endothelial cell migration Source: RGD
  • negative regulation of endothelial cell proliferation Source: RGD
  • negative regulation of osteoblast proliferation Source: RGD
  • negative regulation of protein phosphorylation Source: RGD
  • neuron projection development Source: UniProtKB
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of autophagy Source: RGD
  • positive regulation of cell migration Source: RGD
  • positive regulation of endothelial cell apoptotic process Source: RGD
  • positive regulation of epithelial to mesenchymal transition Source: RGD
  • positive regulation of fibroblast migration Source: RGD
  • positive regulation of fibroblast proliferation Source: RGD
  • positive regulation of gene expression Source: RGD
  • positive regulation of inflammatory response Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • positive regulation of neuron death Source: RGD
  • positive regulation of phagocytosis, engulfment Source: RGD
  • positive regulation of potassium ion transmembrane transporter activity Source: RGD
  • positive regulation of protein phosphorylation Source: RGD
  • positive regulation of reactive oxygen species metabolic process Source: RGD
  • positive regulation of smooth muscle cell migration Source: RGD
  • positive regulation of smooth muscle cell proliferation Source: RGD
  • positive regulation of type B pancreatic cell apoptotic process Source: RGD
  • response to activity Source: RGD
  • response to fructose Source: RGD
  • response to genistein Source: RGD
  • response to hyperoxia Source: RGD
  • response to methylglyoxal Source: RGD
  • response to selenite ion Source: RGD
  • response to vitamin A Source: RGD
  • transdifferentiation Source: RGD
Complete GO annotation...

Keywords - Biological processi

Inflammatory response

Names & Taxonomyi

Protein namesi
Recommended name:
Advanced glycosylation end product-specific receptor
Alternative name(s):
Receptor for advanced glycosylation end products
Gene namesi
Name:Ager
Synonyms:Rage
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69258. Ager.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 341319ExtracellularSequence analysisAdd
BLAST
Transmembranei342 – 36221HelicalSequence analysisAdd
BLAST
Topological domaini363 – 40240CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • axon Source: RGD
  • basal plasma membrane Source: RGD
  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • extracellular space Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • neuronal cell body Source: RGD
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2176847.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 402380Advanced glycosylation end product-specific receptorPRO_0000014925Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi25 – 251N-linked (GlcNAc...)Sequence analysis
Disulfide bondi38 ↔ 98PROSITE-ProRule annotation
Glycosylationi80 – 801N-linked (GlcNAc...)Sequence analysis
Disulfide bondi143 ↔ 206PROSITE-ProRule annotation
Disulfide bondi257 – 257InterchainPROSITE-ProRule annotation
Disulfide bondi299 – 299InterchainPROSITE-ProRule annotation
Modified residuei376 – 3761PhosphoserineCombined sources
Modified residuei389 – 3891PhosphoserineCombined sources

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ63495.
PRIDEiQ63495.

PTM databases

iPTMnetiQ63495.
PhosphoSiteiQ63495.

Expressioni

Tissue specificityi

Endothelial cells and cardiomyocytes.1 Publication

Inductioni

Up-regulated in periinfarct ventricular myocardium.1 Publication

Interactioni

Subunit structurei

Interacts with S100A12, S100A14 and APP. Constitutive homodimer; disulfide-linked (By similarity). Interacts with S100B and S100A1.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
S100bP046313EBI-6479195,EBI-2696631

GO - Molecular functioni

  • high mobility group box 1 binding Source: RGD
  • S100 protein binding Source: RGD

Protein-protein interaction databases

IntActiQ63495. 2 interactions.
STRINGi10116.ENSRNOP00000000508.

Structurei

3D structure databases

ProteinModelPortaliQ63495.
SMRiQ63495. Positions 21-120, 234-320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 10987Ig-like V-typeAdd
BLAST
Domaini123 – 21997Ig-like C2-type 1Add
BLAST
Domaini233 – 31583Ig-like C2-type 2Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IVT2. Eukaryota.
ENOG4111C4I. LUCA.
HOGENOMiHOG000232122.
HOVERGENiHBG004350.
InParanoidiQ63495.
PhylomeDBiQ63495.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
PF13895. Ig_2. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00408. IGc2. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63495-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPTGTVARAW VLVLALWGAV AGGQNITARI GEPLMLSCKG APKKPTQKLE
60 70 80 90 100
WKLNTGRTEA WKVLSPQGDP WDSVARILPN GSLLLPAIGI VDEGTFRCRA
110 120 130 140 150
TNRLGKEVKS NYRVRVYQIP GKPEIVNPAS ELTANVPNKV GTCVSEGSYP
160 170 180 190 200
AGTLSWHLDG KPLIPDGKGT VVKEETRRHP ETGLFTLRSE LTVTPAQGGT
210 220 230 240 250
TPTYSCSFSL GLPRRRPLNT APIQPRVREP LPPEGIQLLV EPEGGTVAPG
260 270 280 290 300
GTVTLTCAIS AQPPPQIHWI KDGTPLPLAP SPVLLLPEVG HEDEGIYSCV
310 320 330 340 350
ATHPSHGPQE SPPVNIRVTE TGDEGQAAGS VDGSGLGTLA LALGILGGLG
360 370 380 390 400
IAALLIGAIL WRKRQPRLEE RKAPESQEDE EERAELNQSE EAEMPENGAG

GP
Length:402
Mass (Da):42,664
Last modified:November 1, 1997 - v1
Checksum:i594481BC3A51E94E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33413 mRNA. Translation: AAA42027.1.
UniGeneiRn.9829.

Genome annotation databases

UCSCiRGD:69258. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33413 mRNA. Translation: AAA42027.1.
UniGeneiRn.9829.

3D structure databases

ProteinModelPortaliQ63495.
SMRiQ63495. Positions 21-120, 234-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63495. 2 interactions.
STRINGi10116.ENSRNOP00000000508.

Chemistry

ChEMBLiCHEMBL2176847.

PTM databases

iPTMnetiQ63495.
PhosphoSiteiQ63495.

Proteomic databases

PaxDbiQ63495.
PRIDEiQ63495.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:69258. rat.

Organism-specific databases

RGDi69258. Ager.

Phylogenomic databases

eggNOGiENOG410IVT2. Eukaryota.
ENOG4111C4I. LUCA.
HOGENOMiHOG000232122.
HOVERGENiHBG004350.
InParanoidiQ63495.
PhylomeDBiQ63495.

Miscellaneous databases

PROiQ63495.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR013162. CD80_C2-set.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]
PfamiPF08205. C2-set_2. 1 hit.
PF13895. Ig_2. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
SM00408. IGc2. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats."
    Renard C., Chappey O., Wautier M.P., Nagashima M., Lundh E., Morser J., Zhao L., Schmidt A.M., Scherrmann J.M., Wautier J.-L.
    Mol. Pharmacol. 52:54-62(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Lung.
  2. "S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction."
    Tsoporis J.N., Izhar S., Leong-Poi H., Desjardins J.F., Huttunen H.J., Parker T.G.
    Circ. Res. 106:93-101(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH S100B AND S100A1, INDUCTION, TISSUE SPECIFICITY.
  3. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-389, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiRAGE_RAT
AccessioniPrimary (citable) accession number: Q63495
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 11, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.