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Reviewed, UniProtKB/Swiss-Prot Q15109 (RAGE_HUMAN)

Last modified February 9, 2010. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Advanced glycosylation end product-specific receptor
Alternative name(s):
    Receptor for advanced glycosylation end products
Gene names
Name: AGER
Synonyms: RAGE
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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.

Subunit structure

Interacts with S100B, S100A1 and APP By similarity. Interacts with S100A12.

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein.

Isoform 2: Secreted.

Tissue specificity

Endothelial cells.

Sequence similarities

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q15109-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q15109-2)

Also known as: RAGESEC;

The sequence of this isoform differs from the canonical sequence as follows:
     54-67: Missing.
     275-404: GVPLPLPPSP...EAGESSTGGP → VSDLERGAGR...ACRTESVGGT

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 404382Advanced glycosylation end product-specific receptor
PRO_0000014923

Regions

Topological domain23 – 342320Extracellular Potential
Transmembrane343 – 36321 Potential
Topological domain364 – 40441Cytoplasmic Potential
Domain23 – 11694Ig-like V-type
Domain124 – 22198Ig-like C2-type 1
Domain227 – 31791Ig-like C2-type 2
Compositional bias380 – 3845Poly-Glu

Amino acid modifications

Glycosylation251N-linked (GlcNAc...) Potential
Glycosylation811N-linked (GlcNAc...) Potential
Disulfide bond38 ↔ 99 Potential
Disulfide bond144 ↔ 208 Potential
Disulfide bond259 ↔ 301 Potential

Natural variations

Alternative sequence54 – 6714Missing in isoform 2.
VSP_002551
Alternative sequence275 – 404130GVPLP…STGGP → VSDLERGAGRTRRGGANCRL CGRIRAGNSSPGPGDPGRPG DSRPAHWGHLVAKAATPRRG EEGPRKPGGRGGACRTESVG GT in isoform 2.
VSP_002552
Natural variant821G → S: dbSNP rs2070600. Ref.7
VAR_024500
Natural variant1001Q → R
VAR_011338

Experimental info

Sequence conflict11M → G in AAA03574. Ref.1

Secondary structure

................. 404
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 0D584C436C30CCE7

FASTA40442,803
        10         20         30         40         50         60 
MAAGTAVGAW VLVLSLWGAV VGAQNITARI GEPLVLKCKG APKKPPQRLE WKLNTGRTEA 

        70         80         90        100        110        120 
WKVLSPQGGG PWDSVARVLP NGSLFLPAVG IQDEGIFRCQ AMNRNGKETK SNYRVRVYQI 

       130        140        150        160        170        180 
PGKPEIVDSA SELTAGVPNK VGTCVSEGSY PAGTLSWHLD GKPLVPNEKG VSVKEQTRRH 

       190        200        210        220        230        240 
PETGLFTLQS ELMVTPARGG DPRPTFSCSF SPGLPRHRAL RTAPIQPRVW EPVPLEEVQL 

       250        260        270        280        290        300 
VVEPEGGAVA PGGTVTLTCE VPAQPSPQIH WMKDGVPLPL PPSPVLILPE IGPQDQGTYS 

       310        320        330        340        350        360 
CVATHSSHGP QESRAVSISI IEPGEEGPTA GSVGGSGLGT LALALGILGG LGTAALLIGV 

       370        380        390        400 
ILWQRRQRRG EERKAPENQE EEEERAELNQ SEEPEAGESS TGGP 

« Hide

Isoform 2 (RAGESEC).

Checksum: 35DDF66A13E39B38
Show »

FASTA34236,193

References

« Hide 'large scale' references
[1]"Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins."
Neeper M., Schmidt A.M., Brett J., Yan S.D., Wang F., Pan Y.C., Elliston K., Stern D., Shaw A.
J. Biol. Chem. 267:14998-15004(1992) [PubMed: 1378843] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Lung.
[2]"Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3."
Sugaya K., Fukagawa T., Matsumoto K., Mita K., Takahashi E., Ando A., Inoko H., Ikemura T.
Genomics 23:408-419(1994) [PubMed: 7835890] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]"Molecular heterogeneity of the receptor for advanced glycation endproducts."
Abedin M.J., Yonekura H., Migita H., Karasawa J., Yamamoto Y., Yamamoto H.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-100.
[4]"cDNA cloning of a novel secreted isoform of the human receptor for advanced glycation end products (RAGE) and characterization of cells co-expressing cell-surface scavenger receptors and Swedish mutant amyloid precursor protein."
Malherbe P., Richards J., Gaillard H., Thompson A., Diener C., Schuler A., Huber G.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse."
Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.
Genome Res. 13:2621-2636(2003) [PubMed: 14656967] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-82.
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[9]"Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy."
Hudson B.I., Stickland M.H., Futers T.S., Grant P.J.
Diabetes 50:1505-1511(2001) [PubMed: 11375354] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
[10]"Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function."
Moroz O.V., Burkitt W., Wittkowski H., He W., Ianoul A., Novitskaya V., Xie J., Polyakova O., Lednev I.K., Shekhtman A., Derrick P.J., Bjoerk P., Foell D., Bronstein I.B.
BMC Biochem. 10:11-11(2009) [PubMed: 19386136] [Abstract]
Cited for: INTERACTION WITH S100A12.
[11]"RAGE-dependent signaling in microglia contributes to neuroinflammation, A{beta} accumulation, and impaired learning/memory in a mouse model of Alzheimer's disease."
Fang F., Lue L.-F., Yan S., Xu H., Luddy J.S., Chen D., Walker D.G., Stern D.M., Yan S., Schmidt A.M., Chen J.X., Yan S.S.
FASEB J. 0:0-0(2009) [PubMed: 19906677] [Abstract]
Cited for: FUNCTION.
[12]"Solution structure of the third IG-like domain from human advanced glycosylation end product-specific receptor."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 235-323.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M91211 mRNA. Translation: AAA03574.1.
D28769 Genomic DNA. Translation: BAA05958.1.
AB036432 mRNA. Translation: BAA89369.1.
AJ133822 mRNA. Translation: CAB43108.1.
U89336 Genomic DNA. Translation: AAB47491.1.
AL662830 Genomic DNA. Translation: CAI17535.1.
AL662830 Genomic DNA. Translation: CAI17536.1.
AL662884 Genomic DNA. Translation: CAI18354.1.
AL662884 Genomic DNA. Translation: CAI18355.1.
AL845464 Genomic DNA. Translation: CAI41809.1.
AL845464 Genomic DNA. Translation: CAI41810.1.
BX284686 Genomic DNA. Translation: CAM26223.1.
BX927239 Genomic DNA. Translation: CAQ06596.1.
CR933878 Genomic DNA. Translation: CAQ09624.1.
CR812478 Genomic DNA. Translation: CAQ10699.1.
CH471081 Genomic DNA. Translation: EAX03610.1.
BC020669 mRNA. Translation: AAH20669.1.
AF208289 Genomic DNA. Translation: AAG35728.1.
IPIIPI00014810.
IPI00220335.
PIRI61596.
RefSeqNP_001127.1.
NP_751947.1.
UniGeneHs.534342

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PWImodel-A1-404[»]
2BJPmodel-A1-404[»]
2E5ENMR-A23-121[»]
2ENSNMR-A235-323[»]
3CJJX-ray1.85A23-240[»]
SMRQ15109. Positions 22-323.
ModBaseSearch...

Protein-protein interaction databases

IntActQ15109. 3 interactions.
STRINGQ15109.

Proteomic databases

PRIDEQ15109.

Genome annotation databases

EnsemblENST00000375070; ENSP00000364211; ENSG00000204305; Homo sapiens. [Genome view]
ENST00000375076; ENSP00000364217; ENSG00000204305; Homo sapiens. [Genome view]
ENST00000383280; ENSP00000372767; ENSG00000206320; Homo sapiens. [Genome view]
ENST00000411644; ENSP00000410213; ENSG00000234729; Homo sapiens. [Genome view]
ENST00000436456; ENSP00000397227; ENSG00000234729; Homo sapiens. [Genome view]
ENST00000436776; ENSP00000407164; ENSG00000237405; Homo sapiens. [Genome view]
ENST00000447921; ENSP00000395812; ENSG00000237405; Homo sapiens. [Genome view]
ENST00000451115; ENSP00000401068; ENSG00000206320; Homo sapiens. [Genome view]
ENST00000453042; ENSP00000396679; ENSG00000229058; Homo sapiens. [Genome view]
ENST00000456918; ENSP00000409457; ENSG00000229058; Homo sapiens. [Genome view]
GeneID177.
KEGGhsa:177.
UCSCuc003oal.1. human.
uc003oan.1. human.

Organism-specific databases

CTD177.
GeneCardsGC06M032256.
H-InvDBHIX0005749.
HIX0057955.
HIX0058132.
HGNCHGNC:320. AGER.
HPACAB011682.
MIM600214. gene.
PharmGKBPA24617.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ15109.
InParanoidQ15109.
PhylomeDBQ15109.

Enzyme and pathway databases

Pathway_Interaction_DBamb2_neutrophils_pathway. amb2 Integrin signaling.

Gene expression databases

CleanExHS_AGER.
HS_RAGE.
GenevestigatorQ15109.
GermOnlineENSG00000204305. Homo sapiens.

Family and domain databases

InterProIPR013162. CD80_C2-set.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003006. Ig/MHC_CS.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 2 hits.
PfamPF08205. C2-set_2. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 3 hits.
PS00290. IG_MHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio716.
SOURCESearch...

Entry information

Entry nameRAGE_HUMAN
AccessionPrimary (citable) accession number: Q15109
Secondary accession number(s): A2BFI7 expand/collapse secondary AC list , B0V176, Q15279, Q9H2X7, Q9Y3R3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: February 9, 2010
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents