EN-RAGE, also known as S100A12 and Calgranulin C, is a 10 kDa member of the S100 (soluble in 100% saturated ammonium sulfate) family of EF-hand calcium-binding proteins. Like other S100 proteins, S100A12 is small and generally acidic (1‑3). EN-RAGE forms noncovalent homodimers in the absence of divalent cations (4‑6); calcium and zinc promote the formation of higher order assemblies including tetramers and hexamers (4, 7, 8). The ability of S100A12 to chelate zinc enables it to inhibit the zinc-dependent metalloproteases MMP-2, -3, and -9 (8). S100A12 also forms heterodimers with S100A9 and binds to RAGE (Receptor for Advanced Glycation End-products), Annexin V, and several cytosolic enzymes involved in energy metabolism (9, 10). The hexameric form of EN-RAGE in particular binds RAGE with high affinity (7). EN-RAGE induces a variety of inflammatory responses including the in vivo recruitment of neutrophils, monocytes, and mast cells and the activation of mast cells and vascular endothelial cells (9, 11‑14). EN-RAGE is found at elevated levels under inflammatory conditions such as asthma, gout, rheumatoid arthritis synovial fluid, and atherosclerosis (8, 12, 14). S100A12 also promotes neurite outgrowth in isolated hippocampal neurons (15). An ortholog of S100A12 has not been identified in rodents, but the human protein is functional in mice and rats (11‑16).

References

Santamaria-Kisiel, L. et al. (2006) Biochem. J. 396:201.
Leclerc, E. et al. (2009) Biochim. Biophys. Acta 1793:993.
Wicki, R. et al. (1996) Cell Calcium 20:459.
Moroz, O.V. et al. (2009) BMC Biochem. 10:11.
Miranda, L.P. et al. (2001) FEBS Lett. 488:85.
Vogl, T. et al. (1999) J. Biol. Chem. 274:25291.
Xie, J. et al. (2007) J. Biol. Chem. 282:4218.
Goyette, J. et al. (2009) J. Immunol. 183:593.
Hatakeyama, T. et al. (2004) Eur. J. Biochem. 271:3765.
Hofmann, M.A. et al. (1999) Cell 97:889.
Yang, Z. et al. (2001) J. Leukoc. Biol. 69:986.
Rouleau, P. et al. (2003) Clin. Immunol. 107:46.
Yan, W.X. et al. (2008) J. Biol. Chem. 283:13035.
Yang, Z. et al. (2007) J. Allergy Clin. Immunol. 119:106.
Mikkelsen, S.E. et al. (2001) J. Neurochem. 79:767.
Fuellen, G. et al. (2004) OMICS 8:334.

Long Name

Extracellular Newly Identified RAGE-binding Protein

Alternate Names

CAAF1, CAAFI, CAGC, CAGCS100, Calgranulin C, ENRAGE, MRP6, S100A12

Entrez Gene IDs

6283 (Human)

Gene Symbol

S100A12

UniProt

P80511

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This product is provided under an intellectual property license from Life Technologies Corporation. The transfer of this product is conditioned on the buyer using the purchased product solely in research conducted by the buyer, excluding contract research or any fee for service research, and the buyer must not (1) use this product or its components for (a) diagnostic, therapeutic or prophylactic purposes; (b) testing, analysis or screening services, or information in return for compensation on a per-test basis; or (c) manufacturing or quality assurance or quality control, and/or (2) sell or transfer this product or its components for resale, whether or not resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5781 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@thermofisher.com.

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Human EN-RAGE/S100A12 Alexa Fluor™ Plus 594-conjugated Antibody

R&D Systems, part of Bio-Techne | Catalog # FAB10521AFP594

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Background: EN-RAGE/S100A12