S100A12: S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus. Belongs to the S-101 family.
Chromosomal Location of Human Ortholog: 1q21
Cellular Component: cytoskeleton; cytoplasm; extracellular region; plasma membrane; nucleus; cytosol
Molecular Function: protein binding; RAGE receptor binding; copper ion binding; zinc ion binding; calcium ion binding
Biological Process: neutrophil chemotaxis; positive regulation of MAP kinase activity; monocyte chemotaxis; positive regulation of I-kappaB kinase/NF-kappaB cascade; killing of cells of another organism; xenobiotic metabolic process; defense response to bacterium; innate immune response; inflammatory response; defense response to fungus; mast cell activation; cytokine secretion; activation of NF-kappaB transcription factor; positive regulation of inflammatory response
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