S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its pro-inflammatory 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 pro-inflammatory 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 (By similarity). Homodimer. Homooligomer (tetramer or hexamer) in the presence of calcium, zinc and copper ions. Interacts with AGER and both calcium and zinc are essential for the interaction (By similarity). Interacts with CACYBP in a calcium-dependent manner (By similarity). Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation is secreted via a microtubule-mediated, alternative pathway (By similarity). Found essentially in granulocytes with small amounts found in lymphocytes. The hinge domain contributes significantly to its chemotactic properties. In the absence of zinc binds one calcium ion per molecule, in the presence of zinc binds two calcium ions per molecule. Belongs to the S-100 family.