9u7m

Structural highlights

Function

S10AC_HUMAN 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.^{[1] [2] [3] [4]}

References

1. ↑ Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5-10. PMID:11522286
2. ↑ Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol. 2007 Jan;119(1):106-14. Epub 2006 Oct 6. PMID:17208591 doi:http://dx.doi.org/10.1016/j.jaci.2006.08.021
3. ↑ Yan WX, Armishaw C, Goyette J, Yang Z, Cai H, Alewood P, Geczy CL. Mast cell and monocyte recruitment by S100A12 and its hinge domain. J Biol Chem. 2008 May 9;283(19):13035-43. doi: 10.1074/jbc.M710388200. Epub 2008 , Feb 21. PMID:18292089 doi:http://dx.doi.org/10.1074/jbc.M710388200
4. ↑ Moroz OV, Burkitt W, Wittkowski H, He W, Ianoul A, Novitskaya V, Xie J, Polyakova O, Lednev IK, Shekhtman A, Derrick PJ, Bjoerk P, Foell D, Bronstein IB. Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function. BMC Biochem. 2009 Apr 23;10:11. doi: 10.1186/1471-2091-10-11. PMID:19386136 doi:http://dx.doi.org/10.1186/1471-2091-10-11