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MGP002743

UniProt Annotations

Entry Information

Gene Name	S100 calcium binding protein A12
Protein Entry	S10AC_HUMAN
UniProt ID	P80511
Species	Human

Comments

Comment type	Description
Domain	The hinge domain contributes significantly to its chemotactic properties. {ECO:0000269\|PubMed:18292089}.
Function	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. {ECO:0000269\|PubMed:11522286, ECO:0000269\|PubMed:17208591, ECO:0000269\|PubMed:18292089, ECO:0000269\|PubMed:19386136}.
Mass Spectrometry	Mass=10444; Method=Electrospray; Range=2-92; Evidence={ECO:0000269\|PubMed:11522286};
Mass Spectrometry	Mass=1688.9; Method=MALDI; Range=78-92; Evidence={ECO:0000269\|PubMed:11522286};
Similarity	Belongs to the S-100 family. {ECO:0000305}.
Similarity	Contains 2 EF-hand domains. {ECO:0000255\|PROSITE- ProRule:PRU00448}.
Subcellular Location	Secreted {ECO:0000269\|PubMed:22811950}. Cytoplasm {ECO:0000269\|PubMed:22811950}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:22811950}. Cell membrane {ECO:0000269\|PubMed:22811950}; Peripheral membrane protein {ECO:0000269\|PubMed:22811950}. Note=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.
Subunit	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. Interacts with CACYBP in a calcium-dependent manner. {ECO:0000269\|PubMed:12042313, ECO:0000269\|PubMed:19386136}.
Tissue Specificity	Predominantly expressed by neutrophils, monocytes and activated macrophages. Expressed by eosinophils and macrophages in asthmatic airways in regions where mast cells accumulate. Found in high concentrations in the serum of patients suffering from various inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and Kawasaki disease.