S100A12

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities. The protein includes an antimicrobial peptide which has antibacterial activity. [provided by RefSeq, Nov 2014]

S100 Calcium Binding Protein A12

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 Zn2+ 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.

Biological Process antimicrobial humoral immune response mediated by antimicrobial peptideManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process defense response to bacteriumManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process defense response to fungusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process inflammatory responseManual Assertion Based On ExperimentTAS:ProtInc
Biological Process innate immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process killing of cells of another organismManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process mast cell activationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process monocyte chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process neutrophil chemotaxisManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of inflammatory responseManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of MAP kinase activityManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process xenobiotic metabolic processManual Assertion Based On ExperimentIDA:UniProtKB

Secreted
Cytoplasm
Cytoplasm, cytoskeleton
Cell membrane
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.