S100A8
Description
The S100A8 (S100 calcium binding protein A8) is a protein-coding gene located on chromosome 1.
S100 calcium-binding protein A8 (S100A8) is a protein that in humans is encoded by the S100A8 gene. It is also known as calgranulin A. The proteins S100A8 and S100A9 form a heterodimer called calprotectin. 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 may function in the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis and post COVID-19 condition.
S100A8 is a calcium- and zinc-binding protein that plays a significant role in regulating inflammatory processes and immune responses. It can induce neutrophil chemotaxis and adhesion. Primarily found as calprotectin (S100A8/A9), it exhibits a wide range of intra- and extracellular functions. Intracellular functions include facilitating leukocyte arachidonic acid trafficking and metabolism, modulating the tubulin-dependent cytoskeleton during phagocyte migration, and activating the neutrophilic NADPH-oxidase. It activates NADPH-oxidase by facilitating enzyme complex assembly at the cell membrane, transferring arachidonic acid (an essential cofactor) to the enzyme complex, and directly binding to NCF2/P67PHOX. Extracellular functions encompass pro-inflammatory, antimicrobial, oxidant-scavenging, and apoptosis-inducing activities. Its pro-inflammatory activity involves leukocyte recruitment, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. It acts as an alarmin or a danger associated molecular pattern (DAMP) molecule, stimulating innate immune cells via binding to pattern recognition receptors like Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates MAP-kinase and NF-kappa-B signaling pathways, amplifying the pro-inflammatory cascade. It exhibits antimicrobial activity against bacteria and fungi, likely achieved through chelation of Zn(2+), essential for microbial growth. It can induce cell death via autophagy and apoptosis, occurring through cross-talk between mitochondria and lysosomes via reactive oxygen species (ROS) involving BNIP3. It regulates neutrophil number and apoptosis by an anti-apoptotic effect, controlling cell survival through ITGAM/ITGB, TLR4, and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger protects against exaggerated tissue damage by scavenging oxidants. It can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN, and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity.
S100A8 is also known as 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag, MA387, MIF, MRP8, NIF, P8, S100-A8.
