FEATURES

FAMILY

DESCRIPTION

Also known as S10A9_HUMAN, S100A9, CAGB, CFAG, MRP14. S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response (PubMed:12626582, PubMed:15331440, PubMed:20103766, PubMed:8423249, PubMed:16258195, PubMed:19122197, PubMed:21325622). It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism (PubMed:12626582, PubMed:15331440, PubMed:20103766). Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions (PubMed:8423249, PubMed:16258195, PubMed:19122197). The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase (PubMed:15331440, PubMed:21325622). Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX (PubMed:15642721, PubMed:22808130). The extracellular functions involve proinflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities (PubMed:8423249, PubMed:19534726). Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration (PubMed:15598812, PubMed:21487906). Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER) (PubMed:19402754). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade (PubMed:19402754, PubMed:22804476). Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth (PubMed:19087201). Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3 (PubMed:19935772). Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK (PubMed:22363402). Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants (PubMed:22489132, PubMed:21912088). Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread (PubMed:16258195). Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3 (PubMed:25417112). The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif (PubMed:25417112). Homodimer (PubMed:11851337, PubMed:16258195). Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9) (PubMed:16258195, PubMed:17553524, PubMed:19087201, PubMed:19122197, PubMed:8423249, PubMed:9083090, PubMed:25417112). S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions (PubMed:19402754). S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions (PubMed:19402754). S100A9 interacts with amyloid-beta protein 40 (PubMed:22457725). Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner (PubMed:11708798). Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes (PubMed:18786929). Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB (PubMed:15642721, PubMed:22808130). Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (PubMed:25417112).

EXTERNAL LINKS

S100A9

Mutations

Mutation(s) distribution

Mutations table