P50116
UniProt ID : P50116
NCBI Taxonomy : 10116
Protein names : Protein S100-A9
Organism : Rattus norvegicus
Taxonomy : Eukaryota
Subcellular locations :Secreted;Cytoplasm;Cytoplasm;Cell membrane;
Length : 113
Gene Ontology :
GO IDOntologyDefinitionEvidence
GO:0005737Cellular ComponentcytoplasmIEA
GO:0005856Cellular ComponentcytoskeletonIEA
GO:0005615Cellular Componentextracellular spaceIDA
GO:0005634Cellular ComponentnucleusIEA
GO:0005886Cellular Componentplasma membraneIEA
GO:0016209Molecullar Functionantioxidant activityIEA
GO:0005509Molecullar Functioncalcium ion bindingIEA
GO:0031532Biological Processactin cytoskeleton reorganizationIEA
GO:0006919Biological Processactivation of cysteine-type endopeptidase activity involved in apoptotic processISS
GO:0006914Biological ProcessautophagyISS
GO:0002544Biological Processchronic inflammatory responseIEP
GO:0045087Biological Processinnate immune responseIEA
GO:0002523Biological Processleukocyte migration involved in inflammatory responseISS
GO:0070488Biological Processneutrophil aggregationISS
GO:0030593Biological Processneutrophil chemotaxisISS
GO:0050729Biological Processpositive regulation of inflammatory responseISS
GO:2001244Biological Processpositive regulation of intrinsic apoptotic signaling pathwayISS
GO:0045113Biological Processregulation of integrin biosynthetic processIEA
GO:0045471Biological Processresponse to ethanolIEP
GO:0032496Biological Processresponse to lipopolysaccharideIEP
GO:0010043Biological Processresponse to zinc ionIEP
SWISS-MODEL Repository :P50116
Sequences : MAAKTGSQLERSISTIINVFHQYSRKYGHPDTLNKAEFKEMVNKDLPNFLKREKRNENLLRDIMEDLDTNQDNQLSFEECMMLMGKLIFACHEKLHENNPRGHDHSHGKGCGK
Function :S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. 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. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. 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. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes 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 pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. 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. 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. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants.