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P50117

UniProt ID :

P50117

NCBI Taxonomy :

9986

Protein names :

Protein S100-A9

Organism :

Oryctolagus cuniculus

Taxonomy :

Eukaryota

Subcellular locations :

Secreted;Cytoplasm;Cytoplasm;Cell membrane;

Length :

132

Gene Ontology :

GO ID	Ontology	Definition	Evidence
GO:0005737	Cellular Component	cytoplasm	IEA
GO:0005856	Cellular Component	cytoskeleton	IEA
GO:0005576	Cellular Component	extracellular region	IEA
GO:0005634	Cellular Component	nucleus	IEA
GO:0005886	Cellular Component	plasma membrane	IEA
GO:0016209	Molecullar Function	antioxidant activity	IEA
GO:0005509	Molecullar Function	calcium ion binding	IEA
GO:0006919	Biological Process	activation of cysteine-type endopeptidase activity involved in apoptotic process	ISS
GO:0006914	Biological Process	autophagy	ISS
GO:0045087	Biological Process	innate immune response	IEA
GO:0002523	Biological Process	leukocyte migration involved in inflammatory response	ISS
GO:0070488	Biological Process	neutrophil aggregation	ISS
GO:0030593	Biological Process	neutrophil chemotaxis	ISS
GO:0050729	Biological Process	positive regulation of inflammatory response	ISS
GO:2001244	Biological Process	positive regulation of intrinsic apoptotic signaling pathway	ISS

Sequences :

MSCGMSQLERSIDTIINVFHQYSVRVGPRDSLSQKEFKQLVQKELHNFLKKEARDEKAINDIMEDLDTNQDKQLSFEEFVILMARLVHASHEEMHKNAPHDHEGHSHGPGLGGGGPGHGHGHSHGHGHGHSH

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 (By similarity).