P50115 |
UniProt ID : |
P50115 |
NCBI Taxonomy : |
10116 |
Protein names : |
Protein S100-A8 |
Organism : |
Rattus norvegicus |
Taxonomy : |
Eukaryota |
Subcellular locations : | Secreted;Cytoplasm;Cytoplasm;Cell membrane; |
Length : |
89 |
Gene Ontology : | GO ID | Ontology | Definition | Evidence | GO:0005737 | Cellular Component | cytoplasm | IEA | GO:0005856 | Cellular Component | cytoskeleton | IEA | GO:0005615 | Cellular Component | extracellular space | IDA | 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:0002526 | Biological Process | acute inflammatory response | IEP | GO:0006914 | Biological Process | autophagy | ISS | GO:0002544 | Biological Process | chronic inflammatory response | IEP | 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 | GO:0045471 | Biological Process | response to ethanol | IEP | GO:0032496 | Biological Process | response to lipopolysaccharide | IEP | GO:0010043 | Biological Process | response to zinc ion | IEP | GO:0042060 | Biological Process | wound healing | IEP | |
SWISS-MODEL Repository : | P50115 |
Sequences : |
MATELEKALSNVIEVYHNYSGIKGNHHALYRDDFRKMVTTECPQFVQNKNTESLFKELDVNSDNAINFEEFLVLVIRVGVAAHKDSHKE |
Function : | S100A8 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 and adhesion. 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. |