| Tissue Specificity | Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn's disease, giant cell arteritis, cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers. |
| 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. Participates also in regulatory T-cell differentiation together with CD69. 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. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory 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 pro-inflammatory 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. 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. (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a TLR4-dependent manner. |
| Protein Name | Protein S100-A8Calgranulin-ACalprotectin L1l SubunitCystic Fibrosis AntigenCfagLeukocyte L1 Complex Light ChainMigration Inhibitory Factor-Related Protein 8Mrp-8P8S100 Calcium-Binding Protein A8Urinary Stone Protein Band A |
| Database Links | Reactome: R-HSA-1236974Reactome: R-HSA-166058Reactome: R-HSA-5602498Reactome: R-HSA-5603041Reactome: R-HSA-5668599Reactome: R-HSA-5686938Reactome: R-HSA-6798695Reactome: R-HSA-6799990 |
| Cellular Localisation | SecretedCytoplasmCytoskeletonCell MembranePeripheral Membrane ProteinPredominantly Localized In The CytoplasmUpon Elevation Of The Intracellular Calcium LevelTranslocated From The Cytoplasm To The Cytoskeleton And The Cell MembraneUpon Neutrophil Activation Or Endothelial Adhesion Of MonocytesIs Secreted Via A Microtubule-MediatedAlternative Pathway |
| Alternative Antibody Names | Anti-Protein S100-A8 antibodyAnti-Calgranulin-A antibodyAnti-Calprotectin L1l Subunit antibodyAnti-Cystic Fibrosis Antigen antibodyAnti-Cfag antibodyAnti-Leukocyte L1 Complex Light Chain antibodyAnti-Migration Inhibitory Factor-Related Protein 8 antibodyAnti-Mrp-8 antibodyAnti-P8 antibodyAnti-S100 Calcium-Binding Protein A8 antibodyAnti-Urinary Stone Protein Band A antibodyAnti-S100A8 antibodyAnti-CAGA antibodyAnti-CFAG antibodyAnti-MRP8 antibody |
Information sourced from Uniprot.org
