S100A8

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Product Information
Primary Accession	P05109
Species	Human
Sequence	Ala25-Lys96
Purity	> 95% as analyzed by SDS-PAGE > 95% as analyzed by HPLC
Endotoxin Level	< 1 EU/ µg of protein by gel clotting method
Expression System	E. coli
Formulation	Lyophilized after extensive dialysis against 20 mM Tris-HCl, 1 mM DTT, 0.1 mM EDTA, pH 8.0.
Reconstitution	It is recommended that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Reconstitute the lyophilized powder in ddH₂O at 200 µg/ml.
Storage & Stability	Upon receiving, this product remains stable for up to 6 months at lower than -70°C. Upon reconstitution, the product should be stable for up to 1 week at 4°C or up to 3 months at -20°C. For long term storage it is recommended that a carrier protein (example 0.1% BSA) be added. Avoid repeated freeze-thaw cycles.

Additional Information
Gene ID	6279
Other Names	Protein S100-A8, Calgranulin-A, Calprotectin L1L subunit, Cystic fibrosis antigen, CFAG, Leukocyte L1 complex light chain, Migration inhibitory factor-related protein 8, MRP-8, p8, S100 calcium-binding protein A8, Urinary stone protein band A, S100A8 (HGNC:10498), CAGA, CFAG, MRP8
Target Background	S100 calcium-binding protein A8 (S100A8) is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100A8 protein plays an important role in the regulation of inflammation. It can activate inflammatory cells and cytokines via chemotactic activity for neutrophils, and it can bind to the receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), thus mediating intracellular inflammatory signaling transduction. S100A8 is detected in various human cancers, presenting abundant expression in neoplastic tumor cells as well as infiltrating immune cells. S100A8 exhibits high constitutive expression in neutrophils and activated macrophages, and is also found in epithelial cells under pathological conditions.

Protein Information
Name	S100A8 (HGNC:10498)
Synonyms	CAGA, CFAG, MRP8
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. Also participates in regulatory T-cell differentiation together with CD69 (PubMed:26296369). 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.
Cellular Location	Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway
Tissue Location	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