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S100A8

GeneName

S100A8

Summary

S100A8, also known as MRP8 or S100 calcium binding protein A8, is a low molecular weight protein (11 kDa) that is primarily expressed in myeloid cells, particularly neutrophils and monocytes. It is part of the calprotectin complex and is found in various cellular compartments including the cytoplasm, extracellular region, and plasma membrane. S100A8 plays a role in several biological processes such as the inflammatory response, leukocyte migration, and autophagy. It binds calcium ions and has been shown to interact with receptors such as RAGE and Toll-like receptor 4, facilitating its involvement in innate immune responses and chronic inflammatory conditions.

Importance

S100A8 is relevant to: - Inflammatory diseases, as it is a marker of neutrophil activation and mediates inflammatory responses. - Cancer research, due to its role in tumour microenvironment modulation and potential influence on cancer cell behaviour. - Autoimmune disorders, where it contributes to chronic inflammation and immune dysregulation. - Infectious diseases, as it is involved in the defence response to bacteria and fungi.

Top Products

For researchers investigating S100A8, we highly recommend the top-selling recombinant monoclonal antibody, Anti-S100A8 antibody [EPR3554] (ab92331). This antibody has been validated for use in Western blotting (WB), immunohistochemistry (IHC), and immunoprecipitation (IP), making it a versatile tool for various experimental needs. With 67 citations, it is well-regarded in the research community, reflecting its reliability and effectiveness in S100A8 detection. This product is an excellent choice for those seeking consistent performance in their studies.

Abcam Product Citation Summary

The data indicates that S100A8 is being investigated in various contexts, particularly in cancer research. The use of antibodies in immunohistochemistry highlights its relevance in studying bladder cancer and liver metastases, suggesting a potential role in tumour biology.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab22506
Human
IHC
Bladder cancer tissue
26197470
ab22506
Mouse
IHC
25661015
ab92331
Mouse
WB, IHC
Liver tissue
27086923

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 (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.

(Microbial infection) Upon infection by human coronavirus SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a TLR4-dependent manner.

Sequence Similarities

Belongs to the S-100 family.

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.

Cellular localization

Alternative names

CAGA, CFAG, MRP8, S100A8, Protein S100-A8, Calgranulin-A, Calprotectin L1L subunit, Cystic fibrosis antigen, Leukocyte L1 complex light chain, Migration inhibitory factor-related protein 8, S100 calcium-binding protein A8, Urinary stone protein band A, MRP-8, p8

swissprot:P05109 swissprot:P06702 entrezGene:6279 entrezGene:6280 omim:123886 omim:123885

Other research areas