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S100A9

GeneName

S100A9

Summary

S100A9, also known as p23, p14, or MRP-14, is a 13 kDa calcium-binding protein that is part of the S100 family. It is predominantly expressed in myeloid cells, such as neutrophils and monocytes, and is found in various cellular compartments including the cytoplasm, extracellular space, and plasma membrane. S100A9 is involved in several biological processes, including the regulation of inflammatory responses, leukocyte migration, and antimicrobial activities. Its functions are mediated through interactions with receptors such as RAGE and Toll-like receptors, contributing to cell signalling and immune responses.

Importance

S100A9 is relevant to: - Inflammatory diseases, as it plays a role in the chronic inflammatory response and regulation of immune cell functions. - Cancer research, given its involvement in cell growth regulation and potential roles in tumour progression. - Infectious diseases, due to its antimicrobial properties and involvement in the defense response to bacteria and fungi. - Neurodegenerative diseases, as it influences astrocyte development and neuron projection development, potentially impacting neuroinflammation.

Top Products

For researchers investigating S100A9, we recommend two excellent primary antibodies. The first is the well-cited Anti-S100A9 + Calprotectin (S100A8/A9 complex) antibody [MAC387] (ab22506), which has garnered 96 citations, highlighting its reliability in immunohistochemistry (IHC). This monoclonal antibody is a trusted choice for those studying the S100A9 protein in various contexts. Additionally, we offer the recombinant antibody, Anti-S100A9 antibody [EPR3556] (ab92468). This product has been validated for use in IHC and provides the consistency that comes with recombinant antibodies. With 5 citations, it is gaining traction in the research community as a dependable option for S100A9 detection. Together, these antibodies provide robust tools for your research needs. The Recombinant Human S100A9 Protein ELISA Kit (ab287938) is a reliable option for researchers looking to measure S100A9 levels in their samples, supported by its citation in the literature.

Abcam Product Citation Summary

The data indicates that S100A9 is being studied in various contexts, particularly in relation to tumour biology and liver metastases. The use of multiple applications such as Western blotting and immunohistochemistry highlights the importance of S100A9 in understanding cancer cell behaviour and its potential role in metastasis. Additionally, S100A9 is also being investigated in human samples, suggesting its relevance in clinical settings.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab105472
Mouse
WB
Tumour cell proliferation, migration, and invasion
27086923
ab105472
Mouse
WB, IHC
Liver metastases
27086923
ab17050
Human
IF
Middle ear effusion samples
27078692
ab63818
Human
WB
Differentiated MM6 cells
31231226

Function

S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response (PubMed:12626582, PubMed:15331440, PubMed:16258195, PubMed:19122197, PubMed:20103766, PubMed:21325622, PubMed:8423249). 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 (PubMed:12626582, PubMed:15331440, PubMed:20103766). Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions (PubMed:16258195, PubMed:19122197, PubMed:8423249). 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 (PubMed:15331440, PubMed:21325622). 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 (PubMed:15642721, PubMed:22808130). The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities (PubMed:19534726, PubMed:8423249). Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration (PubMed:15598812, PubMed:21487906). 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) (PubMed:19402754). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade (PubMed:19402754, PubMed:22804476). Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth (PubMed:19087201). 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 (PubMed:19935772). 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 (PubMed:22363402). Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants (PubMed:21912088, PubMed:22489132). Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread (PubMed:16258195). Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3 (PubMed:25417112). The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif (PubMed:25417112).

Post-translational modifications

Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization.

S-nitrosylation of Cys-3 is implicated in LDL(ox)-induced S-nitrosylation of GAPDH at 'Cys-247' through a transnitrosylase mechanism involving a iNOS-S100A8/9 complex (PubMed:25417112).

Methylation at His-105 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8.

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

CAGB, CFAG, MRP14, S100A9, Protein S100-A9, Calgranulin-B, Calprotectin L1H subunit, Leukocyte L1 complex heavy chain, Migration inhibitory factor-related protein 14, S100 calcium-binding protein A9, MRP-14, p14

swissprot:P06702 entrezGene:6280 omim:123886

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