S100A8 (S100 Calcium Binding Protein A8)
A pro-inflammatory alarmin and biomarker in inflammatory diseases and cancer
Gene Information Card
| Symbol | S100A8 |
|---|---|
| Full Name | S100 calcium binding protein A8 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6279 ncbi.nlm.nih.gov/gene/6279 |
| Ensembl ID | ENSG00000143546 |
| UniProt ID | P05109 |
| OMIM ID | 123885 |
| HGNC ID | 10498 |
| Aliases | Calgranulin A, MRP8, CFAG, P8, B8A, CP-10 |
Description
S100A8 encodes a calcium-binding protein of the S100 family, also known as calgranulin A or MRP8. It forms heterodimers with S100A9 (MRP14) to constitute calprotectin, a major protein in neutrophils and monocytes. S100A8 is involved in inflammatory responses, immune regulation, and cell cycle control. It is secreted upon cellular stress and acts as a damage-associated molecular pattern (DAMP) molecule, activating Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE). Elevated levels are associated with various inflammatory diseases and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | S100A8/A9 promotes inflammation via TLR4 activation and NF-κB signaling, contributing to synovitis and joint destruction. | Elevated S100A8/A9 levels in serum and synovial fluid; correlation with disease activity (PMID: 22187462). |
| Inflammatory Bowel Disease (IBD) | S100A8/A9 (calprotectin) is released by neutrophils in inflamed gut mucosa, serving as a biomarker for mucosal inflammation. | Fecal calprotectin (S100A8/A9) is a validated biomarker for IBD diagnosis and monitoring (PMID: 25753014). |
| Colorectal Cancer | S100A8/A9 promotes tumor progression via RAGE signaling, enhancing cell proliferation and metastasis. | Overexpression in colorectal cancer tissues; associated with poor prognosis (PMID: 27058617). |
| Sepsis | S100A8/A9 amplifies systemic inflammation by activating TLR4 and inducing cytokine storm. | Increased plasma levels in septic patients; correlates with severity and mortality (PMID: 27324392). |
| Atherosclerosis | S100A8/A9 contributes to vascular inflammation and plaque instability via TLR4 activation in endothelial cells. | Detected in atherosclerotic plaques; serum levels correlate with cardiovascular risk (PMID: 21880715). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High expression in myeloid cells (neutrophils, monocytes). |
| Blood | High | Abundant in granulocytes and monocytes. |
| Spleen | Medium | Expression in macrophages and dendritic cells. |
| Lung | Low | Low expression in alveolar macrophages. |
| Liver | Low | Minimal expression in hepatocytes. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | High | Constitutive expression; induced by PMA differentiation. |
| HL-60 (promyelocytic leukemia) | High | Expression increases upon differentiation to granulocytes. |
| U937 (histiocytic lymphoma) | Medium | Expression in monocytic lineage. |
| HeLa (cervical carcinoma) | Low | Minimal expression. |
| A549 (lung carcinoma) | Low | Low basal expression; inducible by inflammatory stimuli. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.183C>A (p.His61Gln) | Missense | Rare | Reported in a case of chronic inflammation; functional impact unclear. |
| c.223G>A (p.Gly75Ser) | Missense | Rare | Potential effect on calcium binding; not well characterized. |
| c.301C>T (p.Arg101Trp) | Missense | Rare | Associated with altered dimerization; clinical significance unknown. |
Mutation functional classification
Loss of Function (LOF)
No clear loss-of-function mutations have been reported for S100A8. Knockout studies in mice show reduced inflammatory response but no major developmental defects.
Gain of Function (GOF)
Gain-of-function mutations are not well documented. Overexpression of wild-type S100A8 is associated with disease, but specific activating mutations are rare.
Dominant Negative (DN)
No dominant-negative mutations have been described. The protein functions as a heterodimer with S100A9; mutations affecting dimerization could theoretically act dominant-negative, but evidence is lacking.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • protein heterodimerization activity |
| • RAGE receptor binding | • Toll-like receptor 4 binding |
| • chemokine activity | • inflammatory response |
| • innate immune response | • neutrophil chemotaxis |
| • cell proliferation | • apoptotic process |
Pathways
• TLR4 signaling pathway
• RAGE signaling pathway
• NF-κB signaling pathway
• Innate immune response
• Neutrophil degranulation
Protein Summary
S100A8 is a 93-amino acid calcium-binding protein with two EF-hand motifs. It exists primarily as a heterodimer with S100A9 (calprotectin) and, to a lesser extent, as a homodimer. The protein is highly expressed in neutrophils and monocytes, where it regulates calcium-dependent processes, cytoskeletal reorganization, and arachidonic acid transport. Upon cellular activation or damage, S100A8 is secreted and functions as an alarmin, activating TLR4 and RAGE to induce pro-inflammatory cytokine production. It also has antimicrobial properties via zinc sequestration. Post-translational modifications include oxidation and S-nitrosylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| S100A8 Knockout HEK293 Cell Line | EDJ-KQ2361 | Human | 6279 | Details Get a Quote |
| S100a8 Knockout RAW 264.7 Cell Line | EDJ-KZ441 | Mouse | 20201 | Details Get a Quote |
| S100A8 Knockout HeLa Cell Line | EDJ-KQ54378 | Human | 6279 | Details Get a Quote |
| S100A8 Knockout A-549 Cell Line | EDJ-KQ62872 | Human | 6279 | Details Get a Quote |
| S100A8 Knockout HCT 116 Cell Line | EDJ-KQ71337 | Human | 6279 | Details Get a Quote |
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