Search Results
Overview
| Uniprot ID | P05109 |
|---|---|
| Protein Name | Protein S100-A8 |
| Gene Name | S100A8 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 18 | SIIDVYHKYSLIKGN |
| 23 | YHKYSLIKGNFHAVY |
| 36 | VYRDDLKKLLETECP |
| 49 | CPQYIRKKGADVWFK |
| 7 | *MLTELEKALNSIID |
| 85 | MGVAAHKKSHEESHK |
| 92 | KSHEESHKE****** |
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
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Molecular Function | GO:0035662 | Toll-like receptor 4 binding |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005856 | cytoskeleton |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0031012 | extracellular matrix |
| Cellular Component | GO:0005576 | extracellular region |
| Cellular Component | GO:0005615 | extracellular space |
| Cellular Component | GO:0045111 | intermediate filament cytoskeleton |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0005886 | plasma membrane |
| Cellular Component | GO:0034774 | secretory granule lumen |
| Molecular Function | GO:0050544 | arachidonate binding |
| Molecular Function | GO:0005509 | calcium ion binding |
| Molecular Function | GO:0048306 | calcium-dependent protein binding |
| Molecular Function | GO:0008017 | microtubule binding |
| Molecular Function | GO:0050786 | RAGE receptor binding |
| Molecular Function | GO:0008270 | zinc ion binding |
| Biological Process | GO:0006915 | apoptotic process |
| Biological Process | GO:0035425 | autocrine signaling |
| Biological Process | GO:0006914 | autophagy |
| Biological Process | GO:0002544 | chronic inflammatory response |
| Biological Process | GO:0042742 | defense response to bacterium |
| Biological Process | GO:0050832 | defense response to fungus |
| Biological Process | GO:0043542 | endothelial cell migration |
| Biological Process | GO:0006954 | inflammatory response |
| Biological Process | GO:0045087 | innate immune response |
| Biological Process | GO:0002523 | leukocyte migration involved in inflammatory response |
| Biological Process | GO:0070488 | neutrophil aggregation |
| Biological Process | GO:0030593 | neutrophil chemotaxis |
| Biological Process | GO:0018119 | peptidyl-cysteine S-nitrosylation |
| Biological Process | GO:0030307 | positive regulation of cell growth |
| Biological Process | GO:0050729 | positive regulation of inflammatory response |
| Biological Process | GO:2001244 | positive regulation of intrinsic apoptotic signaling pathway |
| Biological Process | GO:0051493 | regulation of cytoskeleton organization |
| Biological Process | GO:0034121 | regulation of toll-like receptor signaling pathway |
| Biological Process | GO:0045471 | response to ethanol |
| Biological Process | GO:0032496 | response to lipopolysaccharide |
| Biological Process | GO:0010043 | response to zinc ion |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.