Search Results
Overview
| Uniprot ID | P06702 |
|---|---|
| Protein Name | Protein S100-A9 |
| Gene Name | S100A9 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 106 | EGPGHHHKPGLGEGT |
| 38 | TLNQGEFKELVRKDL |
| 4 | ****MTCKMSQLERN |
| 43 | EFKELVRKDLQNFLK |
| 50 | KDLQNFLKKENKNEK |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| 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:0016209 | antioxidant activity |
| 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:0035662 | Toll-like receptor 4 binding |
| Molecular Function | GO:0008270 | zinc ion binding |
| Biological Process | GO:0061844 | antimicrobial humoral immune response mediated by antimicrobial peptide |
| Biological Process | GO:0006915 | apoptotic process |
| Biological Process | GO:0014002 | astrocyte development |
| Biological Process | GO:0035425 | autocrine signaling |
| Biological Process | GO:0006914 | autophagy |
| Biological Process | GO:0007267 | cell-cell signaling |
| 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:0035606 | peptidyl-cysteine S-trans-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:0010976 | positive regulation of neuron projection development |
| Biological Process | GO:0051493 | regulation of cytoskeleton organization |
| Biological Process | GO:0060264 | regulation of respiratory burst involved in inflammatory response |
| Biological Process | GO:0034121 | regulation of toll-like receptor signaling pathway |
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.