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Details on Person UniProt:P06702 S100A9
| Class:Id | ReferenceGeneProduct:63916 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-114 added on Fri February 6 2015 |
| _displayName | UniProt:P06702 S100A9 |
| _timestamp | 2025-05-21 21:14:52 |
| chain | chain:1-114 |
| checksum | C3BE19729E14C078 |
| comment | 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).SUBUNIT Homodimer (PubMed:11851337, PubMed:16258195). Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9) (PubMed:16258195, PubMed:17553524, PubMed:19087201, PubMed:19122197, PubMed:25417112, PubMed:8423249, PubMed:9083090). S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions (PubMed:19402754). S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions (PubMed:19402754). S100A9 interacts with amyloid-beta protein 40 (PubMed:22457725). Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner (PubMed:11708798). Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes (PubMed:18786929). Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB (PubMed:15642721, PubMed:22808130). Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (PubMed:25417112). Calprotectin (S100A8/9) interacts with CD69 (PubMed:26296369).INTERACTION Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane (PubMed:18786929). Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway (PubMed:15598812).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.PTM Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization.PTM 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).PTM Methylation at His-105 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8.MASS SPECTROMETRY Belongs to the S-100 family. |
| description | recommendedName: Protein S100-A9 alternativeName: Calgranulin-B alternativeName: Calprotectin L1H subunit alternativeName: Leukocyte L1 complex heavy chain alternativeName: fullName evidence="40"Migration inhibitory factor-related protein 14 shortName evidence="40"MRP-14 shortName evidence="39"p14 alternativeName: fullName evidence="36"S100 calcium-binding protein A9 |
| geneName | S100A9 CAGB CFAG MRP14 |
| identifier | P06702 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Antimicrobial Antioxidant Apoptosis Autophagy Calcium Cell membrane Chemotaxis Cytoplasm Cytoskeleton Direct protein sequencing Immunity Inflammatory response Innate immunity Membrane Metal-binding Methylation Phosphoprotein Proteomics identification Reference proteome Repeat S-nitrosylation Secreted Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 |
| name | S100A9 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9002609] ENSEMBL:ENSG00000163220 S100A9 [Homo sapiens] |
| secondaryIdentifier | S10A9_HUMAN D3DV36 Q6FGA1 Q9NYM0 Q9UCJ1 |
| sequenceLength | 114 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:5432857] S100A9 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:6804774] S100A9 [secretory granule lumen] [Homo sapiens] [EntityWithAccessionedSequence:9626869] S100A9 [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P06702 S100A9 (63916)
