Homo sapiens Protein: S100A9
InnateDB Protein IDBP-102646.5
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol S100A9
Protein Name S100 calcium binding protein A9
Synonyms 60B8AG; CAGB; CFAG; CGLB; L1AG; LIAG; MAC387; MIF; MRP14; NIF; P14;
Species Homo sapiens
Ensembl Protein ENSP00000357727
InnateDB Gene IDBG-102644 (S100A9)
Protein Structure
UniProt Annotation
Function S100A9 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, 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. 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. 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 proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory 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 proinflammatory 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. {ECO:0000269PubMed:12626582, ECO:0000269PubMed:15331440, ECO:0000269PubMed:15598812, ECO:0000269PubMed:15642721, ECO:0000269PubMed:16258195, ECO:0000269PubMed:19087201, ECO:0000269PubMed:19122197, ECO:0000269PubMed:19402754, ECO:0000269PubMed:19534726, ECO:0000269PubMed:19935772, ECO:0000269PubMed:20103766, ECO:0000269PubMed:21325622, ECO:0000269PubMed:21487906, ECO:0000269PubMed:22363402, ECO:0000269PubMed:22804476, ECO:0000269PubMed:22808130, ECO:0000269PubMed:8423249}.
Subcellular Localization Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway.
Disease Associations
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. {ECO:0000269PubMed:15598812, ECO:0000269PubMed:3313057, ECO:0000269PubMed:3405210, ECO:0000269PubMed:8423249, ECO:0000269PubMed:9083090}.
Number of Interactions This gene and/or its encoded proteins are associated with 97 experimentally validated interaction(s) in this database.
Experimentally validated
Total 97 [view]
Protein-Protein 96 [view]
Protein-DNA 1 [view]
Protein-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0004871 signal transducer activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0008017 microtubule binding
GO:0008270 zinc ion binding
GO:0016209 antioxidant activity
GO:0035662 Toll-like receptor 4 binding
GO:0050544 arachidonic acid binding
GO:0050786 RAGE receptor binding
Biological Process
GO:0001816 cytokine production
GO:0002523 leukocyte migration involved in inflammatory response
GO:0002544 chronic inflammatory response
GO:0006914 autophagy
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007267 cell-cell signaling
GO:0010043 response to zinc ion
GO:0030307 positive regulation of cell growth
GO:0030593 neutrophil chemotaxis
GO:0030595 leukocyte chemotaxis
GO:0031532 actin cytoskeleton reorganization
GO:0032119 sequestering of zinc ion
GO:0032496 response to lipopolysaccharide
GO:0032602 chemokine production
GO:0042742 defense response to bacterium
GO:0045087 innate immune response (InnateDB)
GO:0045113 regulation of integrin biosynthetic process
GO:0045471 response to ethanol
GO:0050729 positive regulation of inflammatory response
GO:0050832 defense response to fungus
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051493 regulation of cytoskeleton organization
GO:0070488 neutrophil aggregation
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0070062 extracellular vesicular exosome
Protein Structure and Domains
InterPro IPR002048 EF-hand domain
IPR013787 S100/CaBP-9k-type, calcium binding, subdomain
PFAM PF00036
Post-translational Modifications
SwissProt P06702
PhosphoSite PhosphoSite-P06702
UniProt Splice Variant
Entrez Gene 6280
RefSeq NP_002956
OMIM 123886
HPRD 00472
EMBL AF237581 AF237582 AL591704 BC047681 CH471121 CR542207 CR542224 M21064 M26311 X06233
GenPept AAA36326 AAA68480 AAF62536 AAF62537 AAH47681 CAA29579 CAG47003 CAG47020 CAI19494 EAW53333 EAW53334