Protein S100-A9 (S100A9)
The protein contains 114 amino acids for an estimated molecular weight of 13242 Da.
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:20103766, PubMed:8423249, PubMed:16258195, PubMed:19122197, PubMed:21325622). 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:8423249, PubMed:16258195, PubMed:19122197). 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). 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 proinflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities (PubMed:8423249, PubMed:19534726). Its proinflammatory activity includes recruitment of leukocytes, pro (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| empty |
Biological Process
Actin cytoskeleton reorganization
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Antimicrobial humoral immune response mediated by antimicrobial peptide
Antimicrobial humoral response
Apoptotic process
Astrocyte development
Autocrine signaling
Autophagy
Cell-cell signaling
Chemokine production
Chronic inflammatory response
Cytokine production
Defense response to bacterium
Defense response to fungus
Inflammatory response
Innate immune response
Leukocyte migration involved in inflammatory response
Modulation of process of other organism
Neutrophil aggregation
Neutrophil chemotaxis
Neutrophil degranulation
Peptidyl-cysteine S-nitrosylation
Peptidyl-cysteine S-trans-nitrosylation
Positive regulation of blood coagulation
Positive regulation of cell growth
Positive regulation of inflammatory response
Positive regulation of intrinsic apoptotic signaling pathway
Positive regulation of neuron projection development
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of peptide secretion
Regulation of cytoskeleton organization
Regulation of integrin biosynthetic process
Regulation of translation
Response to ethanol
Response to lipopolysaccharide
Response to zinc ion
Sequestering of zinc ion
Signal transduction
Toll-like receptor signaling pathway
The reference OMIM entry for this protein is 123886
S100 calcium-binding protein a9; s100a9
Cystic fibrosis antigen b
Calgranulin b; cagb; cglb
Myeloid-related protein 14; mrp14 s100a9/s100a8 complex, included
Calprotectin, included
DESCRIPTION
Calprotectin, the heterodimeric protein complex composed of S100A8 (123885) and S100A9, is a major calcium- and zinc-binding protein in the cytosol of neutrophils, monocytes, and keratinocytes (Sampson et al., 2002). Vogl et al. (2007) noted that complexes of S100A8 and S100A9 are the physiologically relevant forms of these proteins.CLONING
See 123885 for a description of calgranulin A (CAGA) and calgranulin B (CAGB), which have molecular weights 11,000 and 14,000, respectively, and together represent the cystic fibrosis antigen (CFAG). They are coded by separate genes. Odink et al. (1987) identified and cloned the calgranulin B gene, CAGB, also known as MRP14.MAPPING
Gross (2014) mapped the S100A9 gene to chromosome 1q21.3 based on an alignment of the S100A9 sequence (GenBank GENBANK AF237581) with the genomic sequence (GRCh38).GENE FUNCTION
By study of DNA from a panel of somatic cell hybrids, van Heyningen et al. (1989) and Dorin et al. (1990) showed that the CAGB gene cosegregates with CAGA (S100A8; 123885) in somatic cell hybrids and that both are closely situated to calcyclin (S100A6; 114110) and calcium placental protein (S100A4; 114210). Psoriasis (see 177900) is an inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Linkage analyses have identified at least 7 distinct disease susceptibility regions. PSORS4 (603935) maps to chromosome 1q21, within the epidermal differentiation complex (EDC; see 152445), a cluster that contains 13 genes encoding S100 calcium-binding proteins. Semprini et al. (2002) analyzed S100 gene expression in psoriatic individuals from 2 large pedigrees characterized by linkage studies, 1 linked and 1 unlinked to the 1q21 locus. The analyses demonstrated that only the 1q21-linked family had upregulation of S100A8, S100A9, and, to a lesser extent, S100A7 (600353) and S100A12 (603112). Later studies confirmed S100A8/S100A9-specific overexpression in 1q-linked pedigrees. Vogl et al. (2007) demonstrated that mice lacking Mrp8-Mrp14 complexes are protected from endotoxin-induced lethal shock and Escherichia coli-induced abdominal sepsis. Both proteins are released during activation of phagocytes, and Mrp8-Mrp14 complexes amplify the endotoxin-triggered inflammatory responses of phagocytes. Mrp8 is the active component that induces intracellular translocation of myeloid differentiation primary response protein-88 (MYD88; 602170) and activation of interleukin-1 receptor-associated kinase-1 (IRAK1; 300283) and nuclear factor-kappa-B (NFKB; see 164011), resulting in elevated expression of tumor necrosis factor-alpha (TNF-alpha; 191160). Using phagocytes expressing a nonfunctional Toll-like receptor-4 (TLR4; 603030), HEK293 cells transfected with TLR4, CD14 (158120), and MD2 (LY96; 605243), and by surface plasmon resonance studies in vitro, Vogl et al. (2007) demonstrated that MRP8 specifically interacts with the TLR4-MD2 complex, thus representing an endogenous ligand of TLR4. The data demonstrated that MRP8 is the active component of the complex, while MRP14 seems to regulate MRP8 function. Vogl et al. (2007) concluded that MRP8-MRP14 complexes are novel inflammatory components that amplify phagocyte activation during sepsis upstream of TNF-alpha-dependent effects. Corbin et al. (2008) found that neutrophil-derived calprotectin inhibited growth of Staphylococcus aureus in abscesses through chelation of Mn( ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 123886 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed