Protein S100-A8 (S100A8)

The protein contains 93 amino acids for an estimated molecular weight of 10835 Da.

 

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. 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 proinflammatory, 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 tow (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 123885

S100 calcium-binding protein a8; s100a8
Cystic fibrosis antigen; cfag
Calgranulin a; caga; cgla
Myeloid-related protein 8; mrp8 s100a8/s100a9 complex, included
Calprotectin, included

DESCRIPTION

Calprotectin, the heterodimeric protein complex composed of S100A8 and S100A9 (123886), 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

Wilson et al. (1975) found a serum protein abnormality in both heterozygotes and homozygotes with cystic fibrosis (CF; 219700). Immunologic quantitation of the protein, called CF antigen, allowed the 3 genotypes to be distinguished (Manson and Brock, 1980; Bullock et al., 1982). Van Heyningen et al. (1985) showed that a protein immunologically indistinguishable from CF antigen is present at high levels in granulocytes from normal and CF persons as well as in myeloid leukemia cells. They studied somatic cell hybrids between a mouse myeloid stem cell line and human myeloid leukemia cells and found that CFAg was expressed only when human chromosome 1 was present. The authors were inclined to think that the accumulated protein was itself the product of the CF gene and that it was altered so that it could not be processed normally; thus, the site of the mutation might be a region of a polypeptide chain that acts as a site for a specific proteolytic cleavage step. Dorin et al. (1987) isolated cDNA clones for CFA from a library constructed with mRNA from chronic myeloid leukemia cells. The complete nucleotide sequence was obtained from the cDNA clone and by primary extension of mRNA. The amino acid sequence, as predicted from the nucleotide sequence, showed significant homology with intestinal and brain calcium-binding proteins. Dorin et al. (1987) concluded that abnormal accumulation of such a protein in CF should be investigated, since there is gathering evidence that the basic defect is in pathways controlling chloride channel activity (Welsh and Liedtke, 1986; Frizzell et al., 1986). Wilkinson et al. (1988) produced monoclonal antibodies specifically recognizing CFAG. Immunoaffinity purification of CFAG from several sources showed 2 components: one of molecular weight 11,000 and one of molecular weight 14,000. Wilkinson et al. (1988) isolated cDNA clones corresponding to each protein. Since the major source of these proteins is neutrophil granulocytes, Wilkinson et al. (1988) suggested the names calgranulin A (CAGA) and B (CAGB; 123886). Both CAGA and CAGB show homology with the calcium-binding protein S100 (S100A1; 176940). Wilkinson et al. (1988) used the monoclonal antibodies to study tissue distribution of the 2 proteins. Strong expression was found in granulocytes and in a restricted subset of normal stratified squamous epithelium, including tongue, esophagus, and buccal cells. Lung, pancreas, and skin, sites where the cystic fibrosis defect is expressed, were not calgranulin-positive. A number of hyperproliferative neoplastic or frankly malignant epithelia were found to express the 2 proteins.

MAPPING

Using somatic cell hybrids containing rearranged human chromosomes, Dorin et al. (1987) localized the CFA gene to 1q12-q22. Using probes for both subunits of the CF-associated antigen, isolated from a chronic myeloid leukemia-derived cDNA library, van Heyningen et al. (1989) and Dorin et al. (1990) confirmed the assignment of CFAG (CAGA) to 1q12-q21 and showed that CAGB cosegregates with it in a panel of somatic cell hybrids. Gross (2014) mapped the S100A ... More on the omim web site

Subscribe to this protein entry history

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 123885 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed