S100A9
Encyclopedia
Protein S100-A9 also known as migration inhibitory factor-related protein 14 (MRP-14) or calgranulin-B is a protein
that in humans is encoded by the S100A9 gene
.
family of proteins containing 2 EF hand
calcium-binding motifs. S100 proteins are localized in the cytoplasm
and/or nucleus
of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase
.
MRP-14 complexes with MRP-8 (S100A8), another member of the S100 family of calcium-modulated proteins; together, MRP-8 and MRP-14 regulate myeloid cell function by binding to Toll-like receptor-4 (TLR-4
) and the receptor for advanced glycation end products.
.
MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.
MRP-8/14 also regulates vascular insults by controlling neutrophil and macrophage
accumulation, macrophage
cytokine
production, and SMC
proliferation. The above study has shown therefore the deficiency of MRP-8 and MRP-14 reduces neutrophil- and monocyte-dependent vascular inflammation and attenuates the severity of diverse vascular injury responses in vivo. MRP-8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention. Also, the platelet transcriptome reveals quantitative differences between acute and stable coronary artery disease. MRP-14 expression increases before ST-segment-elevation myocardial infarction, (STEMI), and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events.
S100A9 (myeloid-related protein 14, MRP 14 or calgranulin B) has been implicated in the abnormal differentiation of myeloid cells
in the stroma
of cancer. This contributes to creating an overall immunosuppressive microenvironemnt that may contribute to the inability of a protective or therapeutic cellular immune response to be generated by the tumor-bearing host. Outside of malignancy, S100A9 in association with its dimerization partner, S100A8
(MRP8 or calgranulin A) signals for lymphocyte recruitment in sites of inflammation. S100A9/A8 (synonyma: Calgranulin A/B; Calprotectin) are also regarded as marker proteins for a number of inflammatory diseases in humans, especially in rheumatoid arthritis.
has (a mouse mutant, that is deficient of S100A9) been constructed. This mouse is fertile, viable and healthy. However, expression of S100A8 protein, the dimerization partner of S100A9, is also absent in these mice in differentiated myeloid cells. This mouse line has been used to study the role of S100A9 and S100A8 in a number of experimental inflammatory conditions.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the S100A9 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
S100-A9 is a member of the S100S-100 protein
S-100 protein is a family of low molecular weight protein found in vertebrates characterized by two calcium binding sites of the helix-loop-helix conformation. There are at least 21 different types of S100 proteins...
family of proteins containing 2 EF hand
EF hand
The EF hand is a helix-loop-helix structural domain found in a large family of calcium-binding proteins. The EF-hand motif contains a helix-loop-helix topology, much like the spread thumb and forefinger of the human hand, in which the Ca2+ ions are coordinated by ligands within the loop...
calcium-binding motifs. S100 proteins are localized in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
and/or nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase
Casein kinase
Casein kinase is a kinase enzyme.* Casein kinase 1* Casein kinase 2...
.
MRP-14 complexes with MRP-8 (S100A8), another member of the S100 family of calcium-modulated proteins; together, MRP-8 and MRP-14 regulate myeloid cell function by binding to Toll-like receptor-4 (TLR-4
TLR 4
Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR 4 is a toll-like receptor. It detects lipopolysaccharide from Gram-negative bacteria and is thus important in the activation of the innate immune system...
) and the receptor for advanced glycation end products.
Clinical significance
Altered expression of the S100A9 protein is associated with the disease cystic fibrosisCystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
.
MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.
MRP-8/14 also regulates vascular insults by controlling neutrophil and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
accumulation, macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
production, and SMC
SMC protein
SMC proteins represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.-Prokaryotic:...
proliferation. The above study has shown therefore the deficiency of MRP-8 and MRP-14 reduces neutrophil- and monocyte-dependent vascular inflammation and attenuates the severity of diverse vascular injury responses in vivo. MRP-8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention. Also, the platelet transcriptome reveals quantitative differences between acute and stable coronary artery disease. MRP-14 expression increases before ST-segment-elevation myocardial infarction, (STEMI), and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events.
S100A9 (myeloid-related protein 14, MRP 14 or calgranulin B) has been implicated in the abnormal differentiation of myeloid cells
Myelocyte
A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not in circulating blood .-Histology:...
in the stroma
Stroma (animal tissue)
In animal tissue, stroma refers to the connective, supportive framework of a biological cell, tissue, or organ.The stroma in animal tissue is contrasted with the parenchyma.Examples include:* Stroma of iris...
of cancer. This contributes to creating an overall immunosuppressive microenvironemnt that may contribute to the inability of a protective or therapeutic cellular immune response to be generated by the tumor-bearing host. Outside of malignancy, S100A9 in association with its dimerization partner, S100A8
S100 calcium binding protein A8
Protein S100-A8 is a protein that in humans is encoded by the S100A8 gene.-Further reading:...
(MRP8 or calgranulin A) signals for lymphocyte recruitment in sites of inflammation. S100A9/A8 (synonyma: Calgranulin A/B; Calprotectin) are also regarded as marker proteins for a number of inflammatory diseases in humans, especially in rheumatoid arthritis.
Animal studies
A S100A9 knockout mouseKnockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
has (a mouse mutant, that is deficient of S100A9) been constructed. This mouse is fertile, viable and healthy. However, expression of S100A8 protein, the dimerization partner of S100A9, is also absent in these mice in differentiated myeloid cells. This mouse line has been used to study the role of S100A9 and S100A8 in a number of experimental inflammatory conditions.