Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we report the characterization of a human cDNA coding for the recently published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP, calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is similar to most other S100 genes. It is composed of three exons which are divided by two introns of 900 bp and 400 bp. The protein is encoded by sequences in exons 2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located on human chromosome 1q21 in a clustered organization. Hence, we investigated whether S100A11 (S100C, calgizzarin) and S100A12 are also localized in the S100 gene cluster. We found both genes within the cluster, with S100A11 being close to S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene cluster now is composed of 12 differentially expressed family members.
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PMID:Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21. 898 90

Changes in cytosolic calcium concentrations regulate a wide variety of cellular processes, and calcium-binding proteins are the key molecules in signal transduction, differentiation, and cell cycle control. S100A12, a recently described member of the S100 protein family, has been shown to be coexpressed in granulocytes and monocytes together with two other S100 proteins, MRP8 (S100A8) and MRP14 (S100A9), and a functional relationship between these three S100 proteins has been suggested. Using Western blotting, calcium overlays, intracellular flow cytometry, and cytospin preparations, we demonstrate that S100A12 expression in leukocytes is specifically restricted to granulocytes and that S100A12 represents one of the major calcium-binding proteins in these cells. S100A12, MRP8, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-dependent manner. However, no evidence for direct protein-protein interactions of S100A12 with either MRP8 or MRP14 or the heterodimer was found by chemical cross-linking, density gradient centrifugation, mass spectrometric measurements, or yeast two hybrid detection. Thus, S100A12 acts individually during calcium-dependent signaling, independent of MRP8, MRP14, and the heterodimer MRP8/MRP14. This granulocyte-specific signal transduction pathway may offer attractive targets for therapeutic intervention with exaggerated granulocyte activity in pathological states.
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PMID:S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. 1046 53

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.
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PMID:S100 proteins in Corpora amylacea from normal human brain. 1083 26

MRP-8 and -14 are two S100 proteins highly expressed as a complex by neutrophils, and to a lesser extent by monocytes and certain squamous epithelia. However, less is known about the close homologue S100A12. This S100 protein is expressed by neutrophils and here we show that it is also expressed by monocytes, but not lymphocytes. An absence of coimmunoprecipitation of MRP-14 and S100A12 indicates that S100A12 is not associated with the MRP proteins in vivo. When directly compared to MRP-14, S100A12 expression by squamous epithelia is more restricted. In esophagus and psoriatic skin, S100A12 is differentially regulated, like MRP-14, but the expression pattern of the two S100 proteins is quite different.
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PMID:A comparison of human S100A12 with MRP-14 (S100A9). 1097 13

S100A8, S100A9, and S100A12, collectively known as myeloid-related proteins (MRPs), are highly expressed by the myeloid cell lineage and are found in the extracellular milieu during infections and inflammatory conditions. Recent data showed high levels of MRPs in the serum of HIV type 1 (HIV-1)-infected patients which correlated with disease progression and low CD4(+) counts. Therefore, we set out to investigate the effect of MRPs on HIV-1 replication. We observed a 4- to 5-fold induction of virus production in J1.1, a human T lymphoid cell line latently infected with HIV-1, following treatment with MRPs. Using luciferase-based reporter gene assays, we demonstrated that MRPs induce a dose- and time-dependent activation of the HIV-1 long terminal repeat promoter region that could be blocked by specific anti-MRP polyclonal Abs and by physical denaturation of these proteins. The MRP-mediated induction was acting through the HIV-1 enhancer sequence and was dependent upon NF-kappaB activity. These latter results were also confirmed by EMSA experiments conducted in Jurkat cells and freshly isolated PBMCs. In conclusion, we demonstrate that MRPs induce HIV-1 transcriptional activity and viral replication in infected CD4(+) T-lymphocytes at concentrations similar to those found in the serum of HIV-1-infected patients.
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PMID:HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes. 1221 51

Psoriasis is an inflammatory skin disorder characterised by keratinocyte hyper-proliferation and altered differentiation. To date, linkage analyses have identified at least seven distinct disease susceptibility regions (PSORS1-7). The PSORS4 locus was mapped by our group to chromosome 1q21, within the Epidermal Differentiation Complex. This cluster contains 13 genes encoding S100 calcium-binding proteins, some of which ( S100A7, S100A8 and S100A9) are known to be up-regulated in individual patient keratinocytes. In this study, we analysed S100 gene expression in psoriatic individuals from families characterised by linkage studies. We first selected individuals from two large pedigrees, one of which was linked to the 1q21 locus, whereas the other was unlinked to that region. We studied the expression of 12 S100 genes, by semi-quantitative RT-PCR and Northern blot. These analyses demonstrated up-regulation of S100A8, S100A9 and, to a lesser extent, S100A7 and S100A12, only in the 1q21 linked family. We subsequently analysed S100A7, S100A8, S100 A9 and S100 A12 in three additional samples and were able to confirm S100A8/ S100A9-specific over-expression in 1q-linked pedigrees. Thus, our data provide preliminary evidence for a locus-specific molecular mechanism underlying psoriasis susceptibility.
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PMID:Evidence for differential S100 gene over-expression in psoriatic patients from genetically heterogeneous pedigrees. 1238 71

S100A12 is a member of the S100 family of EF-hand calcium-binding proteins. Together with two other calgranulins, S100A8 and S100A9, it is mostly expressed in human granulocytes, although there is increasing evidence of expression in keratinocytes and psoriatic lesions. It is involved in host-parasite response, and linked to corneal autoimmune diseases connected with filarial parasite infestation. Interaction of S100A12 with a multiligand receptor for advanced glycation end products (RAGE) mediates inflammation. Human recombinant S100A12 was found to induce neuritogenesis of cultured hippocampal cells, similar to two other S100 proteins, S100B and S100A4. X-ray structure of S100A12 has been solved in two crystal forms: R3 and P2(1). In the R3 crystal form S100A12 is a dimer, and in the P2(1) crystal form the dimers are arranged as a hexamer. The hexameric form suggests its role in receptor oligomerisation. S100A12 binds copper at the predicted zinc/copper binding site, which is located close to the surface of the protein. We propose copper-mediated generation of reactive oxygen species by S100A12 as its function in host-parasite response.
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PMID:Multiple structural states of S100A12: A key to its functional diversity. 1264 6

Three members of the S100 family of calcium-binding proteins comprise a new group of proinflammatory molecules released by phagocytes. A novel inflammatory syndrome defined by extraordinarily high expression of S100A8 and S100A9 confirmed recent observations in vitro demonstrating a role of these proteins during recruitment of leukocytes. S100A12 directly activates endothelial cells, mononuclear phagocytes and lymphocytes through interaction with the receptor for advanced glycation end products. Thus, these S100-proteins are attractive targets to modulate inflammation.
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PMID:Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. 1269 38

S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins. Together with S100A8 and S100A9, it belongs to the calgranulin subfamily, i.e. it is mainly expressed in granulocytes, although there is an increasing body of evidence of expression in keratinocytes and psoriatic lesions. As well as being linked to inflammation, allergy and neuritogenesis, S100A12 is involved in host-parasite response, as are the other two calgranulins. Recent data suggest that the function of the S100-family proteins is modulated not only by calcium, but also by other metals such as zinc and copper. Previously, the structure of human S100A12 in low-calcium and high-calcium structural forms, crystallized in space groups R3 and P2(1), respectively, has been reported. Here, the structure of S100A12 in complex with copper (space group P2(1)2(1)2; unit-cell parameters a = 70.6, b = 119.0, c = 90.2 A) refined at 2.19 A resolution is reported. Comparison of anomalous difference electron-density maps calculated with data collected with radiation of wavelengths 1.37 and 1.65 A shows that each monomer binds a single copper ion. The copper binds at an equivalent site to that at which another S100 protein, S100A7, binds zinc. The results suggest that copper binding may be essential for the functional role of S100A12 and probably the other calgranulins in the early immune response.
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PMID:Structure of the human S100A12-copper complex: implications for host-parasite defence. 1277 2

The EF-hand homolog family of S100 proteins comprises the largest group of calcium-binding proteins. Within this S100 family, the phagocyte-specific calcium-binding proteins are pro-inflammatory molecules expressed and secreted by phagocytes, which play a pivotal role within the innate immune system. Although the exact biological functions of these proteins still remain to be defined in greater detail, there is evidence that they are involved in a pro-inflammatory axis associated with various inflammatory conditions. The three members of this group, S100A8, S100A9 and S100A12 are overexpressed at local sites of inflammation. High concentrations are found in synovial fluid, sputum, stool and blood plasma/serum during inflammation. Both the S100A8/S100A9 complex and S100A12 have been proven to be useful as diagnostic markers of inflammation especially in non-infectious inflammatory diseases such as arthritis, chronic inflammatory lung and bowel disease. They indicate phagocyte activation more sensitively than conventional parameters of inflammation. As a consequence, there is a strong correlation to the inflammation of various acute and chronic disorders, making these proteins sensitive parameters for the monitoring of disease activity and response to treatment in individual patients. The phagocyte-specific S100 proteins are able to indicate minimal residual inflammation, which is not detected by other diagnostic tests, and they may even be prospective markers for the outcome of patients. In this review, pro-inflammatory functions of S100 proteins and their usefulness as biomarkers of inflammation are presented.
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PMID:Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. 1514 69


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