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Gene Review

S100A1  -  S100 calcium binding protein A1

Homo sapiens

Synonyms: Protein S100-A1, S-100 protein alpha chain, S-100 protein subunit alpha, S100, S100 calcium-binding protein A1, ...
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Disease relevance of S100A1

  • S100A1 reduced S100A4 induced motility and growth in soft agar and metastasis in vivo [1].
  • Our data suggest that S100A1 is directly involved in the transient perioperative myocardial damage caused by ischemia during open heart surgery in humans [2].
  • RESULTS: Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively [3].
  • The expression level of S100A1 proteins was somewhat higher in the connective tissues of normal cases and adenomas with low-grade dysplasia than in adenomas with high-grade dysplasia and cancers [4].
  • These results suggest that S100A1 is involved in the maintenance of the genetic program that defines normal myocardial function and that its downregulation is permissive for the induction of genes that underlie myocardial hypertrophy [5].

Psychiatry related information on S100A1

  • Alzheimer's neurofibrillary tangles (ANT) in the hippocampal area were studied immunohistochemically using antisera against glial fibrillary acidic protein (GFAP) and S-100 protein in 48 patients with or without dementia between 52 and 92 years old [6].
  • Several diseases, including cancer and Alzheimer's disease, are related to a disorder of multifunctional S100 proteins, which are expressed in cell- and tissue-specific manners [7].
  • Specifically, the localization and appearance in development of proteins such as the beta-subunit of S-100, beta-amyloid (A4 protein), superoxide dismutase, and OK-2 are providing the means for better understanding the morphogenesis of the cellular and eventually molecular basis for the mental retardation in Down syndrome [8].
  • This raises the possibility that abnormalities in S100 protein gene dosage at a critical period during development may be responsible for some of the neurologic abnormalities associated with DS [9].
  • 2. Multiple regression models showed that neuropsychological tests accounted for 23% of the variance associated with S-100 AUC release, after partialing out the effects of age and bypass time [10].

High impact information on S100A1

  • We have established an in vitro system for the editing of apo-B mRNA using synthetic RNAs and S100 extracts from rat hepatoma cells [11].
  • Furthermore, minRNA can be released from high molecular weight RNA by a HeLa cell S100 "debranching" extract [12].
  • Upon incubation of these pre-mRNAs in reaction mixtures containing a nuclear extract and a postnuclear fraction (S100), removal of the first intervening sequence and concomitant joining of the first leader to the second leader was observed [13].
  • S-100 protein in human chondrocytes [14].
  • Evidence for the presence of S-100 protein in the glial component of the human enteric nervous system [15].

Chemical compound and disease context of S100A1


Biological context of S100A1

  • Moreover, S100A1 gene transfer decreased elevated intracellular Na+ concentrations to levels detected in nonfailing cardiomyocytes, reversed reactivated fetal gene expression, and restored energy supply in failing cardiomyocytes [21].
  • S100A1, a Ca(2+) binding protein of the EF-hand type, is preferentially expressed in myocardial tissue and has been found to colocalize with the sarcoplasmic reticulum (SR) and the contractile filaments in cardiac tissue [22].
  • Our data suggest that S100A1 effects are cAMP independent because cellular cAMP levels and protein kinase A-dependent phosphorylation of phospholamban were not altered, and carbachol failed to suppress S100A1 actions [22].
  • S100A1 gene transfer resulted in a significant increase of unloaded shortening and isometric contraction in isolated cardiomyocytes and engineered heart tissues, respectively [22].
  • Introducing a synthetic S100A1 peptide model (devoid of EF-hand Ca2+-binding sites) allowed identification of the S100A1 C terminus (amino acids 75-94) and hinge region (amino acids 42-54) to differentially enhance SR Ca2+ release with a nearly 3-fold higher activity of the C terminus [23].

Anatomical context of S100A1

  • Cardiac adenoviral S100A1 gene delivery rescues failing myocardium [21].
  • S100A1 gene transfer to failing cardiomyocytes restored diminished intracellular Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load mechanistically due to increased SR Ca2+ uptake and reduced SR Ca2+ leak [21].
  • Intracoronary adenovirus-mediated S100A1 gene delivery in vivo to the postinfarcted failing rat heart normalized myocardial contractile function and Ca2+ handling, which provided support in a physiological context for results found in myocytes [21].
  • Because S100A1 is known to modulate SR Ca(2+) handling in skeletal muscle, we sought to investigate the specific role of S100A1 in the regulation of myocardial contractility [22].
  • These effects were exclusively based on enhanced SR Ca2+ release as S100A1 influenced neither SR Ca2+ uptake nor myofilament Ca2+ sensitivity/cooperativity in our experimental setting [23].

Associations of S100A1 with chemical compounds

  • Moreover, in Triton-skinned ventricular trabeculae, S100A1 protein significantly decreased myofibrillar Ca(2+) sensitivity ([EC(50%)]) and Ca(2+) cooperativity, whereas maximal isometric force remained unchanged [22].
  • S100A1 equally enhanced caffeine-induced SR Ca2+ release and Ca2+-induced isometric force transients in both muscle preparations in a dose-dependent manner [23].
  • The chaperone activity of S100A1 was antagonized by calmodulin antagonists, such as fluphenazine and prenylamine, that is, indeed an intrinsic function of the protein [24].
  • S100A1 uptake protects neonatal ventricular cardiomyocytes from 2-deoxyglucose and oxidative stress-induced apoptosis in vitro [25].
  • S100A1 binding domain 1 binds the ligand in the presence of 1 mM free [Ca2+] or 1 mM EGTA [26].

Physical interactions of S100A1

  • S100A4 has been shown to interact in vitro with another member of the S100 family of proteins, S100A1 [1].
  • In the reverse experiment, phosphoglucomutase bound to S100A1 and S100B-Sepharose in a calcium-dependent manner [27].
  • Chemical cross-linking, ligand blotting and fluorescence emission spectroscopy reveal that removal of, or mutations within, the sequence encompassing residues 88-90 in the unique C-terminal region of S100A1 interfere with binding to CapZ alpha and to TRTK-12, a synthetic CapZ alpha peptide [28].
  • S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins [29].

Regulatory relationships of S100A1

  • Whereas native and recombinant S100A1 inhibited GFAP assembly, a truncated S100A1 lacking the last six C-terminal residues (Phe88-Ser93) (S100A1Delta88-93) proved unable to do so [30].
  • S100A1 inhibited phosphoglucomutase activity in a calcium-dependent manner [27].
  • These data demonstrate for the first time that S100A1 is differentially expressed in myocardium and that in human cardiomyopathy a reduced expression of S100A1 may contribute to a compromised contractility [31].

Other interactions of S100A1


Analytical, diagnostic and therapeutic context of S100A1


  1. Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes. Wang, G., Zhang, S., Fernig, D.G., Martin-Fernandez, M., Rudland, P.S., Barraclough, R. Oncogene (2005) [Pubmed]
  2. Translocation of S100A1(1) calcium binding protein during heart surgery. Brett, W., Mandinova, A., Remppis, A., Sauder, U., Rüter, F., Heizmann, C.W., Aebi, U., Zerkowski, H.R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  3. Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions. Keijser, S., Missotten, G.S., Bonfrer, J.M., de Wolff-Rouendaal, D., Jager, M.J., de Keizer, R.J. The British journal of ophthalmology. (2006) [Pubmed]
  4. Development and progression of malignancy in human colon tissues are correlated with expression of specific Ca(2+)-binding S100 proteins. Bronckart, Y., Decaestecker, C., Nagy, N., Harper, L., Schäfer, B.W., Salmon, I., Pochet, R., Kiss, R., Heizman, C.W. Histol. Histopathol. (2001) [Pubmed]
  5. The myocardial protein S100A1 plays a role in the maintenance of normal gene expression in the adult heart. Tsoporis, J.N., Marks, A., Zimmer, D.B., McMahon, C., Parker, T.G. Mol. Cell. Biochem. (2003) [Pubmed]
  6. Alzheimer's neurofibrillary tangles are penetrated by astroglial processes and appear eosinophilic in their final stages. Yamaguchi, H., Morimatsu, M., Hirai, S., Takahashi, K. Acta Neuropathol. (1987) [Pubmed]
  7. Up-regulation of S100C in normal human fibroblasts in the process of aging in vitro. Sakaguchi, M., Miyazaki, M., Kondo, T., Namba, M. Exp. Gerontol. (2001) [Pubmed]
  8. Growth and development of the brain in Down syndrome. Becker, L., Mito, T., Takashima, S., Onodera, K. Prog. Clin. Biol. Res. (1991) [Pubmed]
  9. S100 protein and Down syndrome. Marks, A., Allore, R. Bioessays (1990) [Pubmed]
  10. Neuropsychological change and S-100 protein release in 130 unselected patients undergoing cardiac surgery. Kilminster, S., Treasure, T., McMillan, T., Holt, D.W. Stroke (1999) [Pubmed]
  11. An in vitro system for the editing of apolipoprotein B mRNA. Driscoll, D.M., Wynne, J.K., Wallis, S.C., Scott, J. Cell (1989) [Pubmed]
  12. Evidence for trans splicing in trypanosomes. Sutton, R.E., Boothroyd, J.C. Cell (1986) [Pubmed]
  13. Splicing of in vitro synthesized messenger RNA precursors in HeLa cell extracts. Hernandez, N., Keller, W. Cell (1983) [Pubmed]
  14. S-100 protein in human chondrocytes. Stefansson, K., Wollmann, R.L., Moore, B.W., Arnason, B.G. Nature (1982) [Pubmed]
  15. Evidence for the presence of S-100 protein in the glial component of the human enteric nervous system. Ferri, G.L., Probert, L., Cocchia, D., Michetti, F., Marangos, P.J., Polak, J.M. Nature (1982) [Pubmed]
  16. Paragangliomas of the head and neck: immunohistochemical neuroendocrine and intermediate filament typing. Johnson, T.L., Zarbo, R.J., Lloyd, R.V., Crissman, J.D. Mod. Pathol. (1988) [Pubmed]
  17. Immediate early gene IEX-1 induces astrocytic differentiation of U87-MG human glioma cells. You, F., Osawa, Y., Hayashi, S., Nakashima, S. J. Cell. Biochem. (2007) [Pubmed]
  18. Effect of sodium butyrate on S-100 protein levels and the cAMP response. Hirschfeld, A., Bressler, J. J. Cell. Physiol. (1987) [Pubmed]
  19. Hemangioblastoma of the central nervous system: nature of the stromal cells as studied by the immunoperoxidase technique. Tanimura, A., Nakamura, Y., Hachisuka, H., Tanimura, Y., Fukumura, A. Hum. Pathol. (1984) [Pubmed]
  20. Proliferating potential of folliculo-stellate cells in human pituitary adenomas. Immunohistochemical and electron microscopic analysis. Iwaki, T., Kondo, A., Takeshita, I., Nakagaki, H., Kitamura, K., Tateishi, J. Acta Neuropathol. (1986) [Pubmed]
  21. Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. Most, P., Pleger, S.T., Völkers, M., Heidt, B., Boerries, M., Weichenhan, D., Löffler, E., Janssen, P.M., Eckhart, A.D., Martini, J., Williams, M.L., Katus, H.A., Remppis, A., Koch, W.J. J. Clin. Invest. (2004) [Pubmed]
  22. S100A1: a regulator of myocardial contractility. Most, P., Bernotat, J., Ehlermann, P., Pleger, S.T., Reppel, M., Börries, M., Niroomand, F., Pieske, B., Janssen, P.M., Eschenhagen, T., Karczewski, P., Smith, G.L., Koch, W.J., Katus, H.A., Remppis, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  23. The C terminus (amino acids 75-94) and the linker region (amino acids 42-54) of the Ca2+-binding protein S100A1 differentially enhance sarcoplasmic Ca2+ release in murine skinned skeletal muscle fibers. Most, P., Remppis, A., Weber, C., Bernotat, J., Ehlermann, P., Pleger, S.T., Kirsch, W., Weber, M., Uttenweiler, D., Smith, G.L., Katus, H.A., Fink, R.H. J. Biol. Chem. (2003) [Pubmed]
  24. S100A1 is a novel molecular chaperone and a member of the Hsp70/Hsp90 multichaperone complex. Okada, M., Hatakeyama, T., Itoh, H., Tokuta, N., Tokumitsu, H., Kobayashi, R. J. Biol. Chem. (2004) [Pubmed]
  25. Extracellular S100A1 protein inhibits apoptosis in ventricular cardiomyocytes via activation of the extracellular signal-regulated protein kinase 1/2 (ERK1/2). Most, P., Boerries, M., Eicher, C., Schweda, C., Ehlermann, P., Pleger, S.T., Loeffler, E., Koch, W.J., Katus, H.A., Schoenenberger, C.A., Remppis, A. J. Biol. Chem. (2003) [Pubmed]
  26. Interaction of S100A1 with the Ca2+ release channel (ryanodine receptor) of skeletal muscle. Treves, S., Scutari, E., Robert, M., Groh, S., Ottolia, M., Prestipino, G., Ronjat, M., Zorzato, F. Biochemistry (1997) [Pubmed]
  27. Identification of an S100A1/S100B target protein: phosphoglucomutase. Landar, A., Caddell, G., Chessher, J., Zimmer, D.B. Cell Calcium (1996) [Pubmed]
  28. Hydrophobic residues in the C-terminal region of S100A1 are essential for target protein binding but not for dimerization. Osterloh, D., Ivanenkov, V.V., Gerke, V. Cell Calcium (1998) [Pubmed]
  29. Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B. Wilder, P.T., Lin, J., Bair, C.L., Charpentier, T.H., Yang, D., Liriano, M., Varney, K.M., Lee, A., Oppenheim, A.B., Adhya, S., Carrier, F., Weber, D.J. Biochim. Biophys. Acta (2006) [Pubmed]
  30. Role of the C-terminal extension in the interaction of S100A1 with GFAP, tubulin, the S100A1- and S100B-inhibitory peptide, TRTK-12, and a peptide derived from p53, and the S100A1 inhibitory effect on GFAP polymerization. Garbuglia, M., Verzini, M., Rustandi, R.R., Osterloh, D., Weber, D.J., Gerke, V., Donato, R. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  31. Altered expression of the Ca(2+)-binding protein S100A1 in human cardiomyopathy. Remppis, A., Greten, T., Schäfer, B.W., Hunziker, P., Erne, P., Katus, H.A., Heizmann, C.W. Biochim. Biophys. Acta (1996) [Pubmed]
  32. Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1. Wang, G., Rudland, P.S., White, M.R., Barraclough, R. J. Biol. Chem. (2000) [Pubmed]
  33. S100A13. Biochemical characterization and subcellular localization in different cell lines. Ridinger, K., Schäfer, B.W., Durussel, I., Cox, J.A., Heizmann, C.W. J. Biol. Chem. (2000) [Pubmed]
  34. Calcium-dependent interaction of S100B with the C-terminal domain of the tumor suppressor p53. Delphin, C., Ronjat, M., Deloulme, J.C., Garin, G., Debussche, L., Higashimoto, Y., Sakaguchi, K., Baudier, J. J. Biol. Chem. (1999) [Pubmed]
  35. S100A1 increases the gain of excitation-contraction coupling in isolated rabbit ventricular cardiomyocytes. Kettlewell, S., Most, P., Currie, S., Koch, W.J., Smith, G.L. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  36. Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium. Mandinova, A., Atar, D., Schäfer, B.W., Spiess, M., Aebi, U., Heizmann, C.W. J. Cell. Sci. (1998) [Pubmed]
  37. S100A1 codistributes with synapsin I in discrete brain areas and inhibits the F-actin-bundling activity of synapsin I. Benfenati, F., Ferrari, R., Onofri, F., Arcuri, C., Giambanco, I., Donato, R. J. Neurochem. (2004) [Pubmed]
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