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Gene Review

S100A6  -  S100 calcium binding protein A6

Homo sapiens

Synonyms: 2A9, 5B10, CABP, CACY, Calcyclin, ...
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Disease relevance of S100A6


Psychiatry related information on S100A6


High impact information on S100A6

  • Concomitantly, NI increased urine flow rate (V) (2.0 +/- 0.6 to 7.0 +/- 0.9 ml/min; P less than 0.001) and sodium excretion (UNaV) (92 +/- 12 to 191 +/- 15 mu eq/min; P less than 0.001), and decreased PRA (-66 +/- 3%) and plasma aldosterone (-57 +/- 6%) [9].
  • We investigate the model by simulating large-scale motions of four proteins: glutamine-binding protein, S100A6, dihydrofolate reductase, and HIV-1 protease [10].
  • PRA was determined against an HLA-select frozen T-lymphocyte panel using the antiglobulin cytotoxicity technique [11].
  • The use of dithiothreitol to remove IgM alloantibodies resulted in a modest decrease in PRA at 1 month (33.2 +/- 13%) but no change at 3 months (93.0 +/- 3.4%), suggesting the initial humoral response is an IgM alloantibody that switches almost exclusively to IgG by 3 months [11].
  • METHODS AND RESULTS: PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design [12].

Chemical compound and disease context of S100A6


Biological context of S100A6


Anatomical context of S100A6


Associations of S100A6 with chemical compounds

  • Treatment of the cells by thapsigargin, the ionophore A23187, or cyclic ADP-ribose, to increase [Ca2+]i via different pathways, led to relocation of S100A6 and S100A4 but only partially of the nuclear S100A2, as demonstrated by confocal laser scanning microscopy [23].
  • Ca(2+) binding is responsible for a dramatic change in the global shape and charge distribution of the S100A6 dimer, leading to the exposure of two symmetrically positioned target binding sites [24].
  • Among the 13 calcium-binding proteins screened, only one, S100A6, a homodimeric calcium-binding protein able to bind four Zn(2+), appeared to be highly expressed in the SOD1 mutated mice [25].
  • Calcyclin was originally defined as a cDNA clone (2A9) whose cognate RNA is growth-regulated and whose sequence shows strong similarities to the sequences of the S-100 protein, a calcium-binding protein, as well as to a subunit of the major cellular substrate for tyrosine kinase [26].
  • Ca2+ and Zn2+ binding properties of CaCY were examined with respect to the oxidation state of the single Cys residue at position 3 [27].

Physical interactions of S100A6

  • Titration experiments revealed the stoichiometry of one calcyclin monomer binding to each of GAPDH subunits with a binding constant of 10(8) M-1 [28].
  • Among nine Ca(2+)-binding proteins (calcyclin, S-100 proteins, p11, calgizzarin, calvasculin, calmodulin and troponin C) examined, only calcyclin interacted with CAP-50 [29].
  • We have previously shown that the E-box sequence at position -283/-278 of the S100A6 gene promoter interacts with USF transcription factor and contributes to promoter transcriptional activity [30].

Regulatory relationships of S100A6


Other interactions of S100A6

  • Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma [3].
  • RESULTS: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N [4].
  • On the other hand, the association of S100A12 (EN-RAGE) and S100A6 (calcyclin) with membranes is detergent sensitive [34].
  • S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed [35].
  • The overall apo-S100A3 structure resembles the structures of metal-free S100B and S100A6 solution structures [36].

Analytical, diagnostic and therapeutic context of S100A6


  1. S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo. Deloulme, J.C., Assard, N., Mbele, G.O., Mangin, C., Kuwano, R., Baudier, J. J. Biol. Chem. (2000) [Pubmed]
  2. Demonstration of heterodimer formation between S100B and S100A6 in the yeast two-hybrid system and human melanoma. Yang, Q., O'Hanlon, D., Heizmann, C.W., Marks, A. Exp. Cell Res. (1999) [Pubmed]
  3. Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. Maelandsmo, G.M., Flørenes, V.A., Mellingsaeter, T., Hovig, E., Kerbel, R.S., Fodstad, O. Int. J. Cancer (1997) [Pubmed]
  4. Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases. Komatsu, K., Murata, K., Kameyama, M., Ayaki, M., Mukai, M., Ishiguro, S., Miyoshi, J., Tatsuta, M., Inoue, M., Nakamura, H. Oncology (2002) [Pubmed]
  5. Cluster analysis of S100 gene expression and genes correlating to psoriasin (S100A7) expression at different stages of breast cancer development. Carlsson, H., Petersson, S., Enerbäck, C. Int. J. Oncol. (2005) [Pubmed]
  6. Astrocytic calcium/zinc binding protein S100A6 over expression in Alzheimer's disease and in PS1/APP transgenic mice models. Boom, A., Pochet, R., Authelet, M., Pradier, L., Borghgraef, P., Van Leuven, F., Heizmann, C.W., Brion, J.P. Biochim. Biophys. Acta (2004) [Pubmed]
  7. Ultradian oscillations in plasma renin activity: their relationships to meals and sleep stages. Brandenberger, G., Follenius, M., Muzet, A., Ehrhart, J., Schieber, J.P. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  8. Alcohol stimulation of renin release in man: its relation to the hemodynamic, electrolyte, and sympatho-adrenal responses to drinking. Puddey, I.B., Vandongen, R., Beilin, L.J., Rouse, I.L. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  9. Relationship of increased plasma atrial natriuretic factor and renal sodium handling during immersion-induced central hypervolemia in normal humans. Epstein, M., Loutzenhiser, R., Friedland, E., Aceto, R.M., Camargo, M.J., Atlas, S.A. J. Clin. Invest. (1987) [Pubmed]
  10. Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations. Okazaki, K., Koga, N., Takada, S., Onuchic, J.N., Wolynes, P.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery. Shaddy, R.E., Hunter, D.D., Osborn, K.A., Lambert, L.M., Minich, L.L., Hawkins, J.A., McGough, E.C., Fuller, T.C. Circulation (1996) [Pubmed]
  12. Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators. Benedict, C.R., Shelton, B., Johnstone, D.E., Francis, G., Greenberg, B., Konstam, M., Probstfield, J.L., Yusuf, S. Circulation (1996) [Pubmed]
  13. Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer. Rehman, I., Cross, S.S., Catto, J.W., Leiblich, A., Mukherjee, A., Azzouzi, A.R., Leung, H.Y., Hamdy, F.C. Prostate (2005) [Pubmed]
  14. Antibody to S100a6 protein is a sensitive immunohistochemical marker for neurothekeoma. Fullen, D.R., Lowe, L., Su, L.D. J. Cutan. Pathol. (2003) [Pubmed]
  15. Inducible expression of calcyclin, a gene with strong homology to S-100 protein, during neuroblastoma cell differentiation and its prevalent expression in Schwann-like cell lines. Tonini, G.P., Casalaro, A., Cara, A., Di Martino, D. Cancer Res. (1991) [Pubmed]
  16. Effects of bromocriptine on renin, aldosterone, and prolactin responses to posture and metoclopramide in idiopathic edema: possible therapeutic approach. Sowers, J., Catania, R., Paris, J., Tuck, M. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  17. Evidence of endocrine involvement early in the course of human immunodeficiency virus infection. Merenich, J.A., McDermott, M.T., Asp, A.A., Harrison, S.M., Kidd, G.S. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  18. Cloning and characterization of a cDNA encoding a highly conserved, putative calcium binding protein, identified by an anti-prolactin receptor antiserum. Murphy, L.C., Murphy, L.J., Tsuyuki, D., Duckworth, M.L., Shiu, R.P. J. Biol. Chem. (1988) [Pubmed]
  19. Calcium- and cell cycle-dependent association of annexin 11 with the nuclear envelope. Tomas, A., Moss, S.E. J. Biol. Chem. (2003) [Pubmed]
  20. Calcyclin mediates serum response element (SRE) activation by an osteoblastic extracellular cation-sensing mechanism. Tu, Q., Pi, M., Quarles, L.D. J. Bone Miner. Res. (2003) [Pubmed]
  21. 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]
  22. Expression of members of the S100 Ca2+-binding protein family in guinea-pig smooth muscle. Daub, B., Schroeter, M., Pfitzer, G., Ganitkevich, V. Cell Calcium (2003) [Pubmed]
  23. Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation. Mueller, A., Bächi, T., Höchli, M., Schäfer, B.W., Heizmann, C.W. Histochem. Cell Biol. (1999) [Pubmed]
  24. Crystal structures of S100A6 in the Ca(2+)-free and Ca(2+)-bound states: the calcium sensor mechanism of S100 proteins revealed at atomic resolution. Otterbein, L.R., Kordowska, J., Witte-Hoffmann, C., Wang, C.L., Dominguez, R. Structure (Camb.) (2002) [Pubmed]
  25. S100A6, a calcium- and zinc-binding protein, is overexpressed in SOD1 mutant mice, a model for amyotrophic lateral sclerosis. Hoyaux, D., Alao, J., Fuchs, J., Kiss, R., Keller, B., Heizmann, C.W., Pochet, R., Frermann, D. Biochim. Biophys. Acta (2000) [Pubmed]
  26. Structural and functional analysis of a growth-regulated gene, the human calcyclin. Ferrari, S., Calabretta, B., deRiel, J.K., Battini, R., Ghezzo, F., Lauret, E., Griffin, C., Emanuel, B.S., Gurrieri, F., Baserga, R. J. Biol. Chem. (1987) [Pubmed]
  27. Ca2+ and Zn2+ bind to different sites and induce different conformational changes in human calcyclin. Kordowska, J., Stafford, W.F., Wang, C.L. Eur. J. Biochem. (1998) [Pubmed]
  28. Interaction of calcyclin and its cyanogen bromide fragments with annexin II and glyceraldehyde 3-phosphate dehydrogenase. Filipek, A., Wojda, U., Leśniak, W. Int. J. Biochem. Cell Biol. (1995) [Pubmed]
  29. Specific binding of CAP-50 to calcyclin. Minami, H., Tokumitsu, H., Mizutani, A., Watanabe, Y., Watanabe, M., Hidaka, H. FEBS Lett. (1992) [Pubmed]
  30. Binding and functional characteristics of two E-box motifs within the S100A6 (calcyclin) gene promoter. Leśniak, W., Kuźnicki, J. J. Cell. Biochem. (2006) [Pubmed]
  31. Calcyclin (S100A6) expression is stimulated by agents evoking oxidative stress via the antioxidant response element. Leśniak, W., Szczepańska, A., Kuźnicki, J. Biochim. Biophys. Acta (2005) [Pubmed]
  32. Upstream stimulatory factor is involved in the regulation of the human calcyclin (S100A6) gene. Leśniak, W., Jezierska, A., Kuźnicki, J. Biochim. Biophys. Acta (2000) [Pubmed]
  33. Differential effects of phorbol esters on proliferation and calcyclin expression in human endometrial carcinoma cells. Gong, Y., Alkhalaf, B., Murphy, L.J., Murphy, L.C. Cell Growth Differ. (1992) [Pubmed]
  34. The myeloid expressed EF-hand proteins display a diverse pattern of lipid raft association. Nacken, W., Sorg, C., Kerkhoff, C. FEBS Lett. (2004) [Pubmed]
  35. Differential expression of S100 calcium-binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas. Pelc, P., Vanmuylder, N., Lefranc, F., Heizmann, C.W., Hassid, S., Salmon, I., Kiss, R., Louryan, S., Decaestecker, C. Histopathology (2003) [Pubmed]
  36. Metal-free MIRAS phasing: structure of apo-S100A3. Mittl, P.R., Fritz, G., Sargent, D.F., Richmond, T.J., Heizmann, C.W., Grütter, M.G. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
  37. The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Ohuchida, K., Mizumoto, K., Ishikawa, N., Fujii, K., Konomi, H., Nagai, E., Yamaguchi, K., Tsuneyoshi, M., Tanaka, M. Clin. Cancer Res. (2005) [Pubmed]
  38. S100A6 overexpression within astrocytes associated with impaired axons from both ALS mouse model and human patients. Hoyaux, D., Boom, A., Van den Bosch, L., Belot, N., Martin, J.J., Heizmann, C.W., Kiss, R., Pochet, R. J. Neuropathol. Exp. Neurol. (2002) [Pubmed]
  39. Molecular characterization of a novel amplicon at 1q21-q22 frequently observed in human sarcomas. Forus, A., Berner, J.M., Meza-Zepeda, L.A., Saeter, G., Mischke, D., Fodstad, O., Myklebost, O. Br. J. Cancer (1998) [Pubmed]
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