S100A5

What is S100A5 protein?

S100A5 (S100 calcium binding protein A5) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q21. S100 calcium binding protein A5, also known as S100A5, is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and 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. S100A5 has a Ca2+ affinity 20- to 100-fold higher than the other S100 proteins studied under identical conditions. This protein also binds Zn2+ and Cu2+, and Cu2+ strongly which impairs the binding of Ca2+. The S100A5 protein is consisted of 92 amino acids and its molecular mass is approximately 10.7 kDa.

What is the function of S100A5 protein?

S100A5 protein is a small calcium-binding protein belonging to the S100 protein family. It is mainly involved in biological processes such as cell cycle progression, cell differentiation and apoptosis, and has a variety of functions. Firstly, S100A5 can regulate cell proliferation and apoptosis, and affect the occurrence and development of tumors. Secondly, it can promote the growth and development of neurons, and has a certain protective effect on neurological diseases such as Parkinson's disease and Alzheimer's disease. In addition, S100A5 is also involved in physiological processes such as inflammatory response, immune regulation, and angiogenesis.

S100A5 Related Signaling Pathway

S100A5 protein is mainly involved in the regulation and signal transduction of intracellular calcium ions. In the cell, S100A5, by binding to calcium ions, can regulate a variety of biological processes, including cell proliferation, differentiation, and apoptosis. There are several specific mechanisms:

As a calcium-binding protein, S100A5 can buffer the fluctuation of intracellular calcium concentration and maintain the stability of intracellular calcium ion level. After binding with calcium ions, S100A5 can further interact with other proteins to transmit or amplify calcium signals; By influencing intracellular calcium levels, S100A5 may be involved in cell cycle regulation.

S100A5 Related Diseases

The S100A5 protein has been implicated in a variety of diseases, especially in the field of oncology. The study found that S100A5 expression is increased in certain malignancies, such as breast cancer, lung cancer, and colorectal cancer, suggesting that it may be involved in tumor occurrence, development, and metastasis. In addition, S100A5 is also associated with a number of other diseases, such as inflammatory diseases, neurological diseases, and so on.

Case Study 1: Ching Chang Cho, 2016

The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia. Here, the researchers found that pentamidine interacts with S100A5 using HSQC titration. They elucidated the interactions of S100A5 with RAGE V domain and pentamidine using fluorescence and NMR spectroscopy. They generated two binary models-the S100A5-RAGE V domain and S100A5-Pentamidine complex-and then observed that the pentamidine and RAGE V domain share a similar binding region in mS100A5. They also used the WST-1 assay to investigate the bioactivity of S100A5, RAGE V domain and pentamidine.

Fig1. Fluorescence emission spectra of RAGE V domain illustrating the changes in the intrinsic tryptophan fluorescence that occur with increasing concentrations of mS100A5 in the micromolar range.

Fig2. SW480 cells were treated with 10 nM mS100A5, 50 nM mS100A5, 100 nM mS100A5, 100 nM mS100A5þ1 mM RAGE V domain, and 100 nM mS100A5 þ1 mM pentamidine.

Case Study 2: B W Schäfer, 2000

S100A5 is a novel member of the EF-hand superfamily of calcium-binding proteins that is poorly characterized at the protein level. Immunohistochemical analysis demonstrates that it is expressed in very restricted regions of the adult brain. Here the researchers characterized the human recombinant S100A5, especially its interaction with Ca(2+), Zn(2+), and Cu(2+). Flow dialysis revealed that the homodimeric S100A5 binds four Ca(2+) ions with strong positive cooperativity and an affinity 20-100-fold higher than the other S100 proteins studied under identical conditions. S100A5 also binds two Zn(2+) ions and four Cu(2+) ions per dimer. Cu(2+) binding strongly impairs the binding of Ca(2+); however, none of these ions change the alpha-helical-rich secondary structure. After covalent labeling of an exposed thiol with 2-(4'-(iodoacetamide)anilino)-naphthalene-6-sulfonic acid, binding of Cu(2+), but not of Ca(2+) or Zn(2+), strongly decreased its fluorescence.

Fig3. expression and purification of human recombinant S100A5.

Fig4. Mass spectrum of rat S100A5 isolated from rat brain tissue.

S100A5 has several biochemical functions, for example, calcium ion binding,copper ion binding,protein homodimerization activity. Some of the functions are cooperated with other proteins, some of the functions could acted by S100A5 itself. We selected most functions S100A5 had, and list some proteins which have the same functions with S100A5. You can find most of the proteins on our site.

S100A5 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with S100A5 here. Most of them are supplied by our site. Hope this information will be useful for your research of S100A5.

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