S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the S100A10 gene in humans and the S100a10 gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells. They regulate a number of cellular processes such as cell cycle progression and differentiation. The S100 protein is implicated in exocytosis and endocytosis by reorganization of F-actin. The p11 protein is linked with the transport of neurotransmitters. Found in the brain of humans and other mammals, it has been implicated in the regulation of mood. In addition, due to its interaction with serotonin-signaling proteins and its correlation with symptoms of mood disorders, p11 is a new potential target for drug therapy.
Gene The S100 gene family, localized in the cytoplasm and nucleus of cells, includes at least 13 members that are located as a cluster on chromosome 1q21. In humans, 19 family members are currently known, with most S100 genes (S100A1 to S100A16). Proteins in the S100 gene family are known to regulate a number of cellular processes, such as cell cycle progression and differentiation.
Structure
The p11 protein can be found as a free monomer, a homodimer, or a heterotetramer composed of a p11 dimer complex with two molecules of annexin II. The homodimer or heterotetramer can, in turn, dimerize through formation of two disulfide bonds (see figure to the left). The p11 monomer is an asymmetric protein composed of four alpha helices. The dimerized form of the protein is created by packing between the H1 and H4 helices in an antiparallel arrangement with the hydrophobic regions residing in the core. The structure of p11 is classified by a pair of the helix-loop-helix motif, also known as the EF-hand-type that recognizes and binds calcium ions. This is common to all known S-100 proteins. The EF-hand types, united by an anti-parallel beta-strand between loops L1 and L3, are located on the same side of the molecule, opposite the N-and C-termini. As a member of the S-100 family, its structure resembles that of the S-100A1 and S-100B proteins. This class of proteins has been implicated in the regulation of cytoskeleton assembly, cytosolic enzymes, and membrane dynamics. P11's involvement with the cytoskeleton may aid the transport of other proteins throughout the cell and to the cell membrane. Unlike other S-100 proteins, the second EF-hand of protein p11 is incapable of binding calcium due to a series of mutations caused by deletions and substitutions. Annexin II, which is attracted to negatively charged phospholipids, binds to p11 at the Ca2+ binding site. In addition, Annexin II has been implicated in membrane-cytoskeleton interactions and in regulations of ion currents and substances across the membrane. P11 and annexin II form a heterotetrameric protein complex that imitates the structure and function of S-100 proteins activated by the binding of calcium. This tetrameric complex is more stable than the p11 dimer, therefore the overexpression of the annexin II gene results in higher levels of p11 protein.
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