Disease relevance of S100A13

• We investigated the expression of S100A13 in human astrocytic gliomas in relation to tumour grading and vascularization [1].
• FGF1 was equally expressed in the vast majority of tumours, whereas S100A13 and VEGF-A were significantly up-regulated in high-grade vascularized gliomas [1].
• In both cases, export is based on the Cu2+-dependent formation of multiprotein complexes containing the S100A13 protein and might involve translocation of the protein across the membrane as a 'molten globule'. FGF1 and IL-1alpha are involved in pathological processes such as restenosis and tumor formation [2].
• FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis [3].
• Human S100A13 was heterologously expressed in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using PEG 3350 as the precipitant [4].

High impact information on S100A13

• Interestingly, although immunohistochemical analysis of control neointimal sections exhibited prominent staining for MAC1, IL-1alpha, S100A13, and the acidic phospholipid phosphatidylserine, similar sections obtained from tetrathiomolybdate-treated animals did not [5].
• These data suggest that S100A13 may be involved in the assembly of the multiprotein aggregate required for the release of FGF1 and that Cu2+ oxidation may be an essential post-translational intracellular modifier of this process [6].
• Using specific antisera against S100A13, high protein expression was detected in follicle cells of thyroid, Leydig cells of testis, and specific cells of brain [7].
• So far, the tissue distribution of S100A13 has not been well characterized [7].
• S100A13. Biochemical characterization and subcellular localization in different cell lines [7].

Biological context of S100A13

• Gene expression analyses in immune system cells supported these findings and indicated that bacterial activation of neutrophils caused upregulation of S100A8, S100A9, and S100A13 [8].
• Since twelve S100 genes are clustered on human chromosome 1q21, we determined the chromosomal localization of the human S100A13 [9].
• Flow dialysis revealed that the homodimeric S100A13 binds four Ca(2+) in two sets of binding sites, both displaying positive cooperativity but of very different affinity [7].
• Indeed, S100A13 is a copper binding protein able to enhance the export of FGF1 in response to stress in vitro and to induce the formation of a multiprotein aggregate responsible for FGF1 release [1].
• Here, we followed the translocation of S100A13 in response to an increase in intracellular calcium levels, as protein translocation has been implicated in assembly of signaling complexes and signaling cascades, and several other S100 proteins are involved in such events [10].

Anatomical context of S100A13

• S100A13 immunoreactivity was also detected in both cells and fibers of the hippocampus at 12 weeks, became slightly stronger at 20 weeks, and then decreased with age [11].
• Here, we show that S100A13 is widely expressed in various types of tissues with a high expression level in thyroid gland [7].
• S100A13 mediates the copper-dependent stress-induced release of IL-1alpha from both human U937 and murine NIH 3T3 cells [12].
• S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro [13].
• Translocation of S100A13 was observed in endothelial cells in response to angiotensin II, and the process was dependent on the classic Golgi-ER pathway [10].

Associations of S100A13 with chemical compounds

• Lastly, tetrathiomolybdate, a Cu2+ chelator, significantly represses in a dose-dependent manner the heat shock-induced release of FGF1 and S100A13 [6].
• Terbium binding and isothermal titration calorimetry data reveal that two atoms of Cu2+/Ca2+ bind per subunit of S100A13 [14].

Other interactions of S100A13

• On the basis of these findings, we speculate that the three anti-allergic drugs might inhibit degranulation by binding with S100A12 and S100A13 [15].
• Moreover, both S100A13 and VEGF-A expression significantly correlated with microvessel density and tumour grading [1].
• S100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells [10].
• S100A13 is a member of the S100 protein family that is involved in the copper-dependent nonclassical secretion of signal peptideless proteins fibroblast growth factor 1 and interleukin 1 lpha [14].
• The human gene maps at the telomeric end of the epidermal differentiation complex (EDC), within chromosomal band 1q21, while the mouse gene maps within the mouse EDC, on mouse chromosome 3, between S100A9 and S100A13 [16].

Analytical, diagnostic and therapeutic context of S100A13

• Results of the isothermal titration calorimetry experiments show that S100A13 can bind independently to both Ca2+ and Cu2+ with almost equal affinity (Kd in the micromolar range) [14].
• Results of the thermal denaturation experiments monitored by far-ultraviolet circular dichroism, limited trypsin digestion, and hydrogen-deuterium exchange (using 1H-15N heteronuclear single quantum coherence spectra) reveal that Ca2+ and Cu2+ have opposite effects on the stability of S100A13 [14].
• Crystallization and preliminary X-ray analysis of human S100A13 [4].

References