S100A6 Protein—Expression and Function in Norm and Pathology

Abstract

S100A6, also known as calcyclin, is a calcium-binding protein belonging to the S100 protein family. It was first identified and purified more than 30 years ago. Initial structural studies, focused mostly on the mode and affinity of Ca2+ binding and resolution of the resultant conformational changes, were soon complemented by research on its expression, localization and identification of binding partners. With time, the use of biophysical methods helped to resolve the structure and versatility of S100A6 complexes with some of its ligands. Meanwhile, it became clear that S100A6 expression was altered in various pathological states and correlated with the stage/progression of many diseases, including cancers, indicative of its important, and possibly causative, role in some of these diseases. This, in turn, prompted researchers to look for the mechanism of S100A6 action and to identify the intermediary signaling pathways and effectors. After all these years, our knowledge on various aspects of S100A6 biology is robust but still incomplete. The list of S100A6 ligands is growing all the time, as is our understanding of the physiological importance of these interactions. The present review summarizes available data concerning S100A6 expression/localization, interaction with intracellular and extracellular targets, involvement in Ca2+-dependent cellular processes and association with various pathologies.

A Pilot Study of a Panel of Ocular Inflammation Biomarkers in Patients with Primary Sjögren’s Syndrome

“…Here we detected an increase in S100A6 expression in the tears of patients with RA-SS relative to the concentration of this protein in healthy subjects. S100A6 has been demonstrated to fulfill a role in other inflammatory autoimmune diseases such as primary biliary cholangitis and systemic sclerosis of the lung [ 66 ], consistent with our observations. Other than S100A6, S100A8/9/calprotectin has also been studied in inflammatory diseases, especially in RA, confirming the influence of this protein family in the pathology [ 67 , 68 ].…”

Interaction of S100A6 Protein with the Four-Helical Cytokines

“…To explore this possibility, in this work, we test the affinity of another promiscuous S100 oncoprotein [ 50 , 51 ], S100A6 (also known as calcyclin; it has a pairwise sequence identity to S100P of 35% [ 52 , 53 ]), specific to the six four-helical cytokines shown in Table 1 , to 35 four-helical cytokines from all their structural families ( Table S1 ). Our findings greatly expand the long list of known extracellular target proteins of S100A6, which may be of value for deciphering its role in the progression of many cancers, neurodegenerative disorders, myocardial infarction, acute coronary syndrome, chronic renal disease, primary biliary cholangitis, pulmonary fibrosis, systemic sclerosis of the lung, endometriosis, osteoarthritis, various eye pathologies, and other disorders (reviewed in [ 54 , 55 , 56 ]).…”

Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis

“…Of the 117 serum differential proteins we identified, many have been corroborated in epilepsy patients and animal models. S100A6 (calcineurin) is an EF-hand calcium-binding protein that is thought to have multiple functions, including calcium homeostasis and neuronal degeneration (22). One study based on an epileptic rat model showed that S100A6 protein levels were significantly elevated in the cortex and hippocampal CA1 region on day 14 after amygdala stimulation (23).…”