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Published on: September 1, 2019
The rapidly expanding CREC protein family: members, localization, function, and role in disease
1Department of Medical Biochemistry, Aarhus University, Aarhus C, Denmark. bh@biokemi.au.dk
Abstract:
Although many aspects of the physiological and pathophysiological mechanisms remain unknown, recent advances in our knowledge suggest that the CREC proteins are promising disease biomarkers or targets for therapeutic intervention in a variety of diseases. The CREC family of low affinity, Ca2+-binding, multiple EF-hand proteins are encoded by five genes, RCN1, RCN2, RCN3, SDF4, and CALU, resulting in reticulocalbin, ER Ca2+-binding protein of 55 kDa (ERC-55), reticulocalbin-3, Ca2+-binding protein of 45 kDa (Cab45), and calumenin. Alternative splicing increases the number of gene products. The proteins are localized in the cytosol, in various parts of the secretory pathway, secreted to the extracellular space or localized on the cell surface. The emerging functions appear to be highly diverse. The proteins interact with several different ligands. Rather well-described functions are attached to calumenin with the inhibition of several proteins in the endoplasmic or sarcoplasmic reticulum membrane, the vitamin K(1) 2,3-epoxide reductase, the gamma-carboxylase, the ryanodine receptor, and the Ca2+-transporting ATPase. Other functions concern participation in the secretory process, chaperone activity, signal transduction as well as participation in a large variety of disease processes.
Insights
The CREC protein family, involved in various cellular functions, shows potential as disease biomarkers and therapeutic targets due to their diverse roles and interactions in multiple diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- The CREC protein family comprises multiple EF-hand calcium-binding proteins encoded by five genes.
- These proteins exhibit diverse cellular localizations, including cytosol, secretory pathway, extracellular space, and cell surface.
- Alternative splicing contributes to a wider range of CREC protein products.
Purpose of the Study:
- To explore the diverse functions and potential applications of CREC proteins.
- To highlight the role of CREC proteins as potential disease biomarkers and therapeutic targets.
Main Methods:
- Literature review of recent advances in CREC protein research.
- Analysis of protein localization, ligand interactions, and functional roles.
Main Results:
- CREC proteins are involved in diverse cellular processes, including secretion, signal transduction, and chaperone activity.
- Calumenin, a CREC protein, inhibits key enzymes like vitamin K(1) 2,3-epoxide reductase and gamma-carboxylase, and ion channels/pumps such as the ryanodine receptor and Ca2+-transporting ATPase.
- CREC proteins interact with various ligands, suggesting broad functional capabilities.
Conclusions:
- CREC proteins are implicated in a wide array of disease processes.
- Their diverse functions and interactions make them promising candidates for disease biomarker development and therapeutic interventions.
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