UniprotKB/SwissProt ID: Q8VCX5 (Q8VCX5)
Gene Name:
Micu1
Organism: Mus musculus (Mouse)
Function: Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:24560927, PubMed:27477272, PubMed:36206740). MICU1 and MICU2 (or MICU3) form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927, PubMed:27477272, PubMed:36206740). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (By similarity). At higher calcium levels, calcium-binding to MICU1 and MICU2 (or MICU3) induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU2 heterodimer away from the pore, allowing calcium permeation through the MCU channel (PubMed:24560927). Also required to protect against manganese toxicity by preventing manganese uptake by MCU: mechanistically, manganese-binding to its EF-hand domains does not induce any conformational change, maintaining MCU pore occlusion (By similarity). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (By similarity) Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (PubMed:27818145). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (PubMed:27818145). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (PubMed:27818145)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Mitochondrion intermembrane space. Mitochondrion inner membrane. Mitochondrion intermembrane space. Mitochondrion inner membrane
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