MICU1

Chr 10q22.1

mitochondrial calcium uptake 1

Aliases:: CALC, EFHA3, FLJ12684
MANE:: ENST00000361114.10

OMIM: 605084 ↗NCBI: 10367 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

MICU1 · Q9BPX6

v62025-08-01

Predicted Aligned Error matrix for MICU1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.1/ 100

Confident

476 residues

Confidence breakdown

Very high(≥ 90)43%
Confident(70–90)30%
Low(50–70)5%
Very low(< 50)22%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Congenital muscular dystrophy
BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders
BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes
BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis

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Disease associations (Open Targets)

proximal myopathy with extrapyramidal signs
0.79
neurodevelopmental disorder
0.43
mitochondrial disease
0.37
inborn mitochondrial metabolism disorder
0.37
hereditary disease
0.34
Abnormality of the nervous system
0.34
ureterolithiasis
0.26
alcohol drinking
0.20
atrial fibrillation
0.20
stroke disorder
0.20

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Calcium uptake protein 1, mitochondrial

Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988, PubMed:28615291, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:34463251, PubMed:36206740, PubMed:37036971, PubMed:37126688). 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:26903221, PubMed:28615291, PubMed:32148862, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:36206740, PubMed:37036971, PubMed:37126688). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:37036971, PubMed:37126688). 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:32494073, PubMed:32667285, PubMed:32762847). 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 (PubMed:30082385, PubMed:30403999). Also acts as a barrier for inhibitors of the MCU channel, such as ruthenium red or its derivative Ru360 (PubMed:37244260). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:31427612, PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733)