Q9CTY5 · MICU3_MOUSE
- ProteinCalcium uptake protein 3, mitochondrial
- GeneMicu3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids523 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Tissue-specific calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which specifically regulates MCU channel activity in the central nervous system and skeletal muscle (PubMed:38018177).
Senses calcium level via its EF-hand domains: compared to MICU1 and MICU2, MICU3 has a higher affinity for calcium (By similarity).
MICU1 and MICU3 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (By similarity).
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 MICU3 induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU3 heterodimer away from the pore, allowing calcium permeation through the MCU channel (By similarity).
The high calcium affinity of MICU3 lowers the calcium threshold necessary for calcium permeation through the MCU channel (By similarity).
The MICU1-MICU3 heterodimer promotes flexibility of neurotransmission in neuronal cells by enhancing mitochondrial calcium uptake in presynapses (By similarity).
It is also required to increase mitochondrial calcium uptake in skeletal muscle cells, thereby increasing ATP production (PubMed:34845191, PubMed:38018177).
Senses calcium level via its EF-hand domains: compared to MICU1 and MICU2, MICU3 has a higher affinity for calcium (By similarity).
MICU1 and MICU3 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (By similarity).
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 MICU3 induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU3 heterodimer away from the pore, allowing calcium permeation through the MCU channel (By similarity).
The high calcium affinity of MICU3 lowers the calcium threshold necessary for calcium permeation through the MCU channel (By similarity).
The MICU1-MICU3 heterodimer promotes flexibility of neurotransmission in neuronal cells by enhancing mitochondrial calcium uptake in presynapses (By similarity).
It is also required to increase mitochondrial calcium uptake in skeletal muscle cells, thereby increasing ATP production (PubMed:34845191, PubMed:38018177).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 238 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 240 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 242 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 244 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 246 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 249 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 476 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 478 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 480 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 482 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 487 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial intermembrane space | |
Cellular Component | mitochondrion | |
Cellular Component | uniplex complex | |
Molecular Function | calcium ion binding | |
Molecular Function | calcium ion sensor activity | |
Molecular Function | protein heterodimerization activity | |
Biological Process | calcium import into the mitochondrion | |
Biological Process | mitochondrial calcium ion homeostasis | |
Biological Process | positive regulation of neurotransmitter secretion |
Keywords
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCalcium uptake protein 3, mitochondrial
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9CTY5
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Recruited to the mitochondrial inner membrane via its association with the uniplex complex.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice show impaired exercise capacity (PubMed:38018177).
Skeletal muscles display changes in the force response and fatigue, characterized by a significantly increased maximal force of the muscle and an altered fiber type composition with an increase in the ratio of type IIb (low oxidative capacity) to type IIa (high oxidative capacity) fibers (PubMed:38018177).
Skeletal muscles display changes in the force response and fatigue, characterized by a significantly increased maximal force of the muscle and an altered fiber type composition with an increase in the ratio of type IIb (low oxidative capacity) to type IIa (high oxidative capacity) fibers (PubMed:38018177).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 21 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for transit peptide, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-6 | Mitochondrion | ||||
Sequence: MAALRR | ||||||
Chain | PRO_0000251231 | 7-523 | Calcium uptake protein 3, mitochondrial | |||
Sequence: FLWPPPRLSPALAPQQPFLSPWGRPAGTAPGMSGRPFSCREEDEGAVAEAAWRRRRWGELSIAAAAGGGLVGLVCYQLYGDPRADPSELAAPELEDPPRGRGLLPIPVAAAKETVATGRAITEDLDLYATSRERRFRLFASIECEGQLFMTPYDFILAVTTDEPKFAKTWKSLSKQELSQMLSETPPVWKGSSKLFRNLKERGVISYTEYLFLLCILTKPHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKKNEKRETKGDEEKRAMLRLQLYGYHSPTNSVLKTDAGELVSRSYWDTLRRSTSQALFSDLAERADDITSLVADTTLLVHFFGKKGKAELNFEDFYRFMDNLQTEVLEIEFLSYSNGMNTISEEDFAHILLRYTNVENTSVFLENVRYSISEEKGITFDEFRSFFQFLNNLEDFAIALNMYNFASRSIGQDEFKRAVYVATGLKLSPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHRGFRGYKTVQKYPTFKSCLKKELHSR | ||||||
Disulfide bond | 515 | Interchain (with C-465 in MICU1) | ||||
Sequence: C |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Predominantly expressed in skeletal muscle and central nervous system.
Induction
Down-regulated in skeletal muscle from aged mice.
Gene expression databases
Interaction
Subunit
Heterodimer; disulfide-linked; heterodimerizes with MICU1 (PubMed:38018177).
Heterodimerizes with isoform 3 of MICU1 (MICU1.1) in skeletal muscle (PubMed:38018177).
Component of the uniplex complex, composed of MCU, EMRE/SMDT1, MICU1 and MICU3 in a 4:4:1:1 stoichiometry (By similarity).
Heterodimerizes with isoform 3 of MICU1 (MICU1.1) in skeletal muscle (PubMed:38018177).
Component of the uniplex complex, composed of MCU, EMRE/SMDT1, MICU1 and MICU3 in a 4:4:1:1 stoichiometry (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 226-261 | EF-hand 1 | ||||
Sequence: PHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKKN | ||||||
Domain | 395-430 | EF-hand 2; degenerate | ||||
Sequence: ENTSVFLENVRYSISEEKGITFDEFRSFFQFLNNLE | ||||||
Domain | 464-499 | EF-hand 3 | ||||
Sequence: SPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHRG |
Domain
EF-hand domains 1 and 3 have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels. EF-hand domain 2 is degenerate.
Sequence similarities
Belongs to the MICU1 family. MICU3 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length523
- Mass (Da)59,810
- Last updated2006-10-03 v2
- ChecksumFD8A996423E6A146
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6WMX7 | F6WMX7_MOUSE | Micu3 | 262 |
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC102680 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC160537 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK019353 EMBL· GenBank· DDBJ | BAB31674.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |