Q9CTY5 · MICU3_MOUSE

  • Protein
    Calcium uptake protein 3, mitochondrial
  • Gene
    Micu3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site238Ca2+ 1 (UniProtKB | ChEBI)
Binding site240Ca2+ 1 (UniProtKB | ChEBI)
Binding site242Ca2+ 1 (UniProtKB | ChEBI)
Binding site244Ca2+ 1 (UniProtKB | ChEBI)
Binding site246Ca2+ 1 (UniProtKB | ChEBI)
Binding site249Ca2+ 1 (UniProtKB | ChEBI)
Binding site476Ca2+ 2 (UniProtKB | ChEBI)
Binding site478Ca2+ 2 (UniProtKB | ChEBI)
Binding site480Ca2+ 2 (UniProtKB | ChEBI)
Binding site482Ca2+ 2 (UniProtKB | ChEBI)
Binding site487Ca2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentmitochondrial intermembrane space
Cellular Componentmitochondrion
Cellular Componentuniplex complex
Molecular Functioncalcium ion binding
Molecular Functioncalcium ion sensor activity
Molecular Functionprotein heterodimerization activity
Biological Processcalcium import into the mitochondrion
Biological Processmitochondrial calcium ion homeostasis
Biological Processpositive regulation of neurotransmitter secretion

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Calcium uptake protein 3, mitochondrial
  • Alternative names
    • EF-hand domain-containing family member A2

Gene names

    • Name
      Micu3
    • Synonyms
      Efha2

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9CTY5

Proteomes

Organism-specific databases

Subcellular Location

Note: Recruited to the mitochondrial inner membrane via its association with the uniplex complex.

Keywords

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).

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.

Go to variant viewer

PTM/Processing

Features

Showing features for transit peptide, chain, disulfide bond.

TypeIDPosition(s)Description
Transit peptide1-6Mitochondrion
ChainPRO_00002512317-523Calcium uptake protein 3, mitochondrial
Disulfide bond515Interchain (with C-465 in MICU1)

Keywords

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).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain226-261EF-hand 1
Domain395-430EF-hand 2; degenerate
Domain464-499EF-hand 3

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    523
  • Mass (Da)
    59,810
  • Last updated
    2006-10-03 v2
  • Checksum
    FD8A996423E6A146
MAALRRFLWPPPRLSPALAPQQPFLSPWGRPAGTAPGMSGRPFSCREEDEGAVAEAAWRRRRWGELSIAAAAGGGLVGLVCYQLYGDPRADPSELAAPELEDPPRGRGLLPIPVAAAKETVATGRAITEDLDLYATSRERRFRLFASIECEGQLFMTPYDFILAVTTDEPKFAKTWKSLSKQELSQMLSETPPVWKGSSKLFRNLKERGVISYTEYLFLLCILTKPHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKKNEKRETKGDEEKRAMLRLQLYGYHSPTNSVLKTDAGELVSRSYWDTLRRSTSQALFSDLAERADDITSLVADTTLLVHFFGKKGKAELNFEDFYRFMDNLQTEVLEIEFLSYSNGMNTISEEDFAHILLRYTNVENTSVFLENVRYSISEEKGITFDEFRSFFQFLNNLEDFAIALNMYNFASRSIGQDEFKRAVYVATGLKLSPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHRGFRGYKTVQKYPTFKSCLKKELHSR

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
F6WMX7F6WMX7_MOUSEMicu3262

Sequence caution

The sequence BAB31674.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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