A0A8I6A2H6 · MICU3_RAT

  • Protein
    Calcium uptake protein 3, mitochondrial
  • Gene
    Micu3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Inferred from homology
  • Annotation score
    4/5

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:31862210).
Senses calcium level via its EF-hand domains: compared to MICU1 and MICU2, MICU3 has a higher affinity for calcium (PubMed:31862210).
MICU1 and MICU3 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:31862210).
At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:31862210).
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 (PubMed:31862210).
The high calcium affinity of MICU3 lowers the calcium threshold necessary for calcium permeation through the MCU channel (PubMed:31862210).
The MICU1-MICU3 heterodimer promotes flexibility of neurotransmission in neuronal cells by enhancing mitochondrial calcium uptake in presynapses (PubMed:31862210).
It is also required to increase mitochondrial calcium uptake in skeletal muscle cells, thereby increasing ATP production (By similarity).

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 Componentuniplex complex
Molecular Functioncalcium ion binding
Molecular Functioncalcium ion sensor activity
Molecular Functionprotein heterodimerization activity
Biological Processcalcium import into the mitochondrion
Biological Processcellular response to calcium ion
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

Gene names

    • Name
      Micu3

Organism names

  • Taxonomic identifier
  • Strain
    • Brown Norway
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    A0A8I6A2H6
  • Secondary accessions
    • A0A8I5ZTV9
    • A0A8I6AA12
    • D3ZG95

Proteomes

Organism-specific databases

Subcellular Location

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

Keywords

PTM/Processing

Features

Showing features for transit peptide, chain, disulfide bond.

TypeIDPosition(s)Description
Transit peptide1-6Mitochondrion
ChainPRO_00004604987-523Calcium uptake protein 3, mitochondrial
Disulfide bond515Interchain (with C-465 in MICU1)

Keywords

Proteomic databases

Expression

Gene expression databases

Interaction

Subunit

Heterodimer; disulfide-linked; heterodimerizes with MICU1 (By similarity).
Component of the uniplex complex, composed of MCU, EMRE/SMDT1, MICU1 and MICU3 in a 4:4:1:1 stoichiometry (By similarity).

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region18-48Disordered
Domain225-260EF-hand 1
Domain414-429EF-hand 2; degenerate
Domain463-498EF-hand 3

Domain

EF-hand domains 1 and 3 have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels (By similarity).
EF-hand domain 2 is degenerate (By similarity).

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)
    59,842
  • Last updated
    2022-05-25 v1
  • Checksum
    02E813F438AE3283
MAALRRLLWPPPRLSPTLAPQQPFLSPWGRPAGTAPGMSGRPFSGREEDEGAVAEAAWRRRRWGELSIAAAAGGGLVGLVCYQLYGDPRADPSELVAPELDESPRGRGLLPIPVAAAKETVATGRAVTEDLDLYATSRERRFRLFASIECEGQLFMTPYDFILAVTTDEPKFAKTWKSLSKQELSQMLSETPPVWKGSSKLFRNLKERGVISYTEYLFLLCILTKPHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKKNEKRETKGDEEKRAMLRLQLYGYHSPTNSVLKPDAEELVSRSYWDTLRRSTSQALFSDLAERADDITSLVADTTLLVHFFGKKGKAELNFEDFYRFMDNLQTEVLEIEFLSYSNGMNTISEEDFAHILLRYTNVENTSVFLENVRYSIPEEKGITFDEFRSFFQFLNNLEDFAIALNMYNFASRSIGQDEFKRAVYVATGLKLSPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHRGFRGYKTVQKYPTFKSCLKKELHSR

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0AAK3FFS0A0AAK3FFS0_RATMicu3499
A0AAK3HSM7A0AAK3HSM7_RATMicu3510
A0AAK3H8H3A0AAK3H8H3_RATMicu3486

Keywords

Sequence databases

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp