A0A8I6A2H6 · MICU3_RAT
- ProteinCalcium uptake protein 3, mitochondrial
- GeneMicu3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids523 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
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).
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.
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 | 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 | cellular response to calcium ion | |
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
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionA0A8I6A2H6
- Secondary accessions
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
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_0000460498 | 7-523 | Calcium uptake protein 3, mitochondrial | |||
Sequence: LLWPPPRLSPTLAPQQPFLSPWGRPAGTAPGMSGRPFSGREEDEGAVAEAAWRRRRWGELSIAAAAGGGLVGLVCYQLYGDPRADPSELVAPELDESPRGRGLLPIPVAAAKETVATGRAVTEDLDLYATSRERRFRLFASIECEGQLFMTPYDFILAVTTDEPKFAKTWKSLSKQELSQMLSETPPVWKGSSKLFRNLKERGVISYTEYLFLLCILTKPHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKKNEKRETKGDEEKRAMLRLQLYGYHSPTNSVLKPDAEELVSRSYWDTLRRSTSQALFSDLAERADDITSLVADTTLLVHFFGKKGKAELNFEDFYRFMDNLQTEVLEIEFLSYSNGMNTISEEDFAHILLRYTNVENTSVFLENVRYSIPEEKGITFDEFRSFFQFLNNLEDFAIALNMYNFASRSIGQDEFKRAVYVATGLKLSPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHRGFRGYKTVQKYPTFKSCLKKELHSR | ||||||
Disulfide bond | 515 | Interchain (with C-465 in MICU1) | ||||
Sequence: C |
Keywords
- PTM
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).
Component of the uniplex complex, composed of MCU, EMRE/SMDT1, MICU1 and MICU3 in a 4:4:1:1 stoichiometry (By similarity).
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 18-48 | Disordered | ||||
Sequence: LAPQQPFLSPWGRPAGTAPGMSGRPFSGREE | ||||||
Domain | 225-260 | EF-hand 1 | ||||
Sequence: KPHAGFRIAFNMFDTDGNEMVDKKEFLVLQEIFRKK | ||||||
Domain | 414-429 | EF-hand 2; degenerate | ||||
Sequence: ITFDEFRSFFQFLNNL | ||||||
Domain | 463-498 | EF-hand 3 | ||||
Sequence: LSPHLVNTVFKIFDVDKDDQLSYKEFIGIMKDRLHR |
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).
EF-hand domain 2 is degenerate (By similarity).
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)59,842
- Last updated2022-05-25 v1
- Checksum02E813F438AE3283
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAK3FFS0 | A0AAK3FFS0_RAT | Micu3 | 499 | ||
A0AAK3HSM7 | A0AAK3HSM7_RAT | Micu3 | 510 | ||
A0AAK3H8H3 | A0AAK3H8H3_RAT | Micu3 | 486 |
Keywords
- Technical term