Micu1
entrez
216001
canonical
uniprot
Q8VCX5
canonical
ensembl
ENSMUSG00000020111
resolver
ensp
ENSMUSP00000020311
resolver
ensp
ENSMUSP00000090166
resolver
ensp
ENSMUSP00000126597
resolver
ensp
ENSMUSP00000205122
resolver
genesymbol
Micu1
resolver
genesymbol_syn
Cbara1
resolver
uniprot
Q8BK07
resolver
uniprot
Q8BL84
resolver
uniprot
Q8R1W0
resolver
uniprot_entry
MICU1_MOUSE
resolver
uniprot_sec
Q8BK07
resolver
uniprot_sec
Q8BL84
resolver
uniprot_sec
Q8R1W0
resolver
amino_acid_sequence
MFRLNTLSALAELAVGSRWYHGASQPTQTKRRLMLVAFLGASAVTASTGLLWKKAHAESPPCVNSKKPDTEDKERNKDSGEVSSREGRAADAAAEPYPEDKKKKRSGFRDRKVMEYENRIRAYSTPDKIFRYFATLKVINEPGETEVFMTPQDFVRSITPNEKQPEHLGLDQYIIKRFDGKKIAQEREKFADEGSIFYSLGECGLISFSDYIFLTTVLSTPQRNFEIAFKMFDLNGDGEVDMEEFEQVQSIIRSQTSMGMRHRDRPTTGNTLKSGLCSALTTYFFGADLKGKLTIKNFLEFQRKLQHDVLKLEFERHDPVDGRISERQFGGMLLAYSGVQSKKLTAMQRQLKKHFKDGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMKQRLMRGLEKPKDMGFTRLMQAMWKCAQETAWDFALPK
uniprot
proteins
function
FUNCTION: Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:24560927, PubMed:27477272, PubMed:36206740). 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:27477272, PubMed:36206740). 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 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:24560927). 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 (By similarity). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (By similarity). {ECO:0000250|UniProtKB:Q9BPX6, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:27477272, ECO:0000269|PubMed:36206740, ECO:0000269|PubMed:37098122}.; FUNCTION: [Isoform 3]: Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (PubMed:27818145). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (PubMed:27818145). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (PubMed:27818145). {ECO:0000269|PubMed:27818145}.
uniprot
proteins
mass_dalton
54353
uniprot
proteins
mutagenesis
MUTAGEN 62; /note="C->A: No effect."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 101..105; /note="KKKKR->QQQQQ: Abolishes interaction with EMRE/SMDT1 without affecting ability to regulate cristae organization."; /evidence="ECO:0000269|PubMed:37098122"; MUTAGEN 124; /note="S->A: Abolished phosphorylation by AKT1; leading to increased stability."; /evidence="ECO:0000269|PubMed:30504268"; MUTAGEN 124; /note="S->D: Mimics phosphorylation; leading to decreased stability."; /evidence="ECO:0000269|PubMed:30504268"; MUTAGEN 203; /note="C->A: No effect."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 233; /note="D->A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-244; A-423 and A-434. Does not affect ability to regulate cristae organization; when associated with A-244; A-423 and A-434."; /evidence="ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:37098122"; MUTAGEN 244; /note="E->A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-423 and A-434. Does not affect ability to regulate cristae organization; when associated with A-233; A-423 and A-434."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 277; /note="C->A: No effect."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 423; /note="D->A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-244 and A-434. Does not affect ability to regulate cristae organization; when associated with A-233; A-244 and A-434."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 434; /note="E->A: Acts as a dominant negative mutant that reduces the mitochondrial Ca(2+) peaks; when associated with A-233; A-244 and A-423. Does not affect ability to regulate cristae organization; A-233; A-244 and A-423."; /evidence="ECO:0000269|PubMed:24560927"; MUTAGEN 440..445; /note="KQRLMR->AQALMA: Decreased interaction with MCU without affecting ability to regulate cristae organization."; /evidence="ECO:0000269|PubMed:37098122"; MUTAGEN 465; /note="C->A: Abolishes interaction with MICU2."; MUTAGEN Q8VCX5-3:237; /note="D->A: Abolished calcium-binding, leading to a dominant-negative mutant that reduces mitochondrial calcium uptake; when associated with K-248, A-427 and K-438."; MUTAGEN Q8VCX5-3:248; /note="E->K: Abolished calcium-binding, leading to a dominant-negative mutant that reduces mitochondrial calcium uptake; when associated with A-237, A-248 and K-438."; MUTAGEN Q8VCX5-3:427; /note="D->A: Abolished calcium-binding, leading to a dominant-negative mutant that reduces mitochondrial calcium uptake; when associated with A-237, K-248 and K-438."; MUTAGEN Q8VCX5-3:438; /note="E->K: Abolished calcium-binding, leading to a dominant-negative mutant that reduces mitochondrial calcium uptake; when associated with A-237, K-248 and A-427.
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-124 by AKT1 impairs its maturation and stability. {ECO:0000269|PubMed:30504268}.; PTM: Asymmetric dimethylation at Arg-457 by PRMT1 decreases the calcium sensitivity of MICU1 by promoting interaction with UCP2. {ECO:0000250|UniProtKB:Q9BPX6}.; PTM: Degraded by YME1L1 when not complexed as homodimer or heterodimer. Not degraded when complexed as homodimer or heterodimer; the presence of the interchain disulfide bond protecting MICU1 from degradation by YME1L1. {ECO:0000250|UniProtKB:Q9BPX6}.
uniprot
proteins
protein_family
MICU1 family
uniprot
proteins
protein_family
MICU1 subfamily
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21685888
uniprot
proteins
pubmed
23409044
uniprot
proteins
pubmed
24560927
uniprot
proteins
pubmed
26956930
uniprot
proteins
pubmed
27477272
uniprot
proteins
pubmed
27818145
uniprot
proteins
pubmed
30504268
uniprot
proteins
pubmed
36206740
uniprot
proteins
pubmed
37098122
uniprot
proteins
pubmed
38018177
uniprot
proteins
sequence_length
477
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:30504268}. Mitochondrion inner membrane {ECO:0000269|PubMed:30504268}. Note=Recruited to the mitochondrial inner membrane by EMRE/SMDT1 (By similarity). Also localizes to mitochondrial cristae junctions (By similarity). {ECO:0000250|UniProtKB:Q9BPX6}.; SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion intermembrane space {ECO:0000305|PubMed:27818145}. Mitochondrion inner membrane {ECO:0000305|PubMed:27818145}.
uniprot
proteins