MICU1
entrez
10367
canonical
uniprot
Q9BPX6
canonical
ensembl
ENSG00000107745
resolver
ensp
ENSP00000354415
resolver
ensp
ENSP00000381747
resolver
ensp
ENSP00000402470
resolver
ensp
ENSP00000493232
resolver
ensp
ENSP00000568031
resolver
ensp
ENSP00000568032
resolver
ensp
ENSP00000568033
resolver
ensp
ENSP00000568034
resolver
ensp
ENSP00000568035
resolver
ensp
ENSP00000568036
resolver
ensp
ENSP00000568039
resolver
ensp
ENSP00000568042
resolver
ensp
ENSP00000634263
resolver
ensp
ENSP00000634269
resolver
enst
ENST00000642044
resolver
genesymbol
MICU1
resolver
genesymbol_syn
CALC
resolver
genesymbol_syn
CBARA1
resolver
hgnc
HGNC:1530
resolver
uniprot
A0A0U1RRK1
resolver
uniprot
A0A286YF11
resolver
uniprot
A8MV96
resolver
uniprot
B3KN20
resolver
uniprot
B4DJH9
resolver
uniprot
B4DPI1
resolver
uniprot
B5MBY3
resolver
uniprot
D3YTJ3
resolver
uniprot
O75785
resolver
uniprot
Q9H9N6
resolver
uniprot
Q9UFX0
resolver
uniprot_entry
A0A286YF11_HUMAN
resolver
uniprot_entry
MICU1_HUMAN
resolver
uniprot_sec
A0A0U1RRK1
resolver
uniprot_sec
A8MV96
resolver
uniprot_sec
B3KN20
resolver
uniprot_sec
B4DJH9
resolver
uniprot_sec
B4DPI1
resolver
uniprot_sec
B5MBY3
resolver
uniprot_sec
D3YTJ3
resolver
uniprot_sec
O75785
resolver
uniprot_sec
Q9H9N6
resolver
uniprot_sec
Q9UFX0
resolver
activity_regulation
ACTIVITY REGULATION: Activated by spermine, kaempferol and SB202190, which bind MICU1 and prevent MCU pore occlusion in absence of calcium. {ECO:0000269|PubMed:37244260}.
uniprot
proteins
amino_acid_sequence
MFRLNSLSALAELAVGSRWYHGGSQPIQIRRRLMMVAFLGASAVTASTGLLWKRAHAESPPCVDNLKSDIGDKGKNKDEGDVCNHEKKTADLAPHPEEKKKKRSGFRDRKVMEYENRIRAYSTPDKIFRYFATLKVISEPGEAEVFMTPEDFVRSITPNEKQPEHLGLDQYIIKRFDGKKISQEREKFADEGSIFYTLGECGLISFSDYIFLTTVLSTPQRNFEIAFKMFDLNGDGEVDMEEFEQVQSIIRSQTSMGMRHRDRPTTGNTLKSGLCSALTTYFFGADLKGKLTIKNFLEFQRKLQHDVLKLEFERHDPVDGRITERQFGGMLLAYSGVQSKKLTAMQRQLKKHFKEGKGLTFQEVENFFTFLKNINDVDTALSFYHMAGASLDKVTMQQVARTVAKVELSDHVCDVVFALFDCDGNGELSNKEFVSIMKQRLMRGLEKPKDMGFTRLMQAMWKCAQETAWDFALPKQ
uniprot
proteins
disease_involvement
DISEASE: Myopathy with extrapyramidal signs (MPXPS) [MIM:615673]: An autosomal recessive disorder characterized by early-onset proximal muscle weakness with a static course and moderately to grossly elevated serum creatine kinase levels accompanied by learning difficulties. Most patients develop subtle extrapyramidal motor signs that progress to a debilitating disorder of involuntary movement with variable features, including chorea, tremor, dystonic posturing and orofacial dyskinesia. Additional variable features include ataxia, microcephaly, ophthalmoplegia, ptosis, optic atrophy and axonal peripheral neuropathy. {ECO:0000269|PubMed:24336167, ECO:0000269|PubMed:32395406, ECO:0000269|PubMed:33428302, ECO:0000269|PubMed:33969448}. Note=The disease is caused by variants affecting the gene represented in this entry. The complex phenotype is due to alterations in mitochondrial calcium signaling characterized by increased mitochondrial Ca(2+) load (PubMed:24336167). {ECO:0000269|PubMed:24336167}.; DISEASE: Note=An homozygous partial MICU1 deletion is responsible for a disorder manifesting in childhood with fatigue, lethargy and muscle weakness. The disease is caused by variants affecting the gene represented in this entry. {ECO:0000269|PubMed:27123478}.
uniprot
proteins
function
FUNCTION: Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988, PubMed:28615291, PubMed:30454562, PubMed:30638448, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:34463251, PubMed:36206740, PubMed:37036971, PubMed:37126688). 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:26903221, PubMed:28615291, PubMed:32148862, PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:32790952, PubMed:36206740, PubMed:37036971, PubMed:37126688). At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake (PubMed:32494073, PubMed:32667285, PubMed:32762847, PubMed:37036971, PubMed:37126688). 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:32494073, PubMed:32667285, PubMed:32762847). 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 (PubMed:30082385, PubMed:30403999). Also acts as a barrier for inhibitors of the MCU channel, such as ruthenium red or its derivative Ru360 (PubMed:37244260). Acts as a regulator of mitochondrial cristae structure independently of its ability to regulate the mitochondrial calcium uniporter channel (PubMed:31427612, PubMed:37098122). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733). {ECO:0000269|PubMed:16002733, ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:22904319, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24313810, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26903221, ECO:0000269|PubMed:27099988, ECO:0000269|PubMed:28615291, ECO:0000269|PubMed:30082385, ECO:0000269|PubMed:30403999, ECO:0000269|PubMed:30454562, ECO:0000269|PubMed:30638448, ECO:0000269|PubMed:31427612, ECO:0000269|PubMed:32148862, ECO:0000269|PubMed:32494073, ECO:0000269|PubMed:32667285, ECO:0000269|PubMed:32762847, ECO:0000269|PubMed:32790952, ECO:0000269|PubMed:34463251, ECO:0000269|PubMed:36206740, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37098122, ECO:0000269|PubMed:37126688, ECO:0000269|PubMed:37244260}.; FUNCTION: [Isoform 6]: Isoform that regulates mitochondrial calcium uniporter (MCU) in the skeletal muscle (By similarity). Compared to other isoforms, this isoform has higher affinity for calcium, promoting mitochondrial calcium uptake at lower calcium concentrations (By similarity). This allows a rapid response of mitochondrial metabolism and ensures sustained ATP production needed for resistance and strenuous exercise (By similarity). {ECO:0000250|UniProtKB:Q8VCX5}.
uniprot
proteins
mass_dalton
54351
uniprot
proteins
mutagenesis
MUTAGEN 99..103; /note="KKKKR->AAAAA: Abolishes interaction with EMRE/SMDT1."; /evidence="ECO:0000269|PubMed:30454562, ECO:0000269|PubMed:32790952"; MUTAGEN 99..102; /note="KKKK->EQEQ: Abolishes interaction with EMRE/SMDT1 while maintaining interaction with MICU2."; /evidence="ECO:0000269|PubMed:27099988"; MUTAGEN 106; /note="F->A: Slightly decreased ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32667285"; MUTAGEN 114; /note="Y->A: Decreased ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32494073"; MUTAGEN 117; /note="R->A: Slightly decreased ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32667285"; MUTAGEN 119; /note="R->E: Impaired interaction with MCU."; /evidence="ECO:0000269|PubMed:30638448"; MUTAGEN 119; /note="R->K: Does not affect interaction with MCU."; /evidence="ECO:0000269|PubMed:30638448"; MUTAGEN 121; /note="Y->A: Decreased ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32494073, ECO:0000269|PubMed:32667285"; MUTAGEN 126..129; /note="Missing: Abolished ability to inhibit MCU channel activity in absence of calcium; when associated with 259-E--E-263."; /evidence="ECO:0000269|PubMed:32494073"; MUTAGEN 126; /note="K->A: Abolished ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32667285"; MUTAGEN 126; /note="K->E: Abolished ability to inhibit MCU in absence of calcium."; /evidence="ECO:0000269|PubMed:37036971"; MUTAGEN 129; /note="R->A: Decreased ability to inhibit MCU channel activity in absence of calcium."; /evidence="ECO:0000269|PubMed:32667285"; MUTAGEN 154; /note="R->K: Does not affect interaction with MCU."; /evidence="ECO:0000269|PubMed:30638448"; MUTAGEN 154; /note="R->Q: Impaired interaction with MCU."; /evidence="ECO:0000269|PubMed:30638448"; MUTAGEN 221; /note="R->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:24514027"; MUTAGEN 231; /note="D->A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-242; A-421 and A-432."; /evidence="ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37126688"; MUTAGEN 242; /note="E->A,K: Abolishes mitochondrial Ca(2+) uptake; when associated with A-231; A-421 and A-432."; /evidence="ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37126688"; MUTAGEN 253; /note="Q->A: Does not affect interaction with MICU2 in presence of calcium; decreased interaction with MICU2 in absence of calcium."; /evidence="ECO:0000269|PubMed:32790952"; MUTAGEN 259..263; /note="RHRDR->EHEDE: Abolished ability to inhibit MCU channel activity in absence of calcium; when associated with 126-E--E-129."; /evidence="ECO:0000269|PubMed:32494073"; MUTAGEN 376; /note="D->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:24514027"; MUTAGEN 383..385; /note="FYH->AYA: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:24514027"; MUTAGEN 383; /note="F->A: Abolished interaction with MICU2."; /evidence="ECO:0000269|PubMed:31397067"; MUTAGEN 398; /note="Q->A: Does not affect interaction with MICU2 in absence or presence of calcium."; /evidence="ECO:0000269|PubMed:32790952"; MUTAGEN 421; /note="D->A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-231; A-242 and A-432."; /evidence="ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37126688"; MUTAGEN 427; /note="E->A: Does not affect interaction with MICU2 in presence of calcium; decreased interaction with MICU2 in absence of calcium."; /evidence="ECO:0000269|PubMed:32790952"; MUTAGEN 432; /note="E->A: Abolishes mitochondrial Ca(2+) uptake; when associated with A-231; A-242 and A-421."; /evidence="ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:37036971, ECO:0000269|PubMed:37126688"; MUTAGEN 432; /note="E->K: Loss of function; when associated with A-421."; /evidence="ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:24503055"; MUTAGEN 440..445; /note="RLMRGL->AQALMA: Decreased interaction with MCU."; /evidence="ECO:0000269|PubMed:30454562"; MUTAGEN 455; /note="R->R,F: Abolished methylation by PRMT1."; /evidence="ECO:0000269|PubMed:27642082"; MUTAGEN 463; /note="C->A: Abolishes interchain disulfide bond and heterodimer formation with MICU2."; /evidence="ECO:0000269|PubMed:26387864"; MUTAGEN 463; /note="C->R: Increased degradation by YME1L1."; /evidence="ECO:0000269|PubMed:36206740
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-122 by AKT1 impairs its maturation and stability. {ECO:0000250|UniProtKB:Q8VCX5}.; PTM: Asymmetric dimethylation at Arg-455 by PRMT1 decreases the calcium sensitivity of MICU1 by promoting interaction with UCP2. {ECO:0000269|PubMed:27642082}.; PTM: Degraded by YME1L1 when not complexed as homodimer or heterodimer (PubMed:36206740). Not degraded when complexed as homodimer or heterodimer; the presence of the interchain disulfide bond protecting MICU1 from degradation by YME1L1 (PubMed:36206740). {ECO:0000269|PubMed:36206740}.
uniprot
proteins
protein_family
MICU1 family
uniprot
proteins
protein_family
MICU1 subfamily
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16002733
uniprot
proteins
pubmed
20693986
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21685886
uniprot
proteins
pubmed
22904319
uniprot
proteins
pubmed
23101630
uniprot
proteins
pubmed
23178883
uniprot
proteins
pubmed
23747253
uniprot
proteins
pubmed
24231807
uniprot
proteins
pubmed
24313810
uniprot
proteins
pubmed
24332854
uniprot
proteins
pubmed
24336167
uniprot
proteins
pubmed
24430870
uniprot
proteins
pubmed
24503055
uniprot
proteins
pubmed
24514027
uniprot
proteins
pubmed
24560927
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26341627
uniprot
proteins
pubmed
26387864
uniprot
proteins
pubmed
26489515
uniprot
proteins
pubmed
26903221
uniprot
proteins
pubmed
27099988
uniprot
proteins
pubmed
27123478
uniprot
proteins
pubmed
27642082
uniprot
proteins
pubmed
27818145
uniprot
proteins
pubmed
28615291
uniprot
proteins
pubmed
30082385
uniprot
proteins
pubmed
30403999
uniprot
proteins
pubmed
30454562
uniprot
proteins
pubmed
30638448
uniprot
proteins
pubmed
31397067
uniprot
proteins
pubmed
31427612
uniprot
proteins
pubmed
32148862
uniprot
proteins
pubmed
32395406
uniprot
proteins
pubmed
32494073
uniprot
proteins
pubmed
32667285
uniprot
proteins
pubmed
32762847
uniprot
proteins
pubmed
32790952
uniprot
proteins
pubmed
32862359
uniprot
proteins
pubmed
33428302
uniprot
proteins
pubmed
33969448
uniprot
proteins
pubmed
34463251
uniprot
proteins
pubmed
36206740
uniprot
proteins
pubmed
37036971
uniprot
proteins
pubmed
37098122
uniprot
proteins
pubmed
37126688
uniprot
proteins
pubmed
37244260
uniprot
proteins
pubmed
9806765
uniprot
proteins
sequence_length
476
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion intermembrane space {ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26387864}. Mitochondrion inner membrane {ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24231807, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:27099988, ECO:0000269|PubMed:28615291}. Note=Recruited to the mitochondrial inner membrane by EMRE/SMDT1 (PubMed:30454562). Also localizes to mitochondrial cristae junctions (PubMed:31427612). {ECO:0000269|PubMed:30454562, ECO:0000269|PubMed:31427612}.; SUBCELLULAR LOCATION: [Isoform 6]: Mitochondrion intermembrane space {ECO:0000250|UniProtKB:Q8VCX5}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q8VCX5}.
uniprot
proteins