Mcu
entrez
215999
canonical
uniprot
Q3UMR5
canonical
ensembl
ENSMUSG00000009647
resolver
ensp
ENSMUSP00000020312
resolver
genesymbol
Mcu
resolver
uniprot
B2RTD1
resolver
uniprot
Q3TTK3
resolver
uniprot_entry
MCU_MOUSE
resolver
uniprot_sec
B2RTD1
resolver
uniprot_sec
Q3TTK3
resolver
activity_regulation
ACTIVITY REGULATION: MCU channel activity is regulated by the heterodimer composed of MICU1 and either MICU2 or MICU3, which act as calcium-sensors (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 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 channel (By similarity). MCU channel activity is gated by EMRE/SMDT1 via the juxtamembrane helix loop (By similarity). Inhibited by ruthenium red or its derivative Ru360 (By similarity). {ECO:0000250|UniProtKB:Q8NE86}.
uniprot
proteins
amino_acid_sequence
MAAAAGRSLLLLLCSRGGGGGAGGCGALTAGCFPGLGVSRHRPHQQHRTAHQRPASWQSVGAAYCSTVVPSDDVTVVYQNGLPVISVRLPSRRERCQFTLKPISDSVGVFLRQLQEEDRGIDRVAIYSPDGVRVAASTGIDLLLLDDFKLVINDLTYHVRPPKRDLLSHEDAATLNDVKTLVQQLYTTLCIEQHQLNKERELVERLEDLKQQLAPLEKVRIEISRKAEKRTTLVLWGGLAYMATQFGILARLTWWEYSWDIMEPVTYFITYGSAMAMYAYFVMTRQEYVYPEARDRQYLLFFHKGAKKSRFDLEKYNQLKDAIAQAEMDLKRLRDPLQVHLPLRQIGEKE
uniprot
proteins
function
FUNCTION: Channel-forming and calcium-conducting subunit of the mitochondrial inner membrane calcium uniporter complex (uniplex), which mediates calcium uptake into the mitochondrial matrix (PubMed:21685886, PubMed:23900286, PubMed:24212091). MCU channel activity is regulated by the calcium-sensor subunits of the uniplex MICU1 and MICU2 (or MICU3) (By similarity). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates ATP production, cytoplasmic calcium signals and activation of cell death pathways (By similarity). Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (By similarity). While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:25603276, PubMed:26119731, PubMed:26119742). Participates in mitochondrial permeability transition during ischemia-reperfusion injury (PubMed:26119731). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (PubMed:25732818). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (PubMed:26644474). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Involved in antigen processing and presentation (PubMed:25251370). {ECO:0000250|UniProtKB:Q8NE86, ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:23900286, ECO:0000269|PubMed:24212091, ECO:0000269|PubMed:25251370, ECO:0000269|PubMed:25603276, ECO:0000269|PubMed:25732818, ECO:0000269|PubMed:26119731, ECO:0000269|PubMed:26119742, ECO:0000269|PubMed:26644474}.
uniprot
proteins
mass_dalton
39682
uniprot
proteins
mutagenesis
MUTAGEN 251; /note="R->W: Strongly reduces calcium channel activity; when associated with V-256."; /evidence="ECO:0000269|PubMed:23900286"; MUTAGEN 256; /note="E->V: Strongly reduces calcium channel activity; when associated with W-251."; /evidence="ECO:0000269|PubMed:23900286
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by CaMK2 in heart leads to increased MCU current. The regulation of MCU by CaMK2 is however subject to discussion: another group was unable to reproduce these results. Phosphorylated on tyrosines by PTK2B/PYK2, promoting oligomerization. {ECO:0000250|UniProtKB:Q8NE86}.; PTM: Glutathionylation at Cys-96 in response to reactive oxygen species (ROS) promotes MCU higher-order assembly, leading to constitutive activation of the MCU channel and mitochondrial calcium overload. {ECO:0000250|UniProtKB:Q8NE86}.; PTM: Undergoes proteolytic degradation by SPG7. {ECO:0000250|UniProtKB:Q8NE86}.
uniprot
proteins
protein_family
MCU (TC 1.A.77) family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21685886
uniprot
proteins
pubmed
21685888
uniprot
proteins
pubmed
23409044
uniprot
proteins
pubmed
23576753
uniprot
proteins
pubmed
23900286
uniprot
proteins
pubmed
24212091
uniprot
proteins
pubmed
25251370
uniprot
proteins
pubmed
25603276
uniprot
proteins
pubmed
25732818
uniprot
proteins
pubmed
26057074
uniprot
proteins
pubmed
26119731
uniprot
proteins
pubmed
26119742
uniprot
proteins
pubmed
26644474
uniprot
proteins
sequence_length
350
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000269|PubMed:23900286, ECO:0000305|PubMed:26057074}; Multi-pass membrane protein {ECO:0000269|PubMed:23900286}.
uniprot
proteins
transmembrane_region
TRANSMEM 233..256; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 265..282; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins