MCU_MOUSE
ID MCU_MOUSE Reviewed; 350 AA.
AC Q3UMR5; B2RTD1; Q3TTK3;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Calcium uniporter protein, mitochondrial {ECO:0000305};
DE Flags: Precursor;
GN Name=Mcu {ECO:0000312|MGI:MGI:3026965};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-224 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Lung, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=21685886; DOI=10.1038/nature10234;
RA Baughman J.M., Perocchi F., Girgis H.S., Plovanich M., Belcher-Timme C.A.,
RA Sancak Y., Bao X.R., Strittmatter L., Goldberger O., Bogorad R.L.,
RA Koteliansky V., Mootha V.K.;
RT "Integrative genomics identifies MCU as an essential component of the
RT mitochondrial calcium uniporter.";
RL Nature 476:341-345(2011).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=21685888; DOI=10.1038/nature10230;
RA De Stefani D., Raffaello A., Teardo E., Szabo I., Rizzuto R.;
RT "A forty-kilodalton protein of the inner membrane is the mitochondrial
RT calcium uniporter.";
RL Nature 476:336-340(2011).
RN [7]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-251 AND
RP GLU-256, AND TISSUE SPECIFICITY.
RX PubMed=23900286; DOI=10.1038/emboj.2013.157;
RA Raffaello A., De Stefani D., Sabbadin D., Teardo E., Merli G., Picard A.,
RA Checchetto V., Moro S., Szabo I., Rizzuto R.;
RT "The mitochondrial calcium uniporter is a multimer that can include a
RT dominant-negative pore-forming subunit.";
RL EMBO J. 32:2362-2376(2013).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=24212091; DOI=10.1038/ncb2868;
RA Pan X., Liu J., Nguyen T., Liu C., Sun J., Teng Y., Fergusson M.M.,
RA Rovira I.I., Allen M., Springer D.A., Aponte A.M., Gucek M., Balaban R.S.,
RA Murphy E., Finkel T.;
RT "The physiological role of mitochondrial calcium revealed by mice lacking
RT the mitochondrial calcium uniporter.";
RL Nat. Cell Biol. 15:1464-1472(2013).
RN [9]
RP IDENTIFICATION IN A COMPLEX WITH MICU1 AND MICU2, AND TISSUE SPECIFICITY.
RX PubMed=23409044; DOI=10.1371/journal.pone.0055785;
RA Plovanich M., Bogorad R.L., Sancak Y., Kamer K.J., Strittmatter L.,
RA Li A.A., Girgis H.S., Kuchimanchi S., De Groot J., Speciner L., Taneja N.,
RA Oshea J., Koteliansky V., Mootha V.K.;
RT "MICU2, a paralog of MICU1, resides within the mitochondrial uniporter
RT complex to regulate calcium handling.";
RL PLoS ONE 8:E55785-E55785(2013).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-331, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [11]
RP FUNCTION.
RX PubMed=25732818; DOI=10.1016/j.celrep.2015.01.056;
RA Mammucari C., Gherardi G., Zamparo I., Raffaello A., Boncompagni S.,
RA Chemello F., Cagnin S., Braga A., Zanin S., Pallafacchina G., Zentilin L.,
RA Sandri M., De Stefani D., Protasi F., Lanfranchi G., Rizzuto R.;
RT "The mitochondrial calcium uniporter controls skeletal muscle trophism in
RT vivo.";
RL Cell Rep. 10:1269-1279(2015).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26119742; DOI=10.1016/j.celrep.2015.06.002;
RA Kwong J.Q., Lu X., Correll R.N., Schwanekamp J.A., Vagnozzi R.J.,
RA Sargent M.A., York A.J., Zhang J., Bers D.M., Molkentin J.D.;
RT "The mitochondrial calcium uniporter selectively matches metabolic output
RT to acute contractile stress in the heart.";
RL Cell Rep. 12:15-22(2015).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26119731; DOI=10.1016/j.celrep.2015.06.017;
RA Luongo T.S., Lambert J.P., Yuan A., Zhang X., Gross P., Song J.,
RA Shanmughapriya S., Gao E., Jain M., Houser S.R., Koch W.J., Cheung J.Y.,
RA Madesh M., Elrod J.W.;
RT "The mitochondrial calcium uniporter matches energetic supply with cardiac
RT workload during stress and modulates permeability transition.";
RL Cell Rep. 12:23-34(2015).
RN [14]
RP FUNCTION.
RX PubMed=25251370; DOI=10.1111/imm.12392;
RA Bonifaz L., Cervantes-Silva M., Ontiveros-Dotor E., Lopez-Villegas E.,
RA Sanchez-Garcia F.;
RT "A role for mitochondria in antigen processing and presentation.";
RL Immunology 0:0-0(2014).
RN [15]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=26057074; DOI=10.1016/j.yjmcc.2015.05.022;
RA Holmstroem K.M., Pan X., Liu J.C., Menazza S., Liu J., Nguyen T.T., Pan H.,
RA Parks R.J., Anderson S., Noguchi A., Springer D., Murphy E., Finkel T.;
RT "Assessment of cardiac function in mice lacking the mitochondrial calcium
RT uniporter.";
RL J. Mol. Cell. Cardiol. 85:178-182(2015).
RN [16]
RP FUNCTION.
RX PubMed=25603276; DOI=10.1038/ncomms7081;
RA Wu Y., Rasmussen T.P., Koval O.M., Joiner M.L., Hall D.D., Chen B.,
RA Luczak E.D., Wang Q., Rokita A.G., Wehrens X.H., Song L.S., Anderson M.E.;
RT "The mitochondrial uniporter controls fight or flight heart rate
RT increases.";
RL Nat. Commun. 6:6081-6081(2015).
RN [17]
RP FUNCTION.
RX PubMed=26644474; DOI=10.1074/jbc.m115.686956;
RA Marland J.R., Hasel P., Bonnycastle K., Cousin M.A.;
RT "Mitochondrial calcium uptake modulates synaptic vesicle endocytosis in
RT central nerve terminals.";
RL J. Biol. Chem. 291:2080-2086(2016).
CC -!- FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates
CC calcium uptake into mitochondria (PubMed:21685886, PubMed:23900286,
CC PubMed:24212091). Constitutes the pore-forming and calcium-conducting
CC subunit of the uniporter complex (uniplex) (By similarity). Activity is
CC regulated by MICU1 and MICU2 (By similarity). At low Ca(2+) levels MCU
CC activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels
CC MICU1 increases MCU activity (By similarity). Mitochondrial calcium
CC homeostasis plays key roles in cellular physiology and regulates cell
CC bioenergetics, cytoplasmic calcium signals and activation of cell death
CC pathways (By similarity). Involved in buffering the amplitude of
CC systolic calcium rises in cardiomyocytes (By similarity). While
CC dispensable for baseline homeostatic cardiac function, acts as a key
CC regulator of short-term mitochondrial calcium loading underlying a
CC 'fight-or-flight' response during acute stress: acts by mediating a
CC rapid increase of mitochondrial calcium in pacemaker cells
CC (PubMed:26119742, PubMed:26119731, PubMed:25603276). Participates in
CC mitochondrial permeability transition during ischemia-reperfusion
CC injury (PubMed:26119731). Regulates glucose-dependent insulin secretion
CC in pancreatic beta-cells by regulating mitochondrial calcium uptake (By
CC similarity). Mitochondrial calcium uptake in skeletal muscle cells is
CC involved in muscle size in adults (PubMed:25732818). Regulates synaptic
CC vesicle endocytosis kinetics in central nerve terminal
CC (PubMed:26644474). Involved in antigen processing and presentation
CC (PubMed:25251370). {ECO:0000250|UniProtKB:Q8NE86,
CC ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:23900286,
CC ECO:0000269|PubMed:24212091, ECO:0000269|PubMed:25251370,
CC ECO:0000269|PubMed:25603276, ECO:0000269|PubMed:25732818,
CC ECO:0000269|PubMed:26119731, ECO:0000269|PubMed:26119742,
CC ECO:0000269|PubMed:26644474}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative
CC Ru360. {ECO:0000250|UniProtKB:Q8NE86}.
CC -!- SUBUNIT: Component of the uniplex complex, composed of MCU, MCUB,
CC MICU1, MICU2 and EMRE/SMDT1 (By similarity). Heterooligomer with
CC CCDC109B/MCUB; this inhibits channel activity (PubMed:23900286).
CC Homooligomer. Homotetramer (PubMed:23900286). Interacts with MICU1;
CC MICU1 acts as an essential regulator for MCU. Interacts with MCUR1.
CC Interactions with MICU1 and MCUR1 are mutually exclusive. Interacts
CC with MICU2 (By similarity). Interacts with SLC25A23 (By similarity).
CC {ECO:0000250|UniProtKB:Q8NE86, ECO:0000269|PubMed:23409044,
CC ECO:0000269|PubMed:23900286}.
CC -!- INTERACTION:
CC Q3UMR5; Q810S1: Mcub; NbExp=3; IntAct=EBI-776370, EBI-8847756;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:23900286, ECO:0000305|PubMed:26057074}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:23900286}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UMR5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UMR5-2; Sequence=VSP_024264, VSP_024265;
CC -!- TISSUE SPECIFICITY: Detected in heart muscle (at protein level)
CC (PubMed:26057074). Expressed in skeletal muscle, heart, kidney, liver,
CC brain, lung, white fat and spleen. {ECO:0000269|PubMed:21685888,
CC ECO:0000269|PubMed:23409044, ECO:0000269|PubMed:23900286,
CC ECO:0000269|PubMed:26057074}.
CC -!- DOMAIN: The N-terminal domain is required for efficient Ca(2+) uptake
CC and for interaction with MCUR1. It is not required for targeting to the
CC mitochondria, oligomerization, interaction with MICU1 and MICU2, or
CC assembly of the uniplex complex. {ECO:0000250|UniProtKB:Q8NE86}.
CC -!- DOMAIN: Forms a well-packed pentamer with an overall cylindrical shape.
CC The inner core of the pentamer is formed with the second transmembrane
CC region and the second coiled-coil region: while the transmembrane
CC regions pack into a five-helix bundle having a largely polar pore
CC across the membrane, the coiled-coil outside the membrane forms a
CC pentamer with a hydrophobic core. The inner core is wrapped by the
CC first transmembrane region through contacts between the first and the
CC second transmembrane regions. The second transmembrane is followed by
CC the inner juxtamembrane region (IJMH) that orients at a wide angle
CC relative to the second transmembrane. The two core domains are held
CC together on the periphery by the outer juxtamembrane helix (OJMH).
CC {ECO:0000250|UniProtKB:Q21121}.
CC -!- DOMAIN: The critical DXXE motif connecting the transmembrane regions
CC forms a pentameric barrel that constitutes the mouth of the pore.
CC Inside the barrel, two acidic residues are in position to form two
CC carboxylate rings. In absence of SMDT1/EMRE regulator, the calcium ions
CC cannot exit the channel, suggesting that SMDT1/EMRE-binding induces
CC conformational rearrangements to allow calcium to exit.
CC {ECO:0000250|UniProtKB:Q21121}.
CC -!- PTM: Phosphorylation by CaMK2 in heart leads to increased MCU current.
CC The regulation of MCU by CaMK2 is however subject to discussion:
CC another group was unable to reproduce these results. Phosphorylated on
CC tyrosines by PTK2B/PYK2, promoting oligomerization.
CC {ECO:0000250|UniProtKB:Q8NE86}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:24212091,
CC PubMed:26057074). Although slightly smaller, mice are grossly normal.
CC Only minor alterations in basal energetics are observed. Cells show a
CC strong reduction, but not a complete absence, of mitochondrial matrix
CC calcium. The skeletal muscles exhibit alterations in the
CC phosphorylation and activity of pyruvate dehydrogenase and mice show
CC defects in ability to perform strenuous work. Mitochondria lack
CC evidence for calcium-induced permeability transition pore (PTP) opening
CC (PubMed:24212091). Mitochondria from mutant mouse heart muscle have
CC impaired Ca(2+) uptake and reduced Ca(2+) levels in the mitochondrial
CC matrix; still, mutant mice have apparently normal heart function and
CC display no cardiac defects (PubMed:26057074). Conditional mutant mice
CC with cardiomyocyte-specific deletion of Mcu in adults display no overt
CC baseline phenotype and are protected against mitochondrial calcium
CC overload by preventing the activation of the mitochondrial permeability
CC transition pore (PubMed:26119742, PubMed:26119731). Mice however lack
CC contractile responsiveness to acute stress and 'fight-or-flight'
CC response: they produce mitochondria refractory to acute calcium uptake,
CC with impaired ATP production and inhibited mitochondrial permeability
CC transition pore opening upon acute calcium challenge (PubMed:26119742,
CC PubMed:26119731). {ECO:0000269|PubMed:24212091,
CC ECO:0000269|PubMed:26057074, ECO:0000269|PubMed:26119731,
CC ECO:0000269|PubMed:26119742}.
CC -!- SIMILARITY: Belongs to the MCU (TC 1.A.77) family. {ECO:0000305}.
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DR EMBL; AK144727; BAE26033.1; -; mRNA.
DR EMBL; AK161322; BAE36322.1; -; mRNA.
DR EMBL; AC155940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022699; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC139254; AAI39255.1; -; mRNA.
DR EMBL; BC139257; AAI39258.1; -; mRNA.
DR CCDS; CCDS23866.2; -. [Q3UMR5-1]
DR RefSeq; NP_001028431.2; NM_001033259.4. [Q3UMR5-1]
DR AlphaFoldDB; Q3UMR5; -.
DR SMR; Q3UMR5; -.
DR BioGRID; 229684; 7.
DR IntAct; Q3UMR5; 3.
DR MINT; Q3UMR5; -.
DR STRING; 10090.ENSMUSP00000020312; -.
DR TCDB; 1.A.77.1.1; the mg(2+)/ca(2+) uniporter (mcu) family.
DR iPTMnet; Q3UMR5; -.
DR PhosphoSitePlus; Q3UMR5; -.
DR SwissPalm; Q3UMR5; -.
DR EPD; Q3UMR5; -.
DR jPOST; Q3UMR5; -.
DR MaxQB; Q3UMR5; -.
DR PaxDb; Q3UMR5; -.
DR PeptideAtlas; Q3UMR5; -.
DR PRIDE; Q3UMR5; -.
DR ProteomicsDB; 252754; -. [Q3UMR5-1]
DR ProteomicsDB; 252755; -. [Q3UMR5-2]
DR Antibodypedia; 3091; 85 antibodies from 21 providers.
DR Ensembl; ENSMUST00000009791; ENSMUSP00000009791; ENSMUSG00000009647. [Q3UMR5-2]
DR Ensembl; ENSMUST00000020312; ENSMUSP00000020312; ENSMUSG00000009647. [Q3UMR5-1]
DR GeneID; 215999; -.
DR KEGG; mmu:215999; -.
DR UCSC; uc007fds.3; mouse. [Q3UMR5-2]
DR UCSC; uc007fdt.3; mouse. [Q3UMR5-1]
DR CTD; 90550; -.
DR MGI; MGI:3026965; Mcu.
DR VEuPathDB; HostDB:ENSMUSG00000009647; -.
DR eggNOG; KOG2966; Eukaryota.
DR GeneTree; ENSGT00940000157528; -.
DR HOGENOM; CLU_056554_0_0_1; -.
DR InParanoid; Q3UMR5; -.
DR OMA; DDIYVEY; -.
DR OrthoDB; 1076768at2759; -.
DR PhylomeDB; Q3UMR5; -.
DR TreeFam; TF314435; -.
DR Reactome; R-MMU-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 215999; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Mcu; mouse.
DR PRO; PR:Q3UMR5; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3UMR5; protein.
DR Bgee; ENSMUSG00000009647; Expressed in animal zygote and 235 other tissues.
DR ExpressionAtlas; Q3UMR5; baseline and differential.
DR Genevisible; Q3UMR5; MM.
DR GO; GO:0034704; C:calcium channel complex; IDA:UniProtKB.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:1990246; C:uniplex complex; IDA:MGI.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015292; F:uniporter activity; ISS:UniProtKB.
DR GO; GO:0090527; P:actin filament reorganization; ISO:MGI.
DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISO:MGI.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISO:MGI.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR InterPro; IPR006769; MCU_C.
DR InterPro; IPR039055; MCU_fam.
DR PANTHER; PTHR13462; PTHR13462; 1.
DR Pfam; PF04678; MCU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Coiled coil; Ion channel; Ion transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phosphoprotein;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix;
KW Transport.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 50..350
FT /note="Calcium uniporter protein, mitochondrial"
FT /id="PRO_0000282977"
FT TOPO_DOM 50..232
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 233..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..264
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 265..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..350
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT REGION 74..164
FT /note="N-terminal MCU domain"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT REGION 215..233
FT /note="Outer juxtamembrane helix (OJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT REGION 282..291
FT /note="Inner juxtamembrane helix (IJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT COILED 191..220
FT /evidence="ECO:0000255"
FT COILED 310..338
FT /evidence="ECO:0000255"
FT MOTIF 260..263
FT /note="DXXE"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT MOD_RES 56
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT MOD_RES 91
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT MOD_RES 331
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT VAR_SEQ 1..149
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_024264"
FT VAR_SEQ 150..164
FT /note="LVINDLTYHVRPPKR -> MILRPKQLFSAFTKQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_024265"
FT MUTAGEN 251
FT /note="R->W: Strongly reduces calcium channel activity;
FT when associated with V-256."
FT /evidence="ECO:0000269|PubMed:23900286"
FT MUTAGEN 256
FT /note="E->V: Strongly reduces calcium channel activity;
FT when associated with W-251."
FT /evidence="ECO:0000269|PubMed:23900286"
SQ SEQUENCE 350 AA; 39682 MW; FB3089AADF7FB2E3 CRC64;
MAAAAGRSLL LLLCSRGGGG GAGGCGALTA GCFPGLGVSR HRPHQQHRTA HQRPASWQSV
GAAYCSTVVP SDDVTVVYQN GLPVISVRLP SRRERCQFTL KPISDSVGVF LRQLQEEDRG
IDRVAIYSPD GVRVAASTGI DLLLLDDFKL VINDLTYHVR PPKRDLLSHE DAATLNDVKT
LVQQLYTTLC IEQHQLNKER ELVERLEDLK QQLAPLEKVR IEISRKAEKR TTLVLWGGLA
YMATQFGILA RLTWWEYSWD IMEPVTYFIT YGSAMAMYAY FVMTRQEYVY PEARDRQYLL
FFHKGAKKSR FDLEKYNQLK DAIAQAEMDL KRLRDPLQVH LPLRQIGEKE
