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Aliases for MCU Gene

Aliases for MCU Gene

  • Mitochondrial Calcium Uniporter 2 3 5
  • Coiled-Coil Domain-Containing Protein 109A 3 4
  • C10orf42 3 4
  • CCDC109A 3 4
  • HsMCU 3 4
  • Calcium Uniporter Protein, Mitochondrial 3
  • Coiled-Coil Domain Containing 109A 2

External Ids for MCU Gene

Previous HGNC Symbols for MCU Gene

  • C10orf42
  • CCDC109A

Previous GeneCards Identifiers for MCU Gene

  • GC10P074452

Summaries for MCU Gene

Entrez Gene Summary for MCU Gene

  • This gene encodes a calcium transporter that localizes to the mitochondrial inner membrane. The encoded protein interacts with mitochondrial calcium uptake 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

GeneCards Summary for MCU Gene

MCU (Mitochondrial Calcium Uniporter) is a Protein Coding gene. Diseases associated with MCU include Ischemia and Urethral Calculus. Among its related pathways are Calcium signaling pathway and Toll-like receptor signaling pathway. Gene Ontology (GO) annotations related to this gene include identical protein binding and uniporter activity. An important paralog of this gene is MCUB.

UniProtKB/Swiss-Prot for MCU Gene

  • Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:21685888, PubMed:21685886, PubMed:23101630, PubMed:22904319, PubMed:23178883, PubMed:22829870, PubMed:22822213, PubMed:24332854, PubMed:23755363, PubMed:26341627). Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex) (PubMed:23755363). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity (PubMed:24560927, PubMed:26903221). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213). 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). participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319, PubMed:22829870). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Involved in antigen processing and presentation (By similarity).

Additional gene information for MCU Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MCU Gene

Genomics for MCU Gene

GeneHancer (GH) Regulatory Elements for MCU Gene

Promoters and enhancers for MCU Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH10I072689 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE 552.7 -0.5 -524 4.8 HDGF PKNOX1 SMAD1 FOXA2 ARID4B SIN3A YBX1 YY1 SLC30A9 ZNF143 MCU DNAJB12 ENSG00000272791 ECD ENSG00000268584 DNAJC9 MICU1 ENSG00000227540 ENSG00000272630 CHST3
GH10I072522 Promoter/Enhancer 1.4 EPDnew ENCODE 11.1 -167.6 -167644 4 FOXA2 INSM2 MZF1 FEZF1 RARA YY1 ZSCAN5C ZNF391 CREM MIXL1 MICU1 DNAJB12 ENSG00000226163 MCU CFAP70 ENSG00000230609
GH10I072735 Enhancer 1 Ensembl ENCODE 11.9 +46.3 46259 6 PKNOX1 FOXA2 JUN ZIC2 ZNF2 RARA FOSL1 ZSCAN5C PRDM10 FOSL2 MCU DNAJB12 RNU6-805P ENSG00000226163 ENSG00000280166 ENSG00000279502
GH10I072567 Enhancer 1.1 FANTOM5 Ensembl ENCODE 10.8 -124.5 -124519 1.2 CTCF TRIM22 MAFG REST RAD21 MAFF ZNF316 JUND ZNF143 CREB1 DNAJB12 MCU DDIT4 ENSG00000230609 RN7SL840P MICU1
GH10I072562 Enhancer 1.1 FANTOM5 Ensembl ENCODE 10.6 -128.2 -128238 2.6 CBFB MAX JUNB ELF1 DPF2 BATF ATF2 IKZF1 ATF7 ETV6 DNAJB12 MCU CFAP70 DDIT4 ENSG00000230609 RN7SL840P MICU1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MCU on UCSC Golden Path with GeneCards custom track

Genomic Locations for MCU Gene

Genomic Locations for MCU Gene
chr10:72,692,131-72,887,694
(GRCh38/hg38)
Size:
195,564 bases
Orientation:
Plus strand
chr10:74,451,889-74,647,452
(GRCh37/hg19)

Genomic View for MCU Gene

Genes around MCU on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MCU Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MCU Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MCU Gene

Proteins for MCU Gene

  • Protein details for MCU Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NE86-MCU_HUMAN
    Recommended name:
    Calcium uniporter protein, mitochondrial
    Protein Accession:
    Q8NE86
    Secondary Accessions:
    • B2RDF3
    • B3KXV7
    • Q96FL3

    Protein attributes for MCU Gene

    Size:
    351 amino acids
    Molecular mass:
    39867 Da
    Quaternary structure:
    • Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807). Homooligomer (PubMed:21685886, PubMed:26341627). Forms a pentamer (By similarity). Heterooligomer with CCDC109B/MCUB; this inhibits channel activity (By similarity). Interacts with MICU1; MICU1 acts as an essential regulator for MCU (PubMed:21685886, PubMed:23101630, PubMed:23178883, PubMed:24332854, PubMed:26341627). Interacts with MCUR1 (PubMed:23178883, PubMed:26341627, PubMed:27184846, PubMed:26976564). Interacts with CCDC90B (PubMed:27184846). Interactions with MICU1 and MCUR1 are mutually exclusive (PubMed:23178883). Interacts with MICU2 (PubMed:26341627). Interacts with SLC25A23 (PubMed:24430870).

    Three dimensional structures from OCA and Proteopedia for MCU Gene

    Alternative splice isoforms for MCU Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MCU Gene

Post-translational modifications for MCU Gene

  • Phosphorylation by CaMK2 in heart leads to increased MCU current (PubMed:23051746, PubMed:25254481). The regulation of MCU by CaMK2 is however subject to discussion: another group was unable to reproduce these results (PubMed:25254480). Phosphorylated on tyrosines by PTK2B/PYK2, promoting oligomerization (PubMed:24800979).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MCU Gene

Domains & Families for MCU Gene

Gene Families for MCU Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for MCU Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MCU Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8NE86

UniProtKB/Swiss-Prot:

MCU_HUMAN :
  • The N-terminal MCU domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex.
  • Belongs to the MCU (TC 1.A.77) family.
Domain:
  • The N-terminal MCU domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex.
  • Forms a well-packed pentamer with an overall cylindrical shape. The inner core of the pentamer is formed with the second transmembrane region and the second coiled-coil region: while the transmembrane regions pack into a five-helix bundle having a largely polar pore across the membrane, the coiled-coil outside the membrane forms a pentamer with a hydrophobic core. The inner core is wrapped by the first transmembrane region through contacts between the first and the second transmembrane regions. The second transmembrane is followed by the inner juxtamembrane region (IJMH) that orients at a wide angle relative to the second transmembrane. The two core domains are held together on the periphery by the outer juxtamembrane helix (OJMH).
  • The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, two acidic residues are in position to form two carboxylate rings. In absence of SMDT1/EMRE regulator, the calcium ions cannot exit the channel, suggesting that SMDT1/EMRE-binding induces conformational rearrangements to allow calcium to exit.
Family:
  • Belongs to the MCU (TC 1.A.77) family.
genes like me logo Genes that share domains with MCU: view

Function for MCU Gene

Molecular function for MCU Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by ruthenium red or its derivative Ru360.
UniProtKB/Swiss-Prot Function:
Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:21685888, PubMed:21685886, PubMed:23101630, PubMed:22904319, PubMed:23178883, PubMed:22829870, PubMed:22822213, PubMed:24332854, PubMed:23755363, PubMed:26341627). Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex) (PubMed:23755363). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity (PubMed:24560927, PubMed:26903221). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (PubMed:22822213). 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). participates in mitochondrial permeability transition during ischemia-reperfusion injury (By similarity). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319, PubMed:22829870). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (By similarity). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (By similarity). Involved in antigen processing and presentation (By similarity).
UniProtKB/Swiss-Prot Induction:
MCU transcripts are down-regulated by microRNA miR-25 (PubMed:23246404). Down-regulation by miR-25 may protect cardiomyocytes against oxidative damage in cardiomyocytes (PubMed:25764156).

Gene Ontology (GO) - Molecular Function for MCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005262 calcium channel activity IMP 23755363
GO:0005515 protein binding IPI 21685886
GO:0015292 uniporter activity IMP 23755363
GO:0042802 identical protein binding IEA --
genes like me logo Genes that share ontologies with MCU: view
genes like me logo Genes that share phenotypes with MCU: view

Animal Models for MCU Gene

MGI Knock Outs for MCU:
  • Mcu tm1b(EUCOMM)Hmgu

Clone Products

  • Addgene plasmids for MCU

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MCU Gene

Localization for MCU Gene

Subcellular locations from UniProtKB/Swiss-Prot for MCU Gene

Mitochondrion inner membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MCU gene
Compartment Confidence
mitochondrion 5
plasma membrane 2
endoplasmic reticulum 2
cytosol 2
extracellular 1
peroxisome 1
nucleus 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA,IDA --
GO:0005743 mitochondrial inner membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0031305 integral component of mitochondrial inner membrane IDA 23755363
genes like me logo Genes that share ontologies with MCU: view

Pathways & Interactions for MCU Gene

genes like me logo Genes that share pathways with MCU: view

Pathways by source for MCU Gene

1 Cell Signaling Technology pathway for MCU Gene

Gene Ontology (GO) - Biological Process for MCU Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0006811 ion transport IEA --
GO:0006816 calcium ion transport IEA --
GO:0006851 mitochondrial calcium ion transmembrane transport IMP,TAS --
GO:0019722 calcium-mediated signaling IDA 21685886
genes like me logo Genes that share ontologies with MCU: view

No data available for SIGNOR curated interactions for MCU Gene

Drugs & Compounds for MCU Gene

No Compound Related Data Available

Transcripts for MCU Gene

Unigene Clusters for MCU Gene

Mitochondrial calcium uniporter:
Representative Sequences:

Clone Products

  • Addgene plasmids for MCU

Alternative Splicing Database (ASD) splice patterns (SP) for MCU Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b · 11c ^ 12 ^ 13a · 13b ^ 14
SP1: - - - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - - - - -
SP4: - -
SP5:
SP6: - -
SP7: - -

Relevant External Links for MCU Gene

GeneLoc Exon Structure for
MCU
ECgene alternative splicing isoforms for
MCU

Expression for MCU Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MCU Gene

mRNA differential expression in normal tissues according to GTEx for MCU Gene

This gene is overexpressed in Muscle - Skeletal (x4.4).

Protein differential expression in normal tissues from HIPED for MCU Gene

This gene is overexpressed in Nasal epithelium (53.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MCU Gene



Protein tissue co-expression partners for MCU Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MCU Gene:

MCU

SOURCE GeneReport for Unigene cluster for MCU Gene:

Hs.591366

Evidence on tissue expression from TISSUES for MCU Gene

  • Eye(4.1)
  • Nervous system(3.2)
  • Muscle(2.7)
  • Heart(2.6)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with MCU: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MCU Gene

Orthologs for MCU Gene

This gene was present in the common ancestor of animals.

Orthologs for MCU Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MCU 33 34
  • 99.34 (n)
cow
(Bos Taurus)
Mammalia MCU 33 34
  • 95.25 (n)
dog
(Canis familiaris)
Mammalia MCU 33 34
  • 94.88 (n)
oppossum
(Monodelphis domestica)
Mammalia MCU 34
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mcu 33
  • 88.4 (n)
mouse
(Mus musculus)
Mammalia Mcu 33 16 34
  • 88.19 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MCU 34
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves MCU 33 34
  • 81.7 (n)
lizard
(Anolis carolinensis)
Reptilia MCU 34
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mcu 33
  • 75.98 (n)
zebrafish
(Danio rerio)
Actinopterygii mcu 33 34
  • 70.72 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP006330 33
  • 54.33 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG18769 33 34
  • 50.7 (n)
worm
(Caenorhabditis elegans)
Secernentea mcu-1 33 34
  • 49.94 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 55 (a)
OneToMany
Species where no ortholog for MCU was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MCU Gene

ENSEMBL:
Gene Tree for MCU (if available)
TreeFam:
Gene Tree for MCU (if available)

Paralogs for MCU Gene

Paralogs for MCU Gene

(1) SIMAP similar genes for MCU Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with MCU: view

Variants for MCU Gene

Sequence variations from dbSNP and Humsavar for MCU Gene

SNP ID Clin Chr 10 pos Variation AA Info Type
rs1000002936 -- 72,825,026(+) G/A intron_variant
rs1000031837 -- 72,823,054(+) C/T intron_variant
rs1000047285 -- 72,734,011(+) T/C intron_variant
rs1000082840 -- 72,779,052(+) C/G intron_variant
rs1000083818 -- 72,885,888(+) A/T 3_prime_UTR_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for MCU Gene

Variant ID Type Subtype PubMed ID
esv2759767 CNV gain 17122850
esv3623805 CNV loss 21293372
nsv1144502 CNV deletion 24896259
nsv7121 CNV insertion 18451855

Variation tolerance for MCU Gene

Residual Variation Intolerance Score: 40.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.35; 26.79% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MCU Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MCU

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MCU Gene

Disorders for MCU Gene

MalaCards: The human disease database

(9) MalaCards diseases for MCU Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
ischemia
  • acute coronary syndrome
urethral calculus
  • urethral stone
acute cystitis
  • urinary tract infection
urethral diverticulum
bladder disease
  • urinary bladder disease
- elite association - COSMIC cancer census association via MalaCards
Search MCU in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with MCU: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MCU Gene

Publications for MCU Gene

  1. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. (PMID: 21685886) Baughman JM … Mootha VK (Nature 2011) 2 3 4 58
  2. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. (PMID: 21685888) De Stefani D … Rizzuto R (Nature 2011) 2 3 4 58
  3. Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex. (PMID: 27099988) Tsai MF … Miller C (eLife 2016) 3 4 58
  4. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics. (PMID: 27184846) Tomar D … Madesh M (Cell reports 2016) 3 4 58
  5. Structure and function of the N-terminal domain of the human mitochondrial calcium uniporter. (PMID: 26341627) Lee Y … Eom SH (EMBO reports 2015) 3 4 58

Products for MCU Gene

  • Addgene plasmids for MCU

Sources for MCU Gene

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