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Q8NE86 (MCU_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium uniporter protein, mitochondrial
Alternative name(s):
Coiled-coil domain-containing protein 109A
Gene names
Name:MCU
Synonyms:C10orf42, CCDC109A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Activity is regulated by MICU1 and MICU2 that stimulate and inhibit MCU activity, respectively. Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake. Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16

Subunit structure

Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1. Heterotetramer with CCDC109B/MCUB; this inhibits channel activity By similarity. Homotetramer. Interacts with MICU1; MICU1 acts as an essential regulator for MCU. Interacts with MCUR1; interaction with MICU1 and MCUR1 are mutually exclusive. Ref.7 Ref.8 Ref.10 Ref.14 Ref.15

Subcellular location

Mitochondrion inner membrane; Multi-pass membrane protein Ref.6 Ref.7 Ref.15.

Sequence similarities

Belongs to the MCU family.

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentMembrane
Mitochondrion
Mitochondrion inner membrane
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Ion channel
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium-mediated signaling

Inferred from direct assay Ref.7Ref.6. Source: UniProtKB

glucose homeostasis

Inferred from mutant phenotype Ref.11. Source: UniProtKB

mitochondrial calcium ion transport

Inferred from direct assay Ref.6Ref.16. Source: UniProtKB

positive regulation of insulin secretion

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of mitochondrial calcium ion concentration

Inferred from direct assay Ref.6Ref.16. Source: UniProtKB

protein complex oligomerization

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentcalcium channel complex

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of mitochondrial inner membrane

Inferred from direct assay Ref.15. Source: UniProtKB

mitochondrial inner membrane

Inferred from direct assay Ref.7Ref.6. Source: UniProtKB

uniplex complex

Inferred from direct assay Ref.15Ref.16. Source: UniProtKB

   Molecular_functioncalcium channel activity

Inferred from direct assay Ref.6Ref.16. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7Ref.8Ref.10. Source: UniProtKB

uniporter activity

Inferred from direct assay Ref.7Ref.6Ref.16. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8NE86-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8NE86-2)

The sequence of this isoform differs from the canonical sequence as follows:
     166-219: DLLSHENAAT...LKEQLAPLEK → VEMGFCHVGQNGFELLTSSYLPASASQSAEIIA
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8NE86-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: MAAAAGRSLLLLLSSRGGGGGGAGGCGALTAGCFPGLGVSRHRQQQHHRT → M

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 351351Calcium uniporter protein, mitochondrial
PRO_0000282976

Regions

Topological domain1 – 233233Mitochondrial matrix Potential
Transmembrane234 – 25623Helical; Potential
Topological domain257 – 2659Mitochondrial intermembrane Potential
Transmembrane266 – 28318Helical; Potential
Topological domain284 – 35168Mitochondrial matrix Potential
Coiled coil192 – 22332 Potential
Coiled coil311 – 33929 Potential

Amino acid modifications

Modified residue3321N6-acetyllysine By similarity

Natural variations

Alternative sequence1 – 5050MAAAA…QHHRT → M in isoform 3.
VSP_041687
Alternative sequence166 – 21954DLLSH…APLEK → VEMGFCHVGQNGFELLTSSY LPASASQSAEIIA in isoform 2.
VSP_024263

Experimental info

Mutagenesis2571E → A: Inhibits calcium uptake. Ref.7
Mutagenesis2591S → A: Does not inhibit calcium uptake. Ref.7
Mutagenesis2611D → A: Inhibits calcium uptake. Inhibits calcium channel activity; when associated with Q-264. Ref.6 Ref.7
Mutagenesis2641E → A: Inhibits calcium uptake. Inhibits calcium channel activity; when associated with Q-261. Ref.6 Ref.7
Sequence conflict1071S → P in BAG37900. Ref.1
Sequence conflict1421D → Y in BAG37900. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 50205D01055D66E4

FASTA35139,867
        10         20         30         40         50         60 
MAAAAGRSLL LLLSSRGGGG GGAGGCGALT AGCFPGLGVS RHRQQQHHRT VHQRIASWQN 

        70         80         90        100        110        120 
LGAVYCSTVV PSDDVTVVYQ NGLPVISVRL PSRRERCQFT LKPISDSVGV FLRQLQEEDR 

       130        140        150        160        170        180 
GIDRVAIYSP DGVRVAASTG IDLLLLDDFK LVINDLTYHV RPPKRDLLSH ENAATLNDVK 

       190        200        210        220        230        240 
TLVQQLYTTL CIEQHQLNKE RELIERLEDL KEQLAPLEKV RIEISRKAEK RTTLVLWGGL 

       250        260        270        280        290        300 
AYMATQFGIL ARLTWWEYSW DIMEPVTYFI TYGSAMAMYA YFVMTRQEYV YPEARDRQYL 

       310        320        330        340        350 
LFFHKGAKKS RFDLEKYNQL KDAIAQAEMD LKRLRDPLQV HLPLRQIGEK D 

« Hide

Isoform 2 [UniParc].

Checksum: 56D458541240604A
Show »

FASTA33036,996
Isoform 3 [UniParc].

Checksum: 65C6D99CD9D2D3FC
Show »

FASTA30235,159

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
Tissue: Testis and Tongue.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Eye and Testis.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter."
De Stefani D., Raffaello A., Teardo E., Szabo I., Rizzuto R.
Nature 476:336-340(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-261 AND GLU-264, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter."
Baughman J.M., Perocchi F., Girgis H.S., Plovanich M., Belcher-Timme C.A., Sancak Y., Bao X.R., Strittmatter L., Goldberger O., Bogorad R.L., Koteliansky V., Mootha V.K.
Nature 476:341-345(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, OLIGOMERIZATION, INTERACTION WITH MICU1, MUTAGENESIS OF GLU-257; SER-259; ASP-261 AND GLU-264, SUBCELLULAR LOCATION.
[8]"MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival."
Mallilankaraman K., Doonan P., Cardenas C., Chandramoorthy H.C., Muller M., Miller R., Hoffman N.E., Gandhirajan R.K., Molgo J., Birnbaum M.J., Rothberg B.S., Mak D.O., Foskett J.K., Madesh M.
Cell 151:630-644(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MICU1.
[9]"Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) contribute to metabolism-secretion coupling in clonal pancreatic beta-cells."
Alam M.R., Groschner L.N., Parichatikanond W., Kuo L., Bondarenko A.I., Rost R., Waldeck-Weiermair M., Malli R., Graier W.F.
J. Biol. Chem. 287:34445-34454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"MCUR1 is an essential component of mitochondrial Ca(2+) uptake that regulates cellular metabolism."
Mallilankaraman K., Cardenas C., Doonan P.J., Chandramoorthy H.C., Irrinki K.M., Golenar T., Csordas G., Madireddi P., Yang J., Muller M., Miller R., Kolesar J.E., Molgo J., Kaufman B., Hajnoczky G., Foskett J.K., Madesh M.
Nat. Cell Biol. 14:1336-1343(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MCUR1 AND MICU1.
[11]"The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic beta-cells."
Tarasov A.I., Semplici F., Ravier M.A., Bellomo E.A., Pullen T.J., Gilon P., Sekler I., Rizzuto R., Rutter G.A.
PLoS ONE 7:E39722-E39722(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Mitochondrial Ca2+ uptake contributes to buffering cytoplasmic Ca2+ peaks in cardiomyocytes."
Drago I., De Stefani D., Rizzuto R., Pozzan T.
Proc. Natl. Acad. Sci. U.S.A. 109:12986-12991(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Evolutionary diversity of the mitochondrial calcium uniporter."
Bick A.G., Calvo S.E., Mootha V.K.
Science 336:886-886(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[14]"MICU1 motifs define mitochondrial calcium uniporter binding and activity."
Hoffman N.E., Chandramoorthy H.C., Shamugapriya S., Zhang X., Rajan S., Mallilankaraman K., Gandhirajan R.K., Vagnozzi R.J., Ferrer L.M., Sreekrishnanilayam K., Natarajaseenivasan K., Vallem S., Force T., Choi E.T., Cheung J.Y., Madesh M.
Cell Rep. 5:1576-1588(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MICU1.
[15]"EMRE is an essential component of the mitochondrial calcium uniporter complex."
Sancak Y., Markhard A.L., Kitami T., Kovacs-Bogdan E., Kamer K.J., Udeshi N.D., Carr S.A., Chaudhuri D., Clapham D.E., Li A.A., Calvo S.E., Goldberger O., Mootha V.K.
Science 342:1379-1382(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, IDENTIFICATION IN THE UNIPLEX COMPLEX.
[16]"MICU1 and MICU2 finely tune the mitochondrial Ca(2+) uniporter by exerting opposite effects on MCU activity."
Patron M., Checchetto V., Raffaello A., Teardo E., Vecellio Reane D., Mantoan M., Granatiero V., Szabo I., De Stefani D., Rizzuto R.
Mol. Cell 53:726-737(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK315519 mRNA. Translation: BAG37900.1.
AK128016 mRNA. Translation: BAG54619.1.
AC016542 Genomic DNA. No translation available.
AC069548 Genomic DNA. No translation available.
CH471083 Genomic DNA. Translation: EAW54461.1.
BC010682 mRNA. Translation: AAH10682.1.
BC034235 mRNA. Translation: AAH34235.1.
CCDSCCDS59218.1. [Q8NE86-2]
CCDS59219.1. [Q8NE86-3]
CCDS7317.1. [Q8NE86-1]
RefSeqNP_001257608.1. NM_001270679.1. [Q8NE86-2]
NP_001257609.1. NM_001270680.1. [Q8NE86-3]
NP_612366.1. NM_138357.2. [Q8NE86-1]
UniGeneHs.591366.

3D structure databases

ProteinModelPortalQ8NE86.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124733. 7 interactions.
DIPDIP-60468N.
IntActQ8NE86. 2 interactions.
MINTMINT-8051705.
STRING9606.ENSP00000362144.

PTM databases

PhosphoSiteQ8NE86.

Polymorphism databases

DMDM74730222.

Proteomic databases

MaxQBQ8NE86.
PaxDbQ8NE86.
PeptideAtlasQ8NE86.
PRIDEQ8NE86.

Protocols and materials databases

DNASU90550.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357157; ENSP00000349680; ENSG00000156026. [Q8NE86-2]
ENST00000373053; ENSP00000362144; ENSG00000156026. [Q8NE86-1]
ENST00000536019; ENSP00000440913; ENSG00000156026. [Q8NE86-3]
GeneID90550.
KEGGhsa:90550.
UCSCuc001jtc.3. human. [Q8NE86-1]
uc001jtd.3. human. [Q8NE86-3]
uc009xqr.3. human. [Q8NE86-2]

Organism-specific databases

CTD90550.
GeneCardsGC10P074452.
HGNCHGNC:23526. MCU.
HPAHPA016480.
MIM614197. gene.
neXtProtNX_Q8NE86.
PharmGKBPA134888841.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243091.
HOGENOMHOG000008081.
HOVERGENHBG060246.
InParanoidQ8NE86.
OMAKTRFDLE.
OrthoDBEOG7HF1JN.
PhylomeDBQ8NE86.
TreeFamTF314435.

Gene expression databases

BgeeQ8NE86.
CleanExHS_CCDC109A.
GenevestigatorQ8NE86.

Family and domain databases

InterProIPR006769. Coiled-coil-dom_prot_109_C.
[Graphical view]
PfamPF04678. DUF607. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMCU. human.
GenomeRNAi90550.
NextBio76829.
PROQ8NE86.
SOURCESearch...

Entry information

Entry nameMCU_HUMAN
AccessionPrimary (citable) accession number: Q8NE86
Secondary accession number(s): B2RDF3, B3KXV7, Q96FL3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM