Q8NE86 (MCU_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium uniporter protein, mitochondrial

Alternative name(s):
Coiled-coil domain-containing protein 109A

Gene names

Name:	MCU
Synonyms:	C10orf42, CCDC109A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondrion. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. 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
Subunit structure	Homooligomer. Interacts with MICU1; MICU1 acts as an essential gatekeeper for MCU. Interacts with CCDC90A/MCUR1; interaction with MICU1 and CCDC90A/MCUR1 are mutually exclusive. Ref.7 Ref.8 Ref.10
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein Ref.6 Ref.7.
Sequence similarities	Belongs to the MCU family.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Ion channel
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-mediated signaling Inferred from direct assay Ref.7Ref.6. Source: UniProtKB elevation of mitochondrial calcium ion concentration Inferred from direct assay Ref.6. Source: UniProtKB glucose homeostasis Inferred from mutant phenotype Ref.11. Source: UniProtKB mitochondrial calcium ion transport Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of insulin secretion Inferred from mutant phenotype Ref.11. Source: UniProtKB protein complex oligomerization Inferred from direct assay Ref.7. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Inferred from direct assay Ref.7Ref.6. Source: UniProtKB
Molecular_function	calcium channel activity Inferred from direct assay Ref.6. Source: UniProtKB uniporter activity Inferred from direct assay Ref.7Ref.6. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 351	351	Calcium uniporter protein, mitochondrial		PRO_0000282976
Regions
	Topological domain	1 – 233	233	Mitochondrial matrix Potential
	Transmembrane	234 – 256	23	Helical; Potential
	Topological domain	257 – 265	9	Mitochondrial intermembrane Potential
	Transmembrane	266 – 283	18	Helical; Potential
	Topological domain	284 – 351	68	Mitochondrial matrix Potential
	Coiled coil	192 – 223	32	Potential
	Coiled coil	311 – 339	29	Potential
Natural variations
	Alternative sequence	1 – 50	50	MAAAA…QHHRT → M in isoform 3.		VSP_041687
	Alternative sequence	166 – 219	54	DLLSH…APLEK → VEMGFCHVGQNGFELLTSSY LPASASQSAEIIA in isoform 2.		VSP_024263
Experimental info
	Mutagenesis	257	1	E → A: Inhibits calcium uptake. Ref.7
	Mutagenesis	259	1	S → A: Does not inhibit calcium uptake. Ref.7
	Mutagenesis	261	1	D → A: Inhibits calcium uptake. Inhibits calcium channel activity; when associated with Q-264. Ref.6 Ref.7
	Mutagenesis	264	1	E → A: Inhibits calcium uptake. Inhibits calcium channel activity; when associated with Q-261. Ref.6 Ref.7
	Sequence conflict	107	1	S → P in BAG37900. Ref.1
	Sequence conflict	142	1	D → Y in BAG37900. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 50205D01055D66E4	FASTA	351	39,867
	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
	Isoform 2 [UniParc]. Checksum: 56D458541240604A	FASTA	330	36,996
	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 RPPKRVEMGF CHVGQNGFEL 190 200 210 220 230 240 LTSSYLPASA SQSAEIIAVR IEISRKAEKR TTLVLWGGLA YMATQFGILA RLTWWEYSWD 250 260 270 280 290 300 IMEPVTYFIT YGSAMAMYAY FVMTRQEYVY PEARDRQYLL FFHKGAKKSR FDLEKYNQLK 310 320 330 DAIAQAEMDL KRLRDPLQVH LPLRQIGEKD
	Isoform 3 [UniParc]. Checksum: 65C6D99CD9D2D3FC	FASTA	302	35,159
	10 20 30 40 50 60 MVHQRIASWQ NLGAVYCSTV VPSDDVTVVY QNGLPVISVR LPSRRERCQF TLKPISDSVG 70 80 90 100 110 120 VFLRQLQEED RGIDRVAIYS PDGVRVAAST GIDLLLLDDF KLVINDLTYH VRPPKRDLLS 130 140 150 160 170 180 HENAATLNDV KTLVQQLYTT LCIEQHQLNK ERELIERLED LKEQLAPLEK VRIEISRKAE 190 200 210 220 230 240 KRTTLVLWGG LAYMATQFGI LARLTWWEYS WDIMEPVTYF ITYGSAMAMY AYFVMTRQEY 250 260 270 280 290 300 VYPEARDRQY LLFFHKGAKK SRFDLEKYNQ LKDAIAQAEM DLKRLRDPLQ VHLPLRQIGE KD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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 CCDC90A 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.
+	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.
IPI	IPI00171573. IPI00185975. IPI01011042.
RefSeq	NP_001257608.1. NM_001270679.1. NP_001257609.1. NM_001270680.1. NP_612366.1. NM_138357.2.
UniGene	Hs.591366.
3D structure databases
ProteinModelPortal	Q8NE86.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362144.
PTM databases
PhosphoSite	Q8NE86.
Polymorphism databases
DMDM	74730222.
Proteomic databases
PaxDb	Q8NE86.
PeptideAtlas	Q8NE86.
PRIDE	Q8NE86.
Protocols and materials databases
DNASU	90550.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357157; ENSP00000349680; ENSG00000156026. ENST00000373053; ENSP00000362144; ENSG00000156026. ENST00000536019; ENSP00000440913; ENSG00000156026.
GeneID	90550.
KEGG	hsa:90550.
UCSC	uc001jtc.3. human. uc001jtd.3. human. uc009xqr.3. human.
Organism-specific databases
CTD	90550.
GeneCards	GC10P074452.
HGNC	HGNC:23526. MCU.
HPA	HPA016480.
MIM	614197. gene.
neXtProt	NX_Q8NE86.
PharmGKB	PA134888841.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG243091.
HOGENOM	HOG000008081.
HOVERGEN	HBG060246.
InParanoid	Q8NE86.
OMA	TLRIEEH.
OrthoDB	EOG4Z8XX3.
PhylomeDB	Q8NE86.
Gene expression databases
Bgee	Q8NE86.
CleanEx	HS_CCDC109A.
Genevestigator	Q8NE86.
Family and domain databases
InterPro	IPR006769. Coiled-coil-dom_prot_109_C. [Graphical view]
Pfam	PF04678. DUF607. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MCU. human.
GenomeRNAi	90550.
NextBio	76829.
SOURCE	Search...

Entry information

Entry name

MCU_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.