ID MCU_HUMAN Reviewed; 351 AA. AC Q8NE86; B2RDF3; B3KXV7; Q96FL3; DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 160. DE RecName: Full=Calcium uniporter protein, mitochondrial {ECO:0000303|PubMed:21685886}; DE Short=HsMCU {ECO:0000303|PubMed:27135929}; DE AltName: Full=Coiled-coil domain-containing protein 109A {ECO:0000305}; DE Flags: Precursor; GN Name=MCU {ECO:0000303|PubMed:21685886, ECO:0000312|HGNC:HGNC:23526}; GN Synonyms=C10orf42 {ECO:0000312|HGNC:HGNC:23526}, CCDC109A GN {ECO:0000312|HGNC:HGNC:23526}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Testis, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye, and Testis; 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 [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [6] RP FUNCTION, MUTAGENESIS OF 261-ASP--GLU-264, SUBCELLULAR LOCATION, AND TISSUE RP 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, OLIGOMERIZATION, SUBUNIT, INTERACTION WITH MICU1, MUTAGENESIS OF RP GLU-257; SER-259 AND 261-ASP--GLU-264, AND SUBCELLULAR LOCATION. 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 [8] RP FUNCTION, AND INTERACTION WITH MICU1. RX PubMed=23101630; DOI=10.1016/j.cell.2012.10.011; RA Mallilankaraman K., Doonan P., Cardenas C., Chandramoorthy H.C., Muller M., RA Miller R., Hoffman N.E., Gandhirajan R.K., Molgo J., Birnbaum M.J., RA Rothberg B.S., Mak D.O., Foskett J.K., Madesh M.; RT "MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) RT uptake that regulates cell survival."; RL Cell 151:630-644(2012). RN [9] RP FUNCTION. RX PubMed=22904319; DOI=10.1074/jbc.m112.392084; RA Alam M.R., Groschner L.N., Parichatikanond W., Kuo L., Bondarenko A.I., RA Rost R., Waldeck-Weiermair M., Malli R., Graier W.F.; RT "Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) RT contribute to metabolism-secretion coupling in clonal pancreatic beta- RT cells."; RL J. Biol. Chem. 287:34445-34454(2012). RN [10] RP PHOSPHORYLATION AT SER-57 AND SER-92, AND MUTAGENESIS OF SER-57 AND SER-92. RX PubMed=23051746; DOI=10.1038/nature11444; RA Joiner M.L., Koval O.M., Li J., He B.J., Allamargot C., Gao Z., RA Luczak E.D., Hall D.D., Fink B.D., Chen B., Yang J., Moore S.A., RA Scholz T.D., Strack S., Mohler P.J., Sivitz W.I., Song L.S., Anderson M.E.; RT "CaMKII determines mitochondrial stress responses in heart."; RL Nature 491:269-273(2012). RN [11] RP FUNCTION, AND INTERACTION WITH MCUR1 AND MICU1. RX PubMed=23178883; DOI=10.1038/ncb2622; RA Mallilankaraman K., Cardenas C., Doonan P.J., Chandramoorthy H.C., RA Irrinki K.M., Golenar T., Csordas G., Madireddi P., Yang J., Muller M., RA Miller R., Kolesar J.E., Molgo J., Kaufman B., Hajnoczky G., Foskett J.K., RA Madesh M.; RT "MCUR1 is an essential component of mitochondrial Ca(2+) uptake that RT regulates cellular metabolism."; RL Nat. Cell Biol. 14:1336-1343(2012). RN [12] RP FUNCTION. RX PubMed=22829870; DOI=10.1371/journal.pone.0039722; RA Tarasov A.I., Semplici F., Ravier M.A., Bellomo E.A., Pullen T.J., RA Gilon P., Sekler I., Rizzuto R., Rutter G.A.; RT "The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP RT increases in pancreatic beta-cells."; RL PLoS ONE 7:E39722-E39722(2012). RN [13] RP FUNCTION. RX PubMed=22822213; DOI=10.1073/pnas.1210718109; RA Drago I., De Stefani D., Rizzuto R., Pozzan T.; RT "Mitochondrial Ca2+ uptake contributes to buffering cytoplasmic Ca2+ peaks RT in cardiomyocytes."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12986-12991(2012). RN [14] RP IDENTIFICATION. RX PubMed=22605770; DOI=10.1126/science.1214977; RA Bick A.G., Calvo S.E., Mootha V.K.; RT "Evolutionary diversity of the mitochondrial calcium uniporter."; RL Science 336:886-886(2012). RN [15] RP FUNCTION, AND INTERACTION WITH MICU1. RX PubMed=24332854; DOI=10.1016/j.celrep.2013.11.026; RA Hoffman N.E., Chandramoorthy H.C., Shamugapriya S., Zhang X., Rajan S., RA Mallilankaraman K., Gandhirajan R.K., Vagnozzi R.J., Ferrer L.M., RA Sreekrishnanilayam K., Natarajaseenivasan K., Vallem S., Force T., RA Choi E.T., Cheung J.Y., Madesh M.; RT "MICU1 motifs define mitochondrial calcium uniporter binding and RT activity."; RL Cell Rep. 5:1576-1588(2013). RN [16] RP INDUCTION. RX PubMed=23246404; DOI=10.1016/j.cub.2012.11.026; RA Marchi S., Lupini L., Patergnani S., Rimessi A., Missiroli S., Bonora M., RA Bononi A., Corra F., Giorgi C., De Marchi E., Poletti F., Gafa R., RA Lanza G., Negrini M., Rizzuto R., Pinton P.; RT "Downregulation of the mitochondrial calcium uniporter by cancer-related RT miR-25."; RL Curr. Biol. 23:58-63(2013). RN [17] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP SER-259. RX PubMed=23755363; DOI=10.7554/elife.00704; RA Chaudhuri D., Sancak Y., Mootha V.K., Clapham D.E.; RT "MCU encodes the pore conducting mitochondrial calcium currents."; RL Elife 2:E00704-E00704(2013). RN [18] RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE UNIPLEX COMPLEX. RX PubMed=24231807; DOI=10.1126/science.1242993; RA Sancak Y., Markhard A.L., Kitami T., Kovacs-Bogdan E., Kamer K.J., RA Udeshi N.D., Carr S.A., Chaudhuri D., Clapham D.E., Li A.A., Calvo S.E., RA Goldberger O., Mootha V.K.; RT "EMRE is an essential component of the mitochondrial calcium uniporter RT complex."; RL Science 342:1379-1382(2013). RN [19] RP PHOSPHORYLATION. RX PubMed=24800979; DOI=10.1089/ars.2013.5394; RA O-Uchi J., Jhun B.S., Xu S., Hurst S., Raffaello A., Liu X., Yi B., RA Zhang H., Gross P., Mishra J., Ainbinder A., Kettlewell S., Smith G.L., RA Dirksen R.T., Wang W., Rizzuto R., Sheu S.S.; RT "Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2- RT dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter."; RL Antioxid. Redox Signal. 21:863-879(2014). RN [20] RP INTERACTION WITH SLC25A23. RX PubMed=24430870; DOI=10.1091/mbc.e13-08-0502; RA Hoffman N.E., Chandramoorthy H.C., Shanmughapriya S., Zhang X.Q., RA Vallem S., Doonan P.J., Malliankaraman K., Guo S., Rajan S., Elrod J.W., RA Koch W.J., Cheung J.Y., Madesh M.; RT "SLC25A23 augments mitochondrial Ca(2+) uptake, interacts with MCU, and RT induces oxidative stress-mediated cell death."; RL Mol. Biol. Cell 25:936-947(2014). RN [21] RP FUNCTION. RX PubMed=24560927; DOI=10.1016/j.molcel.2014.01.013; RA Patron M., Checchetto V., Raffaello A., Teardo E., Vecellio Reane D., RA Mantoan M., Granatiero V., Szabo I., De Stefani D., Rizzuto R.; RT "MICU1 and MICU2 finely tune the mitochondrial Ca(2+) uniporter by exerting RT opposite effects on MCU activity."; RL Mol. Cell 53:726-737(2014). RN [22] RP COMMENT ON PUBMED:23051746 RESULTS. RX PubMed=25254480; DOI=10.1038/nature13626; RA Fieni F., Johnson D.E., Hudmon A., Kirichok Y.; RT "Mitochondrial Ca2+ uniporter and CaMKII in heart."; RL Nature 513:E1-E2(2014). RN [23] RP COMMENT ON PUBMED:25254480 RESULTS. RX PubMed=25254481; DOI=10.1038/nature13627; RA Joiner M.L., Koval O.M., Li J., He B.J., Allamargot C., Gao Z., RA Luczak E.D., Hall D.D., Fink B.D., Chen B., Yang J., Moore S.A., RA Scholz T.D., Strack S., Mohler P.J., Sivitz W.I., Song L.S., Anderson M.E.; RT "Joiner et al. reply."; RL Nature 513:E3-E3(2014). RN [24] RP INDUCTION. RX PubMed=25764156; DOI=10.3390/ijms16035420; RA Pan L., Huang B.J., Ma X.E., Wang S.Y., Feng J., Lv F., Liu Y., Liu Y., RA Li C.M., Liang D.D., Li J., Xu L., Chen Y.H.; RT "MiR-25 protects cardiomyocytes against oxidative damage by targeting the RT mitochondrial calcium uniporter."; RL Int. J. Mol. Sci. 16:5420-5433(2015). RN [25] RP FUNCTION, AND MUTAGENESIS OF 261-ASP--GLU-264. 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 [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [27] RP FUNCTION. RX PubMed=26903221; DOI=10.1016/j.bbamem.2016.02.022; RA Matesanz-Isabel J., Arias-Del-Val J., Alvarez-Illera P., Fonteriz R.I., RA Montero M., Alvarez J.; RT "Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake."; RL Biochim. Biophys. Acta 1858:1110-1117(2016). RN [28] RP INTERACTION WITH MCUR1 AND CCDC90B. RX PubMed=27184846; DOI=10.1016/j.celrep.2016.04.050; RA Tomar D., Dong Z., Shanmughapriya S., Koch D.A., Thomas T., Hoffman N.E., RA Timbalia S.A., Goldman S.J., Breves S.L., Corbally D.P., Nemani N., RA Fairweather J.P., Cutri A.R., Zhang X., Song J., Jana F., Huang J., RA Barrero C., Rabinowitz J.E., Luongo T.S., Schumacher S.M., Rockman M.E., RA Dietrich A., Merali S., Caplan J., Stathopulos P., Ahima R.S., Cheung J.Y., RA Houser S.R., Koch W.J., Patel V., Gohil V.M., Elrod J.W., Rajan S., RA Madesh M.; RT "MCUR1 is a scaffold factor for the MCU complex function and promotes RT mitochondrial bioenergetics."; RL Cell Rep. 15:1673-1685(2016). RN [29] RP FUNCTION, AND TOPOLOGY. RX PubMed=27099988; DOI=10.7554/elife.15545; RA Tsai M.F., Phillips C.B., Ranaghan M., Tsai C.W., Wu Y., Willliams C., RA Miller C.; RT "Dual functions of a small regulatory subunit in the mitochondrial calcium RT uniporter complex."; RL Elife 5:0-0(2016). RN [30] RP MUTAGENESIS OF GLU-257; SER-259; ASP-261 AND GLU-264. RX PubMed=27135929; DOI=10.1038/nature17656; RA Oxenoid K., Dong Y., Cao C., Cui T., Sancak Y., Markhard A.L., Grabarek Z., RA Kong L., Liu Z., Ouyang B., Cong Y., Mootha V.K., Chou J.J.; RT "Architecture of the mitochondrial calcium uniporter."; RL Nature 533:269-273(2016). RN [31] RP INTERACTION WITH MCUR1. RX PubMed=26976564; DOI=10.1073/pnas.1602264113; RA Chaudhuri D., Artiga D.J., Abiria S.A., Clapham D.E.; RT "Mitochondrial calcium uniporter regulator 1 (MCUR1) regulates the calcium RT threshold for the mitochondrial permeability transition."; RL Proc. Natl. Acad. Sci. U.S.A. 113:E1872-E1880(2016). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 75-185, FUNCTION, SUBUNIT, RP INTERACTION WITH MCUR1; MICU1 AND MICU2, SUBCELLULAR LOCATION, MUTAGENESIS RP OF SER-92 AND LYS-180, AND DOMAIN. RX PubMed=26341627; DOI=10.15252/embr.201540436; RA Lee Y., Min C.K., Kim T.G., Song H.K., Lim Y., Kim D., Shin K., Kang M., RA Kang J.Y., Youn H.S., Lee J.G., An J.Y., Park K.R., Lim J.J., Kim J.H., RA Kim J.H., Park Z.Y., Kim Y.S., Wang J., Kim D.H., Eom S.H.; RT "Structure and function of the N-terminal domain of the human mitochondrial RT calcium uniporter."; RL EMBO Rep. 16:1318-1333(2015). CC -!- FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates CC calcium uptake into mitochondria (PubMed:21685888, PubMed:21685886, CC PubMed:23101630, PubMed:22904319, PubMed:23178883, PubMed:22829870, CC PubMed:22822213, PubMed:24332854, PubMed:23755363, PubMed:26341627). CC Constitutes the pore-forming and calcium-conducting subunit of the CC uniporter complex (uniplex) (PubMed:23755363). Activity is regulated by CC MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by CC MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity CC (PubMed:24560927, PubMed:26903221). Mitochondrial calcium homeostasis CC plays key roles in cellular physiology and regulates cell CC bioenergetics, cytoplasmic calcium signals and activation of cell death CC pathways. Involved in buffering the amplitude of systolic calcium rises CC in cardiomyocytes (PubMed:22822213). While dispensable for baseline CC homeostatic cardiac function, acts as a key regulator of short-term CC mitochondrial calcium loading underlying a 'fight-or-flight' response CC during acute stress: acts by mediating a rapid increase of CC mitochondrial calcium in pacemaker cells (PubMed:25603276). CC participates in mitochondrial permeability transition during ischemia- CC reperfusion injury (By similarity). Regulates glucose-dependent insulin CC secretion in pancreatic beta-cells by regulating mitochondrial calcium CC uptake (PubMed:22904319, PubMed:22829870). Mitochondrial calcium uptake CC in skeletal muscle cells is involved in muscle size in adults (By CC similarity). Regulates synaptic vesicle endocytosis kinetics in central CC nerve terminal (By similarity). Involved in antigen processing and CC presentation (By similarity). {ECO:0000250|UniProtKB:Q3UMR5, CC ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:21685888, CC ECO:0000269|PubMed:22822213, ECO:0000269|PubMed:22829870, CC ECO:0000269|PubMed:22904319, ECO:0000269|PubMed:23101630, CC ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:23755363, CC ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24560927, CC ECO:0000269|PubMed:25603276, ECO:0000269|PubMed:26341627, CC ECO:0000269|PubMed:26903221}. CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative CC Ru360. {ECO:0000269|PubMed:23755363}. CC -!- SUBUNIT: Component of the uniplex complex, composed of MCU, MCUB, CC MICU1, MICU2 and EMRE/SMDT1 (PubMed:24231807). Homooligomer CC (PubMed:21685886, PubMed:26341627). Forms a pentamer (By similarity). CC Heterooligomer with CCDC109B/MCUB; this inhibits channel activity (By CC similarity). Interacts with MICU1; MICU1 acts as an essential regulator CC for MCU (PubMed:21685886, PubMed:23101630, PubMed:23178883, CC PubMed:24332854, PubMed:26341627). Interacts with MCUR1 CC (PubMed:23178883, PubMed:26341627, PubMed:27184846, PubMed:26976564). CC Interacts with CCDC90B (PubMed:27184846). Interactions with MICU1 and CC MCUR1 are mutually exclusive (PubMed:23178883). Interacts with MICU2 CC (PubMed:26341627). Interacts with SLC25A23 (PubMed:24430870). CC {ECO:0000250|UniProtKB:Q21121, ECO:0000250|UniProtKB:Q3UMR5, CC ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:23101630, CC ECO:0000269|PubMed:23178883, ECO:0000269|PubMed:24231807, CC ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24430870, CC ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26976564, CC ECO:0000269|PubMed:27184846}. CC -!- INTERACTION: CC Q8NE86; Q9BPX6: MICU1; NbExp=7; IntAct=EBI-6552124, EBI-2371996; CC Q8NE86; Q9H4I9: SMDT1; NbExp=7; IntAct=EBI-6552124, EBI-11908005; CC Q8NE86-1; Q8NE86-1: MCU; NbExp=2; IntAct=EBI-15932889, EBI-15932889; CC Q8NE86-1; Q96AQ8: MCUR1; NbExp=4; IntAct=EBI-15932889, EBI-14404755; CC Q8NE86-1; Q9BPX6: MICU1; NbExp=2; IntAct=EBI-15932889, EBI-2371996; CC Q8NE86-1; Q9BPX6-1: MICU1; NbExp=2; IntAct=EBI-15932889, EBI-5456336; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:21685886, ECO:0000269|PubMed:21685888, CC ECO:0000269|PubMed:23755363, ECO:0000269|PubMed:24231807, CC ECO:0000269|PubMed:27099988, ECO:0000305|PubMed:26341627}; Multi-pass CC membrane protein {ECO:0000269|PubMed:21685886, CC ECO:0000269|PubMed:21685888, ECO:0000269|PubMed:24231807}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8NE86-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NE86-2; Sequence=VSP_024263; CC Name=3; CC IsoId=Q8NE86-3; Sequence=VSP_041687; CC -!- INDUCTION: MCU transcripts are down-regulated by microRNA miR-25 CC (PubMed:23246404). Down-regulation by miR-25 may protect cardiomyocytes CC against oxidative damage in cardiomyocytes (PubMed:25764156). CC {ECO:0000269|PubMed:23246404, ECO:0000269|PubMed:25764156}. CC -!- DOMAIN: The N-terminal MCU domain is required for efficient Ca(2+) CC uptake and for interaction with MCUR1. It is not required for targeting CC to the mitochondria, oligomerization, interaction with MICU1 and MICU2, CC or assembly of the uniplex complex. {ECO:0000269|PubMed:26341627}. 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 (PubMed:23051746, PubMed:25254481). The regulation of MCU by CaMK2 is CC however subject to discussion: another group was unable to reproduce CC these results (PubMed:25254480). Phosphorylated on tyrosines by CC PTK2B/PYK2, promoting oligomerization (PubMed:24800979). CC {ECO:0000269|PubMed:24800979, ECO:0000305|PubMed:23051746, CC ECO:0000305|PubMed:25254480, ECO:0000305|PubMed:25254481}. CC -!- SIMILARITY: Belongs to the MCU (TC 1.A.77) family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK315519; BAG37900.1; -; mRNA. DR EMBL; AK128016; BAG54619.1; -; mRNA. DR EMBL; AC016542; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069548; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471083; EAW54461.1; -; Genomic_DNA. DR EMBL; BC010682; AAH10682.1; -; mRNA. DR EMBL; BC034235; AAH34235.1; -; mRNA. DR CCDS; CCDS59218.1; -. [Q8NE86-2] DR CCDS; CCDS59219.1; -. [Q8NE86-3] DR CCDS; CCDS7317.1; -. [Q8NE86-1] DR RefSeq; NP_001257608.1; NM_001270679.1. [Q8NE86-2] DR RefSeq; NP_001257609.1; NM_001270680.1. [Q8NE86-3] DR RefSeq; NP_612366.1; NM_138357.2. [Q8NE86-1] DR PDB; 4XSJ; X-ray; 1.80 A; A=75-165. DR PDB; 4XTB; X-ray; 1.50 A; A=75-185. DR PDB; 5BZ6; X-ray; 2.75 A; A=75-165. DR PDB; 5KUE; X-ray; 1.50 A; A=72-189. DR PDB; 5KUG; X-ray; 1.90 A; A=72-189. DR PDB; 5KUI; X-ray; 2.70 A; A=72-189. DR PDB; 5KUJ; X-ray; 1.60 A; A=72-189. DR PDB; 6JG0; X-ray; 2.50 A; A=75-165. DR PDB; 6K7X; EM; 3.27 A; A/B/C/D/K/L/M/N=73-348. DR PDB; 6K7Y; EM; 3.60 A; A/B/C/D/N/O/P/Q=73-348. DR PDB; 6KVX; X-ray; 2.85 A; A=75-164. DR PDB; 6O58; EM; 3.80 A; A/C/E/G/I/K/M/O=1-351. DR PDB; 6O5B; EM; 3.60 A; A/C/E/G/I/J/K/L=1-351. DR PDB; 6WDN; EM; 3.20 A; C/E/G/I=169-346. DR PDB; 6WDO; EM; 3.60 A; A/E/G/I/M/O=74-346, C/K=74-341. DR PDB; 6XJV; EM; 4.17 A; A/C/E/G/I/K/M/O=1-351. DR PDB; 6XJX; EM; 4.60 A; A/C/E/G=1-351. DR PDBsum; 4XSJ; -. DR PDBsum; 4XTB; -. DR PDBsum; 5BZ6; -. DR PDBsum; 5KUE; -. DR PDBsum; 5KUG; -. DR PDBsum; 5KUI; -. DR PDBsum; 5KUJ; -. DR PDBsum; 6JG0; -. DR PDBsum; 6K7X; -. DR PDBsum; 6K7Y; -. DR PDBsum; 6KVX; -. DR PDBsum; 6O58; -. DR PDBsum; 6O5B; -. DR PDBsum; 6WDN; -. DR PDBsum; 6WDO; -. DR PDBsum; 6XJV; -. DR PDBsum; 6XJX; -. DR AlphaFoldDB; Q8NE86; -. DR EMDB; EMD-0625; -. DR EMDB; EMD-0626; -. DR EMDB; EMD-0627; -. DR EMDB; EMD-21642; -. DR EMDB; EMD-21643; -. DR EMDB; EMD-22215; -. DR EMDB; EMD-22216; -. DR EMDB; EMD-9944; -. DR EMDB; EMD-9945; -. DR SMR; Q8NE86; -. DR BioGRID; 124733; 198. DR ComplexPortal; CPX-5961; Mitochondrial calcium uniporter complex, MICU1-MICU2 variant. DR ComplexPortal; CPX-5963; Mitochondrial calcium uniporter complex, MICU1 variant. DR ComplexPortal; CPX-5965; Mitochondrial calcium uniporter complex, MICU1-MICU3 variant. DR ComplexPortal; CPX-5966; Mitochondrial calcium uniporter complex, MICUB variant. DR CORUM; Q8NE86; -. DR DIP; DIP-60468N; -. DR IntAct; Q8NE86; 34. DR MINT; Q8NE86; -. DR STRING; 9606.ENSP00000362144; -. DR GlyGen; Q8NE86; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8NE86; -. DR MetOSite; Q8NE86; -. DR PhosphoSitePlus; Q8NE86; -. DR SwissPalm; Q8NE86; -. DR BioMuta; MCU; -. DR DMDM; 74730222; -. DR EPD; Q8NE86; -. DR jPOST; Q8NE86; -. DR MassIVE; Q8NE86; -. DR MaxQB; Q8NE86; -. DR PaxDb; 9606-ENSP00000362144; -. DR PeptideAtlas; Q8NE86; -. DR ProteomicsDB; 73134; -. [Q8NE86-1] DR ProteomicsDB; 73135; -. [Q8NE86-2] DR ProteomicsDB; 73136; -. [Q8NE86-3] DR Pumba; Q8NE86; -. DR TopDownProteomics; Q8NE86-3; -. [Q8NE86-3] DR Antibodypedia; 3091; 116 antibodies from 21 providers. DR DNASU; 90550; -. DR Ensembl; ENST00000357157.10; ENSP00000349680.6; ENSG00000156026.15. [Q8NE86-2] DR Ensembl; ENST00000373053.8; ENSP00000362144.3; ENSG00000156026.15. [Q8NE86-1] DR Ensembl; ENST00000536019.5; ENSP00000440913.1; ENSG00000156026.15. [Q8NE86-3] DR GeneID; 90550; -. DR KEGG; hsa:90550; -. DR MANE-Select; ENST00000373053.8; ENSP00000362144.3; NM_138357.3; NP_612366.1. DR UCSC; uc001jtc.3; human. [Q8NE86-1] DR AGR; HGNC:23526; -. DR CTD; 90550; -. DR DisGeNET; 90550; -. DR GeneCards; MCU; -. DR HGNC; HGNC:23526; MCU. DR HPA; ENSG00000156026; Tissue enhanced (tongue). DR MIM; 614197; gene. DR neXtProt; NX_Q8NE86; -. DR OpenTargets; ENSG00000156026; -. DR PharmGKB; PA134888841; -. DR VEuPathDB; HostDB:ENSG00000156026; -. DR eggNOG; KOG2966; Eukaryota. DR GeneTree; ENSGT00940000157528; -. DR HOGENOM; CLU_056554_0_0_1; -. DR InParanoid; Q8NE86; -. DR OMA; DDIYVEY; -. DR OrthoDB; 469277at2759; -. DR PhylomeDB; Q8NE86; -. DR TreeFam; TF314435; -. DR PathwayCommons; Q8NE86; -. DR Reactome; R-HSA-8949215; Mitochondrial calcium ion transport. DR Reactome; R-HSA-8949664; Processing of SMDT1. DR SignaLink; Q8NE86; -. DR SIGNOR; Q8NE86; -. DR BioGRID-ORCS; 90550; 11 hits in 1158 CRISPR screens. DR ChiTaRS; MCU; human. DR GenomeRNAi; 90550; -. DR Pharos; Q8NE86; Tbio. DR PRO; PR:Q8NE86; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q8NE86; Protein. DR Bgee; ENSG00000156026; Expressed in tibialis anterior and 154 other cell types or tissues. DR ExpressionAtlas; Q8NE86; baseline and differential. DR GO; GO:0034704; C:calcium channel complex; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:1990246; C:uniplex complex; IDA:UniProtKB. DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0015292; F:uniporter activity; IDA:UniProtKB. DR GO; GO:0036444; P:calcium import into the mitochondrion; IDA:MGI. DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IDA:ComplexPortal. DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:UniProtKB. DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IDA:UniProtKB. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IMP:CACAO. DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:CACAO. DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB. DR InterPro; IPR006769; MCU_C. DR InterPro; IPR039055; MCU_fam. DR PANTHER; PTHR13462; CALCIUM UNIPORTER PROTEIN, MITOCHONDRIAL; 1. DR PANTHER; PTHR13462:SF16; CALCIUM UNIPORTER PROTEIN, MITOCHONDRIAL; 1. DR Pfam; PF04678; MCU; 1. DR Genevisible; Q8NE86; HS. PE 1: Evidence at protein level; KW 3D-structure; 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..50 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 51..351 FT /note="Calcium uniporter protein, mitochondrial" FT /id="PRO_0000282976" FT TOPO_DOM 51..233 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27099988" FT TRANSMEM 234..256 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 257..265 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27099988" FT TRANSMEM 266..283 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 284..351 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000269|PubMed:23755363, FT ECO:0000305|PubMed:27099988" FT REGION 75..165 FT /note="N-terminal MCU domain" FT /evidence="ECO:0000269|PubMed:26341627" FT REGION 216..234 FT /note="Outer juxtamembrane helix (OJMH)" FT /evidence="ECO:0000250|UniProtKB:Q21121" FT REGION 283..292 FT /note="Inner juxtamembrane helix (IJMH)" FT /evidence="ECO:0000250|UniProtKB:Q21121" FT COILED 192..223 FT /evidence="ECO:0000255" FT COILED 311..339 FT /evidence="ECO:0000255" FT MOTIF 261..264 FT /note="DXXE" FT /evidence="ECO:0000250|UniProtKB:Q21121" FT MOD_RES 57 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000305|PubMed:23051746" FT MOD_RES 92 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000305|PubMed:23051746" FT MOD_RES 332 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q3UMR5" FT VAR_SEQ 1..50 FT /note="MAAAAGRSLLLLLSSRGGGGGGAGGCGALTAGCFPGLGVSRHRQQQHHRT FT -> M (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041687" FT VAR_SEQ 166..219 FT /note="DLLSHENAATLNDVKTLVQQLYTTLCIEQHQLNKERELIERLEDLKEQLAPL FT EK -> VEMGFCHVGQNGFELLTSSYLPASASQSAEIIA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024263" FT MUTAGEN 57 FT /note="S->A: Decreased MCU current; when associated with FT A-92." FT /evidence="ECO:0000269|PubMed:23051746" FT MUTAGEN 92 FT /note="S->A: Decreased MCU current; when associated with FT A-57." FT /evidence="ECO:0000269|PubMed:23051746" FT MUTAGEN 92 FT /note="S->A: Impairs Ca(2+) uptake, but has no effect on FT oligomerization and interaction with MCU1 and MCU2." FT /evidence="ECO:0000269|PubMed:26341627" FT MUTAGEN 180 FT /note="K->A: No effect on Ca(2+) uptake, oligomerization FT and interaction with MCU1 and MCU2." FT /evidence="ECO:0000269|PubMed:26341627" FT MUTAGEN 257 FT /note="E->A: According to a report, inhibits calcium FT uptake. According to a subsequent report, does not affect FT greatly calcium uptake." FT /evidence="ECO:0000269|PubMed:21685886, FT ECO:0000269|PubMed:27135929" FT MUTAGEN 257 FT /note="E->S: Does not affect greatly calcium uptake." FT /evidence="ECO:0000269|PubMed:27135929" FT MUTAGEN 259 FT /note="S->A: Does not inhibit calcium uptake. Strongly FT reduced sensitivity to ruthenium red inhibition." FT /evidence="ECO:0000269|PubMed:21685886, FT ECO:0000269|PubMed:23755363" FT MUTAGEN 259 FT /note="S->R: Prevents entrance of calcium into the pore." FT /evidence="ECO:0000269|PubMed:27135929" FT MUTAGEN 261..264 FT /note="DIME->AIMA: Dominant negative (DN) mutant; inhibits FT calcium uptake. Inhibits calcium channel activity. FT Expression of the dominant negative protein in mice, leads FT to mice that are incapable of physiological fight or flight FT heart rate acceleration." FT /evidence="ECO:0000269|PubMed:21685886, FT ECO:0000269|PubMed:21685888, ECO:0000269|PubMed:25603276" FT MUTAGEN 261 FT /note="D->E: Partially functional; does not completely FT abolish calcium channel activity." FT /evidence="ECO:0000269|PubMed:27135929" FT MUTAGEN 264 FT /note="E->D: Abolishes calcium channel activity." FT /evidence="ECO:0000269|PubMed:27135929" FT CONFLICT 107 FT /note="S -> P (in Ref. 1; BAG37900)" FT /evidence="ECO:0000305" FT CONFLICT 142 FT /note="D -> Y (in Ref. 1; BAG37900)" FT /evidence="ECO:0000305" FT STRAND 76..80 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 83..88 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:5KUI" FT STRAND 97..100 FT /evidence="ECO:0007829|PDB:4XTB" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:4XTB" FT HELIX 108..118 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 137..140 FT /evidence="ECO:0007829|PDB:5KUI" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 149..153 FT /evidence="ECO:0007829|PDB:4XTB" FT STRAND 156..160 FT /evidence="ECO:0007829|PDB:4XTB" FT HELIX 168..172 FT /evidence="ECO:0007829|PDB:4XTB" FT HELIX 175..189 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 192..199 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 201..208 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 210..213 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 216..219 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 221..240 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 242..252 FT /evidence="ECO:0007829|PDB:6WDN" FT TURN 253..255 FT /evidence="ECO:0007829|PDB:6WDN" FT STRAND 256..258 FT /evidence="ECO:0007829|PDB:6WDN" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 265..268 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 271..274 FT /evidence="ECO:0007829|PDB:6WDN" FT TURN 275..279 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 280..285 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 291..310 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 314..329 FT /evidence="ECO:0007829|PDB:6WDN" FT HELIX 331..334 FT /evidence="ECO:0007829|PDB:6WDN" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:6WDN" SQ SEQUENCE 351 AA; 39867 MW; 50205D01055D66E4 CRC64; MAAAAGRSLL LLLSSRGGGG GGAGGCGALT AGCFPGLGVS RHRQQQHHRT VHQRIASWQN LGAVYCSTVV PSDDVTVVYQ NGLPVISVRL PSRRERCQFT LKPISDSVGV FLRQLQEEDR GIDRVAIYSP DGVRVAASTG IDLLLLDDFK LVINDLTYHV RPPKRDLLSH ENAATLNDVK TLVQQLYTTL CIEQHQLNKE RELIERLEDL KEQLAPLEKV RIEISRKAEK RTTLVLWGGL AYMATQFGIL ARLTWWEYSW DIMEPVTYFI TYGSAMAMYA YFVMTRQEYV YPEARDRQYL LFFHKGAKKS RFDLEKYNQL KDAIAQAEMD LKRLRDPLQV HLPLRQIGEK D //