MCU_DICDI
ID MCU_DICDI Reviewed; 275 AA.
AC Q54LT0;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Calcium uniporter protein, mitochondrial;
DE Short=DdMCU {ECO:0000303|PubMed:24889638};
DE Flags: Precursor;
GN ORFNames=DDB0186972 {ECO:0000312|EMBL:EAL64239.1};
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=24889638; DOI=10.1073/pnas.1400514111;
RA Kovacs-Bogdan E., Sancak Y., Kamer K.J., Plovanich M., Jambhekar A.,
RA Huber R.J., Myre M.A., Blower M.D., Mootha V.K.;
RT "Reconstitution of the mitochondrial calcium uniporter in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:8985-8990(2014).
CC -!- FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates
CC calcium uptake into mitochondria (PubMed:24889638). Constitutes a pore-
CC forming and calcium-conducting subunit (PubMed:24889638). Mitochondrial
CC calcium homeostasis plays key roles in cellular physiology and
CC regulates cell bioenergetics, cytoplasmic calcium signals and
CC activation of cell death pathways. {ECO:0000250|UniProtKB:Q8NE86,
CC ECO:0000269|PubMed:24889638}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative
CC Ru360. {ECO:0000269|PubMed:24889638}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:24889638}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24889638}.
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. {ECO:0000250|UniProtKB:Q21121}.
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; AAFI02000085; EAL64239.1; -; Genomic_DNA.
DR RefSeq; XP_637750.1; XM_632658.1.
DR PDB; 5Z2H; X-ray; 1.67 A; A/B=29-126.
DR PDB; 5Z2I; X-ray; 2.14 A; A/B/C/D=29-126.
DR PDBsum; 5Z2H; -.
DR PDBsum; 5Z2I; -.
DR AlphaFoldDB; Q54LT0; -.
DR SMR; Q54LT0; -.
DR STRING; 44689.DDB0186972; -.
DR TCDB; 1.A.77.1.4; the mg(2+)/ca(2+) uniporter (mcu) family.
DR PaxDb; Q54LT0; -.
DR GeneID; 8625616; -.
DR KEGG; ddi:DDB_G0286429; -.
DR dictyBase; DDB_G0286429; mcu.
DR eggNOG; KOG2966; Eukaryota.
DR HOGENOM; CLU_041073_0_0_1; -.
DR InParanoid; Q54LT0; -.
DR OMA; CGLRRFM; -.
DR PhylomeDB; Q54LT0; -.
DR Reactome; R-DDI-8949215; Mitochondrial calcium ion transport.
DR PRO; PR:Q54LT0; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:dictyBase.
DR GO; GO:1990246; C:uniplex complex; IBA:GO_Central.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; TAS:dictyBase.
DR GO; GO:0043621; F:protein self-association; IPI:dictyBase.
DR GO; GO:0015292; F:uniporter activity; IBA:GO_Central.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IMP:dictyBase.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IBA:GO_Central.
DR InterPro; IPR006769; MCU_C.
DR InterPro; IPR039055; MCU_fam.
DR PANTHER; PTHR13462; PTHR13462; 1.
DR Pfam; PF04678; MCU; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Calcium channel; Calcium transport; Coiled coil;
KW Ion channel; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 29..275
FT /note="Calcium uniporter protein, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000437214"
FT TOPO_DOM 29..165
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:24889638"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..192
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:24889638"
FT TRANSMEM 193..213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..275
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:24889638"
FT REGION 147..165
FT /note="Outer juxtamembrane helix (OJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT REGION 214..223
FT /note="Inner juxtamembrane helix (IJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT COILED 125..157
FT /evidence="ECO:0000255"
FT COILED 244..270
FT /evidence="ECO:0000255"
FT MOTIF 192..195
FT /note="DXXE"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT HELIX 31..50
FT /evidence="ECO:0007829|PDB:5Z2H"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:5Z2H"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:5Z2H"
FT HELIX 72..84
FT /evidence="ECO:0007829|PDB:5Z2H"
FT HELIX 97..100
FT /evidence="ECO:0007829|PDB:5Z2H"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:5Z2H"
FT HELIX 108..118
FT /evidence="ECO:0007829|PDB:5Z2H"
SQ SEQUENCE 275 AA; 31756 MW; 6D4C7343C458696D CRC64;
MNSFVIRNGF GLVRTFNTRL FTTSTQNLEG ELKTILGQAK VSKLQEKLKL DPRSKITFND
FKGIAKEVGI EEKEINSVSN ALAQSGSIIY LPNSLNENLK TSVFTKPAHI YQSLEHILDI
ENKGVGLNKL IESKKSEINS LRQKIQPLEE KKQVIDRKAH RRATAIIWTG LGYCFAQAAI
LARLTWWDLS WDIIEPVSYF LTFGSVLIGY TYFTMTKTEF TYEALNHRLF SKRQDKLFKR
NNFPKEDYEN LVQAIDKKEK ELKELELATK YDHTH
