MCU_CAEEL
ID MCU_CAEEL Reviewed; 333 AA.
AC Q21121;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Calcium uniporter protein, mitochondrial {ECO:0000305};
DE Short=cMCU {ECO:0000303|PubMed:27135929};
DE Flags: Precursor;
GN Name=mcu-1 {ECO:0000303|PubMed:25313960, ECO:0000312|WormBase:K02B2.3};
GN ORFNames=K02B2.3 {ECO:0000312|WormBase:K02B2.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25313960; DOI=10.1016/j.devcel.2014.08.002;
RA Xu S., Chisholm A.D.;
RT "C. elegans epidermal wounding induces a mitochondrial ROS burst that
RT promotes wound repair.";
RL Dev. Cell 31:48-60(2014).
RN [3] {ECO:0000312|PDB:5ID3}
RP STRUCTURE BY NMR OF 167-317 OF MUTANT ALA-238, ACTIVITY REGULATION,
RP SUBUNIT, DOMAIN, AND MUTAGENESIS OF SER-238.
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 [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=28662030; DOI=10.1371/journal.pbio.2002047;
RA Hoang H.D., Miller M.A.;
RT "Chemosensory and hyperoxia circuits in C. elegans males influence sperm
RT navigational capacity.";
RL PLoS Biol. 15:E2002047-E2002047(2017).
RN [5]
RP FUNCTION.
RX PubMed=31983639; DOI=10.1016/j.cub.2019.12.061;
RA Tang N.H., Kim K.W., Xu S., Blazie S.M., Yee B.A., Yeo G.W., Jin Y.,
RA Chisholm A.D.;
RT "The mRNA Decay Factor CAR-1/LSM14 Regulates Axon Regeneration via
RT Mitochondrial Calcium Dynamics.";
RL Curr. Biol. 30:865-876(2020).
CC -!- FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates
CC calcium uptake into mitochondria (PubMed:25313960, PubMed:31983639).
CC Constitutes a pore-forming and calcium-conducting subunit (By
CC similarity). Mitochondrial calcium homeostasis plays key roles in
CC cellular physiology and regulates cell bioenergetics, cytoplasmic
CC calcium signals and activation of cell death pathways (By similarity).
CC Required for rapid mitochondrial calcium uptake and mitochondrial
CC reactive oxygen species (mtROS) production after wounding
CC (PubMed:25313960). In addition, together with mitochondrial calcium
CC regulator micu-1, required for mitochondrial calcium uptake following
CC axon injury in PLM touch receptor neurons (PubMed:31983639).
CC {ECO:0000250|UniProtKB:Q8NE86, ECO:0000269|PubMed:25313960,
CC ECO:0000269|PubMed:31983639}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative
CC Ru360; possibly by obstructing the pore. {ECO:0000269|PubMed:27135929}.
CC -!- INTERACTION:
CC Q21121; Q21121: mcu-1; NbExp=7; IntAct=EBI-11465987, EBI-11465987;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q8NE86}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8NE86}.
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 (residues 293-316): while the
CC transmembrane regions pack into a five-helix bundle having a largely
CC polar pore across the membrane, the coiled-coil outside the membrane
CC forms a pentamer with a hydrophobic core, which may contribute to
CC stabilizing the transmembrane pore structure. The transmembrane pore is
CC wrapped by the first transmembrane region through contacts between the
CC first and the second transmembrane regions. The second transmembrane is
CC followed by the inner juxtamembrane region (IJMH) that orients at a
CC wide angle relative to the second transmembrane. The two core domains
CC are held together on the periphery by the outer juxtamembrane helix
CC (OJMH), which contains a kink around Glu-204 and interacts with the
CC IJMH. {ECO:0000269|PubMed:27135929}.
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, both acidic residues are in position to form two
CC carboxylate rings: the Asp-240 ring is solvent exposed, and the Glu-243
CC ring is located deeper, guarding the entrance of the second
CC transmembrane pore. In absence of emre-1 regulator, the calcium ions
CC cannot exit the channel, suggesting that emre-1-binding induces
CC conformational rearrangements to allow calcium to exit.
CC {ECO:0000269|PubMed:27135929}.
CC -!- DISRUPTION PHENOTYPE: Null mutants are viable and fertile, but have
CC strongly impaired mitochondrial calcium uptake following laser or
CC needle wounding (PubMed:25313960). Reduces the wound-induced transient
CC elevations in mitochondrial reactive oxygen species superoxide (which
CC are known as mitochondrial flashes or mitoflashes) (PubMed:25313960).
CC Double knockout with the srb-13 xm1 mutant suppresses the sperm
CC navigation defect in the srb-13 single mutant (PubMed:28662030).
CC {ECO:0000269|PubMed:25313960, ECO:0000269|PubMed:28662030}.
CC -!- SIMILARITY: Belongs to the MCU (TC 1.A.77) family. {ECO:0000305}.
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DR EMBL; BX284604; CCD61802.1; -; Genomic_DNA.
DR PIR; B88700; B88700.
DR RefSeq; NP_500892.1; NM_068491.4.
DR PDB; 5ID3; NMR; -; A/B/C/D/E=167-318.
DR PDBsum; 5ID3; -.
DR AlphaFoldDB; Q21121; -.
DR BMRB; Q21121; -.
DR SMR; Q21121; -.
DR DIP; DIP-61976N; -.
DR IntAct; Q21121; 1.
DR STRING; 6239.K02B2.3; -.
DR EPD; Q21121; -.
DR PaxDb; Q21121; -.
DR PeptideAtlas; Q21121; -.
DR EnsemblMetazoa; K02B2.3.1; K02B2.3.1; WBGene00019296.
DR GeneID; 177362; -.
DR KEGG; cel:CELE_K02B2.3; -.
DR UCSC; K02B2.3.1; c. elegans.
DR CTD; 177362; -.
DR WormBase; K02B2.3; CE27192; WBGene00019296; mcu-1.
DR eggNOG; KOG2966; Eukaryota.
DR GeneTree; ENSGT00940000168365; -.
DR HOGENOM; CLU_056554_0_1_1; -.
DR InParanoid; Q21121; -.
DR OMA; DDIYVEY; -.
DR OrthoDB; 1076768at2759; -.
DR PhylomeDB; Q21121; -.
DR Reactome; R-CEL-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-CEL-8949664; Processing of SMDT1.
DR SignaLink; Q21121; -.
DR PRO; PR:Q21121; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00019296; Expressed in adult organism and 4 other tissues.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:1990246; C:uniplex complex; IBA:GO_Central.
DR GO; GO:0005262; F:calcium channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0015292; F:uniporter activity; IBA:GO_Central.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IMP:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:0061041; P:regulation of wound healing; IMP:UniProtKB.
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..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..333
FT /note="Calcium uniporter protein, mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000437212"
FT TOPO_DOM 23..214
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 215..234
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27135929"
FT TOPO_DOM 235..243
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 244..260
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27135929"
FT TOPO_DOM 261..333
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT REGION 195..213
FT /note="Outer juxtamembrane helix (OJMH)"
FT /evidence="ECO:0000269|PubMed:27135929"
FT REGION 262..271
FT /note="Inner juxtamembrane helix (IJMH)"
FT /evidence="ECO:0000269|PubMed:27135929"
FT COILED 180..193
FT /evidence="ECO:0000269|PubMed:27135929"
FT COILED 289..316
FT /evidence="ECO:0000269|PubMed:27135929"
FT MOTIF 240..243
FT /note="DXXE"
FT /evidence="ECO:0000269|PubMed:27135929"
FT MUTAGEN 238
FT /note="S->A: Strongly reduced sensitivity to ruthenium red
FT inhibition."
FT /evidence="ECO:0000269|PubMed:27135929"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 180..192
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 195..202
FT /evidence="ECO:0007829|PDB:5ID3"
FT TURN 203..206
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:5ID3"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 218..225
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 227..233
FT /evidence="ECO:0007829|PDB:5ID3"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 244..265
FT /evidence="ECO:0007829|PDB:5ID3"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:5ID3"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:5ID3"
FT HELIX 293..314
FT /evidence="ECO:0007829|PDB:5ID3"
SQ SEQUENCE 333 AA; 38554 MW; 14398F25E6C4D4EE CRC64;
MRNGRCLVTP FVTAQRLANL RNTLWNRQQI AFSTTTASSS TSPIQESSSP LSIRFEYGLP
LLDVPLPSRN EPCQFTMRPL SDTIGSLCEF LRQEDRGIDY VAVYGTNGVK LATCTSIEHL
LQFGSFRLRL NDKFFDVTVP KTGTMPYDSD KLRQLDDLRA TVASLHAALC VDEYKLSREK
KLLLQLENAE TLLAPLHDAK RKIEQECEAH TDRVMWAGFA AMGVQTGLFA RLTWWEYSWD
IMEPVTYFAT YSTVCATFGY YLYTQQSFEY PSARERVYTK QFYRRAQKQN FDIEKYNRLV
TEVDELRNQL KRMRDPLFQH LPVSYLSNLE AEK
