MCU_DANRE
ID MCU_DANRE Reviewed; 376 AA.
AC Q08BI9;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Calcium uniporter protein, mitochondrial;
DE Flags: Precursor;
GN Name=mcu; ORFNames=zgc:153607 {ECO:0000303|Ref.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Mitochondrial inner membrane calcium uniporter that mediates
CC calcium uptake into mitochondria. Constitutes the pore-forming and
CC calcium-conducting subunit of the uniporter complex (uniplex). Activity
CC is regulated by micu1 and micu2. At low Ca(2+) levels mcu activity is
CC down-regulated by micu1 and micu2; at higher Ca(2+) levels micu1
CC increases mcu activity. Mitochondrial calcium homeostasis plays key
CC roles in cellular physiology and regulates cell bioenergetics,
CC cytoplasmic calcium signals and activation of cell death pathways.
CC Involved in buffering the amplitude of systolic calcium rises in
CC cardiomyocytes. While dispensable for baseline homeostatic cardiac
CC function, acts as a key regulator of short-term mitochondrial calcium
CC loading underlying a 'fight-or-flight' response during acute stress:
CC acts by mediating a rapid increase of mitochondrial calcium in
CC pacemaker cells. {ECO:0000250|UniProtKB:Q3UMR5,
CC ECO:0000250|UniProtKB:Q8NE86}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative
CC Ru360. {ECO:0000250|UniProtKB:Q8NE86}.
CC -!- SUBUNIT: Component of the uniplex complex (By similarity).
CC Homooligomer; forms a pentamer (By similarity).
CC {ECO:0000250|UniProtKB:Q21121, ECO:0000250|UniProtKB:Q3UMR5,
CC ECO:0000250|UniProtKB:Q8NE86}.
CC -!- INTERACTION:
CC Q08BI9; Q08BI9: mcu; NbExp=2; IntAct=EBI-20717912, EBI-20717912;
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: 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 -!- 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:0000250|UniProtKB:Q8NE86}.
CC -!- SIMILARITY: Belongs to the MCU (TC 1.A.77) family. {ECO:0000305}.
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DR EMBL; BC124705; AAI24706.1; -; mRNA.
DR RefSeq; NP_001070793.1; NM_001077325.1.
DR AlphaFoldDB; Q08BI9; -.
DR SMR; Q08BI9; -.
DR STRING; 7955.ENSDARP00000108433; -.
DR PaxDb; Q08BI9; -.
DR GeneID; 768182; -.
DR KEGG; dre:768182; -.
DR CTD; 90550; -.
DR ZFIN; ZDB-GENE-061013-24; mcu.
DR eggNOG; KOG2966; Eukaryota.
DR InParanoid; Q08BI9; -.
DR OrthoDB; 1076768at2759; -.
DR PhylomeDB; Q08BI9; -.
DR Reactome; R-DRE-8949215; Mitochondrial calcium ion transport.
DR PRO; PR:Q08BI9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0034704; C:calcium channel complex; ISS:UniProtKB.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:1990246; C:uniplex complex; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0015292; F:uniporter activity; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IMP:ZFIN.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IDA:ZFIN.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0043009; P:chordate embryonic development; IMP:ZFIN.
DR GO; GO:0060027; P:convergent extension involved in gastrulation; IMP:ZFIN.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IMP:ZFIN.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; IGI:ZFIN.
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 Calcium; Calcium channel; Calcium transport; Coiled coil; Ion channel;
KW Ion transport; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transit peptide; Transmembrane; Transmembrane helix;
KW Transport.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 35..376
FT /note="Calcium uniporter protein, mitochondrial"
FT /id="PRO_0000282978"
FT TOPO_DOM 35..257
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 258..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..289
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT TRANSMEM 290..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..376
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT REGION 99..189
FT /note="N-terminal MCU domain"
FT /evidence="ECO:0000250|UniProtKB:Q8NE86"
FT REGION 240..258
FT /note="Outer juxtamembrane helix (OJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT REGION 307..316
FT /note="Inner juxtamembrane helix (IJMH)"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
FT COILED 213..254
FT /evidence="ECO:0000255"
FT COILED 336..363
FT /evidence="ECO:0000255"
FT MOTIF 285..288
FT /note="DXXE"
FT /evidence="ECO:0000250|UniProtKB:Q21121"
SQ SEQUENCE 376 AA; 42864 MW; EB9696F06AE12AC8 CRC64;
MAAKVCRSVL LLSRSSGAVA SSAYPAFGVS SQRHQGTKTE ALSMSLGGHQ TVRRAHGLRT
GGRCALFCHP SATLTAQGWK GSPSWQVQRL LCSPAAEDVS VVYQNGLPVI SVRLPSRRER
CQFTLKPLSD TVGVFLQQLQ AEDRGIDRVT IYSADGARIA SSTGIDILLM DNFKLVINDT
SYLVQPPRRD LLPHEDGERL NDVKILVQQL YTTLRIEEHQ LNKERELIGR LEDLNSQLQP
LEKVKEELSK KAERRTTWVL WGGMAYMATQ FGILARLTWW EYSWDIMEPV TYFITYGTAM
AMYAYFVLTR QEYLYPDARD RQYLLFFHRG AKRTRFDIEK YNKLKDAIAE AELDLKRLRD
PLQLNLPIQQ IDTSKD
