MICU1_DANRE
ID MICU1_DANRE Reviewed; 489 AA.
AC A4IG32; B8JIY1; B8JJM2;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Calcium uptake protein 1, mitochondrial;
DE AltName: Full=Calcium-binding atopy-related autoantigen 1 homolog;
DE Flags: Precursor;
GN Name=micu1; Synonyms=cbara1; ORFNames=si:ch211-199i24.4, zgc:162148;
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 GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) that
CC senses calcium level via its EF-hand domains. micu1 and micu2 form a
CC disulfide-linked heterodimer that stimulates and inhibits mcu activity,
CC depending on the concentration of calcium. Micu1 acts both as an
CC activator or inhibitor of mitochondrial calcium uptake. Acts as a
CC gatekeeper of mcu at low concentration of calcium, preventing channel
CC opening. Enhances mcu opening at high calcium concentration, allowing a
CC rapid response of mitochondria to calcium signals generated in the
CC cytoplasm. {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- SUBUNIT: Homohexamer; in absence of calcium. Forms a homohexamer in
CC absence of calcium and rearranges into a heterodimer in presence of
CC calcium. Heterodimer; disulfide-linked; heterodimerizes with MICU2. The
CC heterodimer formed with MICU2 associates with MCU at low calcium
CC concentration and dissociates from MCU at high calcium level. Component
CC of the uniplex complex. {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q9BPX6}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q9BPX6}. Note=The topology is subject to debate.
CC {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- DOMAIN: The C-helix is required for assembling the Ca(2+)-free
CC homohexamer. It also plays a key role in mitochondrial calcium uptake,
CC probably by mediating interaction with MICU2.
CC {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- DOMAIN: The EF-hand domains have high affinity for calcium and act as
CC sensors of calcium levels. {ECO:0000250|UniProtKB:Q9BPX6}.
CC -!- SIMILARITY: Belongs to the MICU1 family. MICU1 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAX13264.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CT025754; CAX13263.1; -; Genomic_DNA.
DR EMBL; CR854925; CAX13263.1; JOINED; Genomic_DNA.
DR EMBL; CR854925; CAX13564.1; -; Genomic_DNA.
DR EMBL; CT025754; CAX13564.1; JOINED; Genomic_DNA.
DR EMBL; CT025754; CAX13264.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC134905; AAI34906.1; -; mRNA.
DR RefSeq; NP_001077302.1; NM_001083833.1.
DR AlphaFoldDB; A4IG32; -.
DR SMR; A4IG32; -.
DR STRING; 7955.ENSDARP00000121050; -.
DR PaxDb; A4IG32; -.
DR PeptideAtlas; A4IG32; -.
DR PRIDE; A4IG32; -.
DR Ensembl; ENSDART00000132301; ENSDARP00000121050; ENSDARG00000063358.
DR GeneID; 561210; -.
DR KEGG; dre:561210; -.
DR CTD; 10367; -.
DR ZFIN; ZDB-GENE-070410-22; micu1.
DR eggNOG; KOG2643; Eukaryota.
DR GeneTree; ENSGT00950000183079; -.
DR HOGENOM; CLU_027103_3_1_1; -.
DR InParanoid; A4IG32; -.
DR OrthoDB; 707988at2759; -.
DR PhylomeDB; A4IG32; -.
DR TreeFam; TF313815; -.
DR Reactome; R-DRE-8949215; Mitochondrial calcium ion transport.
DR PRO; PR:A4IG32; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 13.
DR Bgee; ENSDARG00000063358; Expressed in pharyngeal gill and 22 other tissues.
DR ExpressionAtlas; A4IG32; baseline and differential.
DR GO; GO:0032592; C:integral component of mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:1990246; C:uniplex complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0036444; P:calcium import into the mitochondrion; IBA:GO_Central.
DR GO; GO:0070509; P:calcium ion import; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; ISS:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR039800; MICU1/2/3.
DR PANTHER; PTHR12294; PTHR12294; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 2: Evidence at transcript level;
KW Calcium; Calcium transport; Disulfide bond; Ion transport; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Repeat; Transit peptide; Transmembrane;
KW Transmembrane helix; Transport.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6, ECO:0000255"
FT CHAIN 35..489
FT /note="Calcium uptake protein 1, mitochondrial"
FT /id="PRO_0000322994"
FT TRANSMEM 35..53
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 54..489
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT DOMAIN 229..264
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 371..386
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 420..455
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 62..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 106..117
FT /note="Polybasic region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT REGION 467..477
FT /note="C-helix region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT COMPBIAS 62..84
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 253
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 435
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DISULFID 475
FT /note="Interchain (with C-413 in micu2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
SQ SEQUENCE 489 AA; 55925 MW; 03CA5CE8734CDD0F CRC64;
MYRLRALTAA TVGMVQLTRR HHTGAFRSYQ RRRLMLAALA GVTGISASAG LMWTRAYAEA
GSSVKHEEQM REEEPLKDVA EEAESDGALE SSSGEDEDEA GSEEKKKKQR IGFRDRKVME
YENRIRAYST PDKIFRYFAT LKIINEHGDA EVYMTPQDFV RSITPNEKQP ENLGLDQFMV
KRYDGKDFWQ KISQDREKFA DEDSIFYTLG ECGLISFSDY IFLTTVLSTP QRNFEIAFKM
FDLNGDGEVD LEEFEQVQSI IRSQTSMGMR HRDRSTTGNT LKTGGCSSAL TTYFFGADLK
GKLTISSFLE FQRKLQHDVL KLEFERNDPV DGRITEKQFG GMLLAYSGVQ SRKLKQMQKN
LKRMFKDAQG ITFEEVENFF TFLKNVNDVD TALSFYHMAG ASIDKATMKQ VARTVAKVEL
SDHVCDVVFA LFDCDGNGEL SNKEFIAIMK QRLMRGLEKP KDMGFTRLVR AMWKCAQDTA
WDFAMPKQQ
