MICU1_BOVIN
ID MICU1_BOVIN Reviewed; 478 AA.
AC Q0IIL1;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 101.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hippocampus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) 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. Regulates glucose-dependent insulin secretion in pancreatic
CC beta-cells by regulating mitochondrial calcium uptake. Induces T-helper
CC 1-mediated autoreactivity, which is accompanied by the release of IFNG.
CC {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, composed of MCU, MCUB, MICU1, MICU2 and
CC EMRE/SMDT1. Interacts (via polybasic region) with EMRE/SMDT1; the
CC interaction is direct. Interacts (via polybasic region) with MCU (via
CC coiled coil domains); the interaction is direct and precedes formation
CC of the heterodimer with MICU2. Interacts with SLC25A23. Interacts with
CC CHCHD4/MIA40; which introduces the interchain disulfide bond with
CC MICU2. {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}.
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DR EMBL; BC122590; AAI22591.1; -; mRNA.
DR RefSeq; NP_001068806.1; NM_001075338.1.
DR AlphaFoldDB; Q0IIL1; -.
DR SMR; Q0IIL1; -.
DR STRING; 9913.ENSBTAP00000007636; -.
DR PaxDb; Q0IIL1; -.
DR PRIDE; Q0IIL1; -.
DR Ensembl; ENSBTAT00000007636; ENSBTAP00000007636; ENSBTAG00000005807.
DR GeneID; 507899; -.
DR KEGG; bta:507899; -.
DR CTD; 10367; -.
DR VEuPathDB; HostDB:ENSBTAG00000005807; -.
DR VGNC; VGNC:31461; MICU1.
DR eggNOG; KOG2643; Eukaryota.
DR GeneTree; ENSGT00950000183079; -.
DR HOGENOM; CLU_027103_3_1_1; -.
DR InParanoid; Q0IIL1; -.
DR OMA; WKAEFRQ; -.
DR OrthoDB; 707988at2759; -.
DR TreeFam; TF313815; -.
DR Proteomes; UP000009136; Chromosome 28.
DR Bgee; ENSBTAG00000005807; Expressed in semitendinosus and 103 other tissues.
DR ExpressionAtlas; Q0IIL1; baseline and differential.
DR GO; GO:0034704; C:calcium channel complex; ISS:UniProtKB.
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:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB.
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 GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR GO; GO:1900069; P:regulation of cellular hyperosmotic salinity response; 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; 2.
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..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6, ECO:0000255"
FT CHAIN 34..478
FT /note="Calcium uptake protein 1, mitochondrial"
FT /id="PRO_0000322989"
FT TRANSMEM 34..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..478
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT DOMAIN 220..255
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 410..445
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 61..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..112
FT /note="Polybasic region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT REGION 457..467
FT /note="C-helix region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT COMPBIAS 70..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 239
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 423
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 425
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 427
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 429
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 434
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DISULFID 465
FT /note="Interchain (with C-413 in MICU2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
SQ SEQUENCE 478 AA; 54422 MW; DF8D37DBD2202DF9 CRC64;
MFRLNSLSAL AELAVGSRWY HGGSQPTQIR RRLMMVAFLG ASAVTASTGL LWKRALAESP
PSANNIKSEL GDKGKSKEEG EDCNAEKKAA GVCLEPYPEE KKKKRSGFRD RKVMEYENRI
RAYSTPDKIF RYFATLKVIS EHGESEVFMT PQDFVRSITP NEKQPEHLGL DQYTIKRFDG
KKIAQEREKF ADEGSIFYTL GECGLISFSD YIFLTTVLST PQRNFEIAFK MFDLNGDGEV
DMEEFEQVQS IIRSQTSMGM RHRDRSTTGN TLKSGLCSAL TTYFFGADLK GKLTIKNFLE
FQRKLQHDVL KLEFERHDPV DGRITERQFG GMLLAYSGVQ SKKLTAMQKQ LKKHFKEGKG
LTFQEVENFF TFLKNINDVD TALSFYHMAG ASLDKVTMQQ VARTVAKVEL SDHVCDVVFA
LFDCDGNGEL SNKEFVSIMK QRLMRGLEKP KDMGFTRLMQ AMWKCAQETA WDFALPKQ
