MICU1_MACFA
ID MICU1_MACFA Reviewed; 476 AA.
AC Q4R518;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 81.
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=QflA-11816;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Frontal cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE01807.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB169726; BAE01807.1; ALT_FRAME; mRNA.
DR AlphaFoldDB; Q4R518; -.
DR SMR; Q4R518; -.
DR Proteomes; UP000233100; Unplaced.
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: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: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..476
FT /note="Calcium uptake protein 1, mitochondrial"
FT /id="PRO_0000322991"
FT TRANSMEM 34..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..476
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT DOMAIN 218..253
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 408..443
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 68..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..110
FT /note="Polybasic region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT REGION 455..465
FT /note="C-helix region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 421
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DISULFID 463
FT /note="Interchain (with C-413 in MICU2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
SQ SEQUENCE 476 AA; 54378 MW; F8BAFCF5CD8947D7 CRC64;
MFRLNSLSAL AELAVGSRWY HGGSQPIQIR RRLMMVAFLG ASAVTASTGL LWKRAHAESP
PCVDNLKSDI GDKGKNKDEG DVCNHEKKTA DLAPHPEEKK KKRSGFRDRK VMEYENRIRA
YSTPDKIFRY FATLKVINEP GEAEVFMTPE DFVRSITPNE KQPEHLGLDQ YIIKRFDGKK
ISQEREKFAD EGSIFYTLGE CGLISFSDYI FLTTVLSTPQ RNFEIAFKMF DLNGDGEVDM
EEFEQVQSII RSQTSMGMRH RDRPTTGNTL KSGLCSALTT YFFGADLKGK LTIKNFLEFQ
RKLQHDVLKL EFERHDPVDG RITERQFGGM LLAYSGVQSK KLTAMQRQLK KHFKEGKGLT
FQEVENFFTF LKNINDVDTA LSFYHMAGAS LDKVTMQQVA RTVAKVELSD HVCDVVFALF
DCDGNGELSN KEFVSIMKQR LMRGLEKPKD MGFTRLMQAM WKCAQETAWD FALPKQ
