MICU1_AILME
ID MICU1_AILME Reviewed; 481 AA.
AC D2HZB0;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 1.
DT 03-AUG-2022, entry version 55.
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=PANDA_018142;
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
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; GL193792; EFB17693.1; -; Genomic_DNA.
DR AlphaFoldDB; D2HZB0; -.
DR SMR; D2HZB0; -.
DR STRING; 9646.ENSAMEP00000018360; -.
DR eggNOG; KOG2643; Eukaryota.
DR InParanoid; D2HZB0; -.
DR Proteomes; UP000008912; Unassembled WGS sequence.
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 3: Inferred from homology;
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..481
FT /note="Calcium uptake protein 1, mitochondrial"
FT /id="PRO_0000399808"
FT TRANSMEM 34..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..481
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 413..448
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 58..82
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 460..470
FT /note="C-helix region"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
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 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 428
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 430
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 BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DISULFID 468
FT /note="Interchain (with C-413 in MICU2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BPX6"
SQ SEQUENCE 481 AA; 54644 MW; 3070921F7028E689 CRC64;
MFRLHSLSAL AELAVGSRCY HGGSQPTQMK RRLMMVAFLG ASAVTASTGL LWKRALAESP
PSVNNPKSEL GDKGKNKDEG EVCNHEKKAA DVCLEPHPEE KKKKRSGFRD RKVMEYENRI
RAYSTPDKIF RYFATLKVIN EPGESEVFMT PQDFVRSITP NEKQPEHLGL DQYTIKRFDG
KKIAQEREKF ADEGSIFYTL GECGLISFSD YIFLTTVLST PQRNFEIAFK MFDLNGDGEV
DMEEFEQASC PGNIIRSQTS MGMRHRDRPT TGNTLKSGLC SALTTYFFGA DLKGKLTIKN
FLEFQRKLQH DVLKLEFERH DPVDGKITER QFGGMLLAYS GVQSKKLTAM QKQLKKHFKE
GKGLTFQEVE NFFTFLKNIN DVDTALSFYH MAGASLDKVT MQQVARTVAK VELSDHVCDV
VFALFDCDGN GELSNKEFVS IMKQRLMRGL EKPKDMGFTR LMQAMWKCAQ ETAWDFALPK
Q
