Calcium uptake protein 1, mitochondrial

UniProt data

UniProt name: MICU1_HUMAN (Q9BPX6)

Gene name: MICU1; Synonyms=CALC {ECO:0000303|PubMed:16002733}, CBARA1

Organism: Homo sapiens (Human).

Function: Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains (PubMed:20693986, PubMed:23101630, PubMed:23747253, PubMed:24313810, PubMed:24332854, PubMed:24503055, PubMed:24560927, PubMed:26341627, PubMed:26903221, PubMed:27099988). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium. MICU1 acts both as an activator or inhibitor of mitochondrial calcium uptake (PubMed:26903221). Acts as a gatekeeper of MCU at low concentration of calcium, preventing channel opening (PubMed:26903221). Enhances MCU opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm (PubMed:24560927, PubMed:26903221). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (PubMed:22904319). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (PubMed:16002733). {ECO:0000269|PubMed:16002733, ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:22904319, ECO:0000269|PubMed:23101630, ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24313810, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26341627, ECO:0000269|PubMed:26903221, ECO:0000269|PubMed:27099988}.

Subcellular location: Mitochondrion inner membrane {ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26774479, ECO:0000269|PubMed:27099988, ECO:0000305|PubMed:24231807}; Single- pass membrane protein {ECO:0000255}. Mitochondrion intermembrane space {ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26387864}. Note=The topology is subject to discussion. According to some reports, localizes at the outer surface of the mitochondrion inner membrane (PubMed:20693986, PubMed:24332854). According to another publication, forms a intramembrane hairpin loop without crossing the membrane (PubMed:23747253). Recent studies rather suggest that it contains a transmembrane region that crosses the mitochondrial inner membrane, with the main part of the protein localized in the mitochondrial intermembrane space (PubMed:26387864, PubMed:26489515). {ECO:0000269|PubMed:20693986, ECO:0000269|PubMed:23747253, ECO:0000269|PubMed:24332854, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26489515}.

Transmembrane domains:

  1. 34-52, 19 AA, Helical. {ECO:0000255}.

Sequence: 476 AA

10 20 30 40 50 60 MFRLNSLSAL AELAVGSRWY HGGSQPIQIR RRLMMVAFLG ASAVTASTGL LWKRAHAESP 70 80 90 100 110 120 PCVDNLKSDI GDKGKNKDEG DVCNHEKKTA DLAPHPEEKK KKRSGFRDRK VMEYENRIRA 130 140 150 160 170 180 YSTPDKIFRY FATLKVISEP GEAEVFMTPE DFVRSITPNE KQPEHLGLDQ YIIKRFDGKK 190 200 210 220 230 240 ISQEREKFAD EGSIFYTLGE CGLISFSDYI FLTTVLSTPQ RNFEIAFKMF DLNGDGEVDM 250 260 270 280 290 300 EEFEQVQSII RSQTSMGMRH RDRPTTGNTL KSGLCSALTT YFFGADLKGK LTIKNFLEFQ 310 320 330 340 350 360 RKLQHDVLKL EFERHDPVDG RITERQFGGM LLAYSGVQSK KLTAMQRQLK KHFKEGKGLT 370 380 390 400 410 420 FQEVENFFTF LKNINDVDTA LSFYHMAGAS LDKVTMQQVA RTVAKVELSD HVCDVVFALF 430 440 450 460 470 DCDGNGELSN KEFVSIMKQR LMRGLEKPKD MGFTRLMQAM WKCAQETAWD FALPKQ

CATM prediction

The sequence of MICU1_HUMAN returned 1 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
  30        40        50    
|    +    |    +    |    +		 (Å) (°) (Å) (°)  
Model 1 RRRLMMVAFLGASAVTASTGLLWKRA 7.4 -46.3° 3.6 36.9 -10.5

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


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Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 46, ALA, HA A, 45, THR, O 3.45Å
B, 49, GLY, HA1 A, 46, ALA, O 3.47Å
A, 42, SER, HA B, 45, THR, OG1 3.46Å
A, 46, ALA, HA B, 45, THR, O 3.45Å
A, 49, GLY, HA1 B, 46, ALA, O 3.47Å