MICU2_RAT
ID MICU2_RAT Reviewed; 432 AA.
AC Q99P63;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=Calcium uptake protein 2, mitochondrial;
DE AltName: Full=EF-hand domain-containing family member A1;
DE Flags: Precursor;
GN Name=Micu2; Synonyms=Efha1, Smhs2; ORFNames=09C01;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Skeletal muscle;
RX PubMed=11596118; DOI=10.1002/jcb.1248;
RA Cros N., Tkatchenko A.V., Pisani D.F., Leclerc L., Leger J.J.,
RA Marini J.-F., Dechesne C.A.;
RT "Analysis of altered gene expression in rat soleus muscle atrophied by
RT disuse.";
RL J. Cell. Biochem. 83:508-519(2001).
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU)
CC required to limit calcium uptake by MCU when cytoplasmic calcium is
CC low. MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate
CC and inhibit MCU activity, depending on the concentration of calcium.
CC MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-
CC hand domains: prevents channel opening at resting calcium, avoiding
CC energy dissipation and cell-death triggering.
CC {ECO:0000250|UniProtKB:Q8IYU8}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked; heterodimerizes with MICU1.
CC Interacts with MCU. The heterodimer formed with MICU1 associates with
CC MCU at low calcium concentration and dissociates from MCU at high
CC calcium level. Component of the uniplex complex, composed of MCU, MCUB,
CC MICU1, MICU2 and EMRE/SMDT1. {ECO:0000250|UniProtKB:Q8IYU8}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:Q8IYU8}.
CC -!- DOMAIN: The EF-hand domains have high affinity for calcium and act as
CC sensors of mitochondrial matrix calcium levels. It is unclear which EF-
CC hand binds calcium as none of the 4 EF-hand domains seem to contain a
CC canonical calcium-binding site. {ECO:0000250|UniProtKB:Q8IYU8}.
CC -!- SIMILARITY: Belongs to the MICU1 family. MICU2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF327513; AAG53983.1; -; mRNA.
DR RefSeq; NP_599223.2; NM_134396.2.
DR AlphaFoldDB; Q99P63; -.
DR SMR; Q99P63; -.
DR STRING; 10116.ENSRNOP00000015233; -.
DR iPTMnet; Q99P63; -.
DR PhosphoSitePlus; Q99P63; -.
DR GeneID; 171433; -.
DR KEGG; rno:171433; -.
DR UCSC; RGD:619739; rat.
DR CTD; 221154; -.
DR RGD; 619739; Micu2.
DR eggNOG; KOG2643; Eukaryota.
DR InParanoid; Q99P63; -.
DR OrthoDB; 707988at2759; -.
DR PhylomeDB; Q99P63; -.
DR Reactome; R-RNO-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-RNO-8949664; Processing of SMDT1.
DR PRO; PR:Q99P63; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0034704; C:calcium channel complex; 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:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:1990246; C:uniplex complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISO:RGD.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051562; P:negative regulation of mitochondrial calcium ion concentration; 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; IPR002048; EF_hand_dom.
DR InterPro; IPR039800; MICU1/2/3.
DR PANTHER; PTHR12294; PTHR12294; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
PE 2: Evidence at transcript level;
KW Disulfide bond; Mitochondrion; Phosphoprotein; Reference proteome; Repeat;
KW Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..432
FT /note="Calcium uptake protein 2, mitochondrial"
FT /id="PRO_0000251219"
FT DOMAIN 169..204
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 224..259
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 290..325
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 359..394
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IYU8"
FT DISULFID 410
FT /note="Interchain (with C-465 in MICU1)"
FT /evidence="ECO:0000250|UniProtKB:Q8CD10"
SQ SEQUENCE 432 AA; 49442 MW; AC97748435027AA8 CRC64;
MAAAAGRSAW LAAWGGRLRR GLAAGRRAVP TRGPLAAAVA GVALAGAGAA WHHGRVKAAA
REGSRTVSAQ KNYLGPIEKL SLRKQRFMQF SSLEHDGEYY MTPRDFLFSV MFEQVERKTL
VKKLAKKDIE DVLSGIQTAR CGSTFFRDLG DKGVISYTEY LFLLTILTKP HSGFHVAFKM
LDVDGNEMIE RKEFVRLQKI ISKQDGFKTV KTNETEYQDP TVKEPGVNTT LQVRFFGKRG
EKKLHYKEFR RFVENLQTEV QEMEFLQFSK GLNFMRKEDF AEWLLFFTNT ENKDIYWRNV
REKLSVGESI SLDEFKSFCH FTTHLEDFAI AMQTFSLAHR PVRLAEFKRA VKVATGQELS
DNLLDTVFKI FDLDGDECLS HGEFLGVLKN RMHRGLWVSQ QQSVQEYWKC VKKESIKGVK
EAWRQQAGKG PF
