MICU2_MOUSE
ID MICU2_MOUSE Reviewed; 432 AA.
AC Q8CD10; Q3TJU4; Q8K0K2; Q9CUR8;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 136.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, Placenta, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH MCU AND MICU1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23409044; DOI=10.1371/journal.pone.0055785;
RA Plovanich M., Bogorad R.L., Sancak Y., Kamer K.J., Strittmatter L.,
RA Li A.A., Girgis H.S., Kuchimanchi S., De Groot J., Speciner L., Taneja N.,
RA Oshea J., Koteliansky V., Mootha V.K.;
RT "MICU2, a paralog of MICU1, resides within the mitochondrial uniporter
RT complex to regulate calcium handling.";
RL PLoS ONE 8:E55785-E55785(2013).
RN [5]
RP FUNCTION, CALCIUM-BINDING, INTERACTION WITH MICU1, AND MUTAGENESIS OF
RP ASP-372 AND CYS-410.
RX PubMed=24560927; DOI=10.1016/j.molcel.2014.01.013;
RA Patron M., Checchetto V., Raffaello A., Teardo E., Vecellio Reane D.,
RA Mantoan M., Granatiero V., Szabo I., De Stefani D., Rizzuto R.;
RT "MICU1 and MICU2 finely tune the mitochondrial Ca(2+) uniporter by exerting
RT opposite effects on MCU activity.";
RL Mol. Cell 53:726-737(2014).
CC -!- FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU)
CC required to limit calcium uptake by MCU when cytoplasmic calcium is low
CC (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-
CC linked heterodimer that stimulate and inhibit MCU activity, depending
CC on the concentration of calcium (PubMed:24560927). MICU2 acts as a
CC gatekeeper of MCU that senses calcium level via its EF-hand domains:
CC prevents channel opening at resting Ca(2+), avoiding energy dissipation
CC and cell-death triggering (PubMed:24560927).
CC {ECO:0000269|PubMed:23409044, ECO:0000269|PubMed:24560927}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked; heterodimerizes with MICU1
CC (PubMed:23409044, PubMed:24560927). Interacts with MCU
CC (PubMed:23409044). The heterodimer formed with MICU1 associates with
CC MCU at low calcium concentration and dissociates from MCU at high
CC calcium level (By similarity). Component of the uniplex complex,
CC composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1.
CC {ECO:0000250|UniProtKB:Q8IYU8, ECO:0000269|PubMed:23409044,
CC ECO:0000269|PubMed:24560927}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:23409044}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in stomach, intestine,
CC skeletal muscle, kidney, heart, testis, prostate and uterus.
CC {ECO:0000269|PubMed:23409044}.
CC -!- DOMAIN: The EF-hand domains have high affinity for calcium and act as
CC sensors of mitochondrial matrix calcium levels (PubMed:24560927). It is
CC unclear which EF-hand binds calcium as none of the 4 EF-hand domains
CC seem to contain a canonical calcium-binding site.
CC {ECO:0000269|PubMed:24560927}.
CC -!- SIMILARITY: Belongs to the MICU1 family. MICU2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AK014778; BAB29548.1; -; mRNA.
DR EMBL; AK031692; BAC27516.1; -; mRNA.
DR EMBL; AK167296; BAE39401.1; -; mRNA.
DR EMBL; BC031172; AAH31172.1; -; mRNA.
DR CCDS; CCDS27163.1; -.
DR RefSeq; NP_082919.1; NM_028643.3.
DR PDB; 6EAZ; X-ray; 2.50 A; A/B=68-432.
DR PDBsum; 6EAZ; -.
DR AlphaFoldDB; Q8CD10; -.
DR SMR; Q8CD10; -.
DR BioGRID; 212898; 1.
DR STRING; 10090.ENSMUSP00000022543; -.
DR iPTMnet; Q8CD10; -.
DR PhosphoSitePlus; Q8CD10; -.
DR EPD; Q8CD10; -.
DR MaxQB; Q8CD10; -.
DR PaxDb; Q8CD10; -.
DR PeptideAtlas; Q8CD10; -.
DR PRIDE; Q8CD10; -.
DR ProteomicsDB; 292323; -.
DR Antibodypedia; 22397; 125 antibodies from 19 providers.
DR DNASU; 68514; -.
DR Ensembl; ENSMUST00000022543; ENSMUSP00000022543; ENSMUSG00000021973.
DR GeneID; 68514; -.
DR KEGG; mmu:68514; -.
DR UCSC; uc007udv.1; mouse.
DR CTD; 221154; -.
DR MGI; MGI:1915764; Micu2.
DR VEuPathDB; HostDB:ENSMUSG00000021973; -.
DR eggNOG; KOG2643; Eukaryota.
DR GeneTree; ENSGT00950000183079; -.
DR HOGENOM; CLU_027103_0_1_1; -.
DR InParanoid; Q8CD10; -.
DR OMA; NETECQE; -.
DR OrthoDB; 707988at2759; -.
DR PhylomeDB; Q8CD10; -.
DR TreeFam; TF320374; -.
DR Reactome; R-MMU-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 68514; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Micu2; mouse.
DR PRO; PR:Q8CD10; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8CD10; protein.
DR Bgee; ENSMUSG00000021973; Expressed in manus and 227 other tissues.
DR Genevisible; Q8CD10; MM.
DR GO; GO:0034704; C:calcium channel complex; IDA: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; IMP:UniProtKB.
DR GO; GO:1990246; C:uniplex complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISO:MGI.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IMP: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; IMP: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 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Mitochondrion; Phosphoprotein;
KW Reference proteome; Repeat; 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_0000251218"
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:0000269|PubMed:24560927"
FT MUTAGEN 372
FT /note="D->A: Strong reduction of mitochondrial Ca(2+)
FT peaks."
FT /evidence="ECO:0000269|PubMed:24560927"
FT MUTAGEN 410
FT /note="C->A: Abolishes interaction with MICU2."
FT /evidence="ECO:0000269|PubMed:24560927"
FT CONFLICT 14
FT /note="W -> G (in Ref. 1; BAE39401)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="E -> K (in Ref. 1; BAC27516)"
FT /evidence="ECO:0000305"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 103..111
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 126..132
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 145..149
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 157..168
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 175..181
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 194..201
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 230..236
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 246..268
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 277..284
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 293..304
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 312..323
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 325..336
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 344..355
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 361..370
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 381..393
FT /evidence="ECO:0007829|PDB:6EAZ"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:6EAZ"
FT HELIX 403..422
FT /evidence="ECO:0007829|PDB:6EAZ"
FT TURN 423..425
FT /evidence="ECO:0007829|PDB:6EAZ"
SQ SEQUENCE 432 AA; 49476 MW; C2CCA2B6B241852D CRC64;
MAAAAGRSAW LAAWGGRLRR GLAAGRRAVP TRGPLAAAVA GVALAGAGAA WHHGRVKAAA
REGSRTVSAQ KNYLGPIEKL SLRKQRFMQF SSLEHDGEYY MTPRDFLFSV MFEQVERKTL
VKKLAKKDIE DVLSGIQTAR CGSTFFRDLG DKGVISYTEY LFLLTILTKP HSGFHVAFKM
LDVDGNEMIE RKEFVKLQKI ISKQDGFKTV KTNETEYQDP TVKEPGVNTT LQVRFFGKRG
EKKLHYKEFR RFMENLQTEV QEMEFLQFSK GLNFMRKEDF AEWLLFFTNT ENKDIYWRNV
REKLSVGESI SLDEFKSFCH FTTHLEDFAI AMQMFSLAHR PVRLAEFKRA VKVATGQELS
DNLLDTVFKI FDLDGDECLS HGEFLGVLKN RMHRGLWVSQ QQSVQEYWKC VKKESIKGVK
EAWRQQAGKG PF
