EMRE_MOUSE
ID EMRE_MOUSE Reviewed; 107 AA.
AC Q9DB10; Q58EA5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Essential MCU regulator, mitochondrial {ECO:0000250|UniProtKB:Q9H4I9};
DE AltName: Full=Single-pass membrane protein with aspartate-rich tail 1, mitochondrial {ECO:0000312|MGI:MGI:1916279};
DE Flags: Precursor;
GN Name=Smdt1 {ECO:0000312|MGI:MGI:1916279};
GN Synonyms=Emre {ECO:0000250|UniProtKB:Q9H4I9};
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, and NOD; TISSUE=Cerebellum;
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=C57BL/6J; TISSUE=Brain, and Mammary gland;
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 TISSUE SPECIFICITY.
RX PubMed=24231807; DOI=10.1126/science.1242993;
RA Sancak Y., Markhard A.L., Kitami T., Kovacs-Bogdan E., Kamer K.J.,
RA Udeshi N.D., Carr S.A., Chaudhuri D., Clapham D.E., Li A.A., Calvo S.E.,
RA Goldberger O., Mootha V.K.;
RT "EMRE is an essential component of the mitochondrial calcium uniporter
RT complex.";
RL Science 342:1379-1382(2013).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION WITH MCU, AND
RP MUTAGENESIS OF PRO-60 AND 85-SER--ALA-90.
RX PubMed=27001609; DOI=10.1016/j.bbabio.2016.03.019;
RA Yamamoto T., Yamagoshi R., Harada K., Kawano M., Minami N., Ido Y.,
RA Kuwahara K., Fujita A., Ozono M., Watanabe A., Yamada A., Terada H.,
RA Shinohara Y.;
RT "Analysis of the structure and function of EMRE in a yeast expression
RT system.";
RL Biochim. Biophys. Acta 1857:831-839(2016).
CC -!- FUNCTION: Essential regulatory subunit of the mitochondrial calcium
CC uniporter complex (uniplex), a complex that mediates calcium uptake
CC into mitochondria (PubMed:27001609). Required to bridge the calcium-
CC sensing proteins MICU1 and MICU2 with the calcium-conducting subunit
CC MCU. Plays a central role in regulating the uniplex complex response to
CC intracellular calcium signaling. Acts by mediating activation of MCU
CC and retention of MICU1 to the MCU pore, in order to ensure tight
CC regulation of the uniplex complex and appropriate responses to
CC intracellular calcium signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q9H4I9, ECO:0000269|PubMed:27001609}.
CC -!- SUBUNIT: Component of the uniplex complex, composed of MCU, MCUB,
CC MICU1, MICU2 and EMRE/SMDT1 (By similarity). Interacts (via the
CC transmembrane region) with MCU (via the first transmembrane region);
CC the interaction is direct (PubMed:27001609). Interacts (via the poly-
CC Asp region) with MICU1 (via polybasic region); the interaction is
CC direct (By similarity). Interacts (via its C-terminal poly-Asp tail)
CC with MCUR1; the interaction is direct (By similarity). Unprocessed form
CC interacts (via transit peptide) with MAIP1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9H4I9, ECO:0000269|PubMed:27001609}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:27001609}; Single-pass membrane protein
CC {ECO:0000269|PubMed:27001609}. Note=MAIP1 is required to assist sorting
CC of EMRE/SMDT1 into mitochondrion by protecting EMRE/SMDT1 against
CC protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation
CC by the mitochondrial processing peptidase (PMPCA and PMPCB).
CC {ECO:0000250|UniProtKB:Q9H4I9}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:24231807}.
CC -!- DOMAIN: The GXXXX[G/A/S] motif at the C-terminal part of the
CC transmembrane region mediates interaction with MCU and is required to
CC activate the calcium-conducting pore in the uniporter complex.
CC {ECO:0000250|UniProtKB:Q9H4I9}.
CC -!- DOMAIN: The poly-Asp region at the C-terminus mediates interaction with
CC the polybasic region of MICU1. {ECO:0000250|UniProtKB:Q9H4I9}.
CC -!- PTM: Undergoes proteolytic degradation in neurons: degraded by AFG3L2
CC before SMDT1/EMRE assembly with the uniporter complex, limiting the
CC availability of SMDT1/EMRE for MCU assembly and promoting efficient
CC assembly of gatekeeper subunits with MCU.
CC {ECO:0000250|UniProtKB:Q9H4I9}.
CC -!- SIMILARITY: Belongs to the SMDT1/EMRE family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH92006.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK005345; BAB23967.1; -; mRNA.
DR EMBL; AK170899; BAE42102.1; -; mRNA.
DR EMBL; BC028457; AAH28457.1; -; mRNA.
DR EMBL; BC092006; AAH92006.1; ALT_FRAME; mRNA.
DR CCDS; CCDS27688.1; -.
DR RefSeq; NP_081190.1; NM_026914.1.
DR AlphaFoldDB; Q9DB10; -.
DR SMR; Q9DB10; -.
DR STRING; 10090.ENSMUSP00000023086; -.
DR MaxQB; Q9DB10; -.
DR PaxDb; Q9DB10; -.
DR PeptideAtlas; Q9DB10; -.
DR PRIDE; Q9DB10; -.
DR ProteomicsDB; 275862; -.
DR Antibodypedia; 27229; 20 antibodies from 8 providers.
DR DNASU; 69029; -.
DR Ensembl; ENSMUST00000023086; ENSMUSP00000023086; ENSMUSG00000022452.
DR GeneID; 69029; -.
DR KEGG; mmu:69029; -.
DR UCSC; uc007wzb.1; mouse.
DR CTD; 91689; -.
DR MGI; MGI:1916279; Smdt1.
DR VEuPathDB; HostDB:ENSMUSG00000022452; -.
DR eggNOG; KOG4542; Eukaryota.
DR GeneTree; ENSGT00390000017489; -.
DR HOGENOM; CLU_172921_1_0_1; -.
DR InParanoid; Q9DB10; -.
DR OMA; FPNMAAR; -.
DR OrthoDB; 1586309at2759; -.
DR PhylomeDB; Q9DB10; -.
DR TreeFam; TF314649; -.
DR Reactome; R-MMU-8949215; Mitochondrial calcium ion transport.
DR Reactome; R-MMU-8949664; Processing of SMDT1.
DR BioGRID-ORCS; 69029; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Smdt1; mouse.
DR PRO; PR:Q9DB10; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9DB10; protein.
DR Bgee; ENSMUSG00000022452; Expressed in embryonic brain and 272 other tissues.
DR ExpressionAtlas; Q9DB10; baseline and differential.
DR Genevisible; Q9DB10; MM.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:1990246; C:uniplex complex; ISS:UniProtKB.
DR GO; GO:0036444; P:calcium import into the mitochondrion; 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 InterPro; IPR018782; MCU_reg.
DR PANTHER; PTHR33904; PTHR33904; 1.
DR Pfam; PF10161; DDDD; 1.
PE 1: Evidence at protein level;
KW Calcium; Calcium transport; Ion transport; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..47
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 48..107
FT /note="Essential MCU regulator, mitochondrial"
FT /id="PRO_0000296321"
FT TOPO_DOM 48..64
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:27001609"
FT TRANSMEM 65..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 85..107
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:27001609"
FT MOTIF 81..85
FT /note="GXXXX[G/A/S]"
FT /evidence="ECO:0000250|UniProtKB:Q9H4I9"
FT MUTAGEN 60
FT /note="P->A: Abolishes calcium uptake into mitochondria.
FT Abolishes interaction with MCU."
FT /evidence="ECO:0000269|PubMed:27001609"
FT MUTAGEN 85..90
FT /note="Missing: Abolishes calcium uptake into mitochondria.
FT Abolishes interaction with MCU."
FT /evidence="ECO:0000269|PubMed:27001609"
SQ SEQUENCE 107 AA; 11542 MW; 5D3A608DE54EE95E CRC64;
MASTAARRLA WVAVRPGALW SGPRGRRGGD VYTVPGSSGL SQVPSRSVIV TRSGAILPKP
VKMSFGLLRV FSIVIPFLYV GTLISKNFAA LLEEHDIFVP EDDDDDD
