LETM1_MOUSE
ID LETM1_MOUSE Reviewed; 738 AA.
AC Q9Z2I0; Q5PQC5; Q7TMK8; Q80ZX6; Q8CGJ3; Q8K5E5;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Mitochondrial proton/calcium exchanger protein {ECO:0000305};
DE AltName: Full=Leucine zipper-EF-hand-containing transmembrane protein 1;
DE Flags: Precursor;
GN Name=Letm1 {ECO:0000312|MGI:MGI:1932557};
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 [MRNA].
RX PubMed=10486213; DOI=10.1006/geno.1999.5881;
RA Endele S., Fuhry M., Pak S.-J., Zabel B.U., Winterpacht A.;
RT "LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein,
RT flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in
RT most WHS patients.";
RL Genomics 60:218-225(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, 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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-737.
RC STRAIN=C57BL/6J;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, AND MUTAGENESIS OF
RP ASP-204; GLU-221 AND 246-ASP-ASP-247.
RX PubMed=27669901; DOI=10.1038/srep34174;
RA Shao J., Fu Z., Ji Y., Guan X., Guo S., Ding Z., Yang X., Cong Y., Shen Y.;
RT "Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a
RT Ca(2+)/H(+) antiporter.";
RL Sci. Rep. 6:34174-34174(2016).
CC -!- FUNCTION: Mitochondrial proton/calcium antiporter that mediates proton-
CC dependent calcium efflux from mitochondrion (PubMed:27669901). Crucial
CC for the maintenance of mitochondrial tubular networks and for the
CC assembly of the supercomplexes of the respiratory chain (By
CC similarity). Required for the maintenance of the tubular shape and
CC cristae organization (By similarity). In contrast to SLC8B1/NCLX, does
CC not constitute the major factor for mitochondrial calcium extrusion (By
CC similarity). {ECO:0000250|UniProtKB:O95202,
CC ECO:0000269|PubMed:27669901}.
CC -!- ACTIVITY REGULATION: Inhibited by ruthenium red or its derivative
CC Ru360. {ECO:0000250|UniProtKB:O95202}.
CC -!- SUBUNIT: Homohexamer (PubMed:27669901). Interacts with BCS1L (By
CC similarity). {ECO:0000250|UniProtKB:O95202,
CC ECO:0000269|PubMed:27669901}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:27669901}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the LETM1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH23862.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH46326.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH55865.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF061026; AAD13139.1; -; mRNA.
DR EMBL; BC023862; AAH23862.1; ALT_SEQ; mRNA.
DR EMBL; BC046326; AAH46326.1; ALT_SEQ; mRNA.
DR EMBL; BC055865; AAH55865.1; ALT_SEQ; mRNA.
DR EMBL; BC061115; AAH61115.1; -; mRNA.
DR EMBL; AB041582; BAB93544.1; -; mRNA.
DR CCDS; CCDS19207.1; -.
DR RefSeq; NP_062668.1; NM_019694.1.
DR AlphaFoldDB; Q9Z2I0; -.
DR SMR; Q9Z2I0; -.
DR BioGRID; 207944; 9.
DR IntAct; Q9Z2I0; 3.
DR MINT; Q9Z2I0; -.
DR STRING; 10090.ENSMUSP00000005431; -.
DR iPTMnet; Q9Z2I0; -.
DR PhosphoSitePlus; Q9Z2I0; -.
DR SwissPalm; Q9Z2I0; -.
DR EPD; Q9Z2I0; -.
DR jPOST; Q9Z2I0; -.
DR MaxQB; Q9Z2I0; -.
DR PaxDb; Q9Z2I0; -.
DR PeptideAtlas; Q9Z2I0; -.
DR PRIDE; Q9Z2I0; -.
DR ProteomicsDB; 286186; -.
DR Antibodypedia; 2597; 266 antibodies from 30 providers.
DR DNASU; 56384; -.
DR Ensembl; ENSMUST00000005431; ENSMUSP00000005431; ENSMUSG00000005299.
DR GeneID; 56384; -.
DR KEGG; mmu:56384; -.
DR UCSC; uc008xbi.1; mouse.
DR CTD; 3954; -.
DR MGI; MGI:1932557; Letm1.
DR VEuPathDB; HostDB:ENSMUSG00000005299; -.
DR eggNOG; KOG1043; Eukaryota.
DR GeneTree; ENSGT00950000183167; -.
DR HOGENOM; CLU_008958_2_1_1; -.
DR InParanoid; Q9Z2I0; -.
DR OMA; EILHYYH; -.
DR OrthoDB; 516860at2759; -.
DR PhylomeDB; Q9Z2I0; -.
DR TreeFam; TF316321; -.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR BioGRID-ORCS; 56384; 24 hits in 73 CRISPR screens.
DR ChiTaRS; Letm1; mouse.
DR PRO; PR:Q9Z2I0; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9Z2I0; protein.
DR Bgee; ENSMUSG00000005299; Expressed in right kidney and 249 other tissues.
DR ExpressionAtlas; Q9Z2I0; baseline and differential.
DR Genevisible; Q9Z2I0; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0015369; F:calcium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043022; F:ribosome binding; IEA:InterPro.
DR GO; GO:0099093; P:calcium export from the mitochondrion; IDA:UniProtKB.
DR GO; GO:0006875; P:cellular metal ion homeostasis; IBA:GO_Central.
DR GO; GO:0042407; P:cristae formation; ISO:MGI.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:0006851; P:mitochondrial calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051562; P:negative regulation of mitochondrial calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA: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; IPR011685; LETM1-like.
DR InterPro; IPR044202; LETM1/MDM38-like.
DR InterPro; IPR033122; LETM1_RBD.
DR PANTHER; PTHR14009; PTHR14009; 1.
DR Pfam; PF07766; LETM1; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS51758; LETM1_RBD; 1.
PE 1: Evidence at protein level;
KW Acetylation; Antiport; Calcium; Calcium transport; Coiled coil;
KW Ion transport; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Transmembrane; Transmembrane helix; Transport.
FT TRANSIT 1..114
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 115..738
FT /note="Mitochondrial proton/calcium exchanger protein"
FT /id="PRO_0000017695"
FT TOPO_DOM 115..207
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:27669901"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..738
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:27669901"
FT DOMAIN 251..536
FT /note="Letm1 RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01094"
FT DOMAIN 662..697
FT /note="EF-hand"
FT REGION 719..738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 115..135
FT /evidence="ECO:0000255"
FT COILED 247..283
FT /evidence="ECO:0000255"
FT COILED 445..492
FT /evidence="ECO:0000255"
FT COILED 537..626
FT /evidence="ECO:0000255"
FT COILED 707..738
FT /evidence="ECO:0000255"
FT BINDING 675
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 677
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 679
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 681
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 686
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT MOD_RES 596
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O95202"
FT MUTAGEN 204
FT /note="D->N: Does not affect mitochondrial localization and
FT ability to mediate calcium efflux from mitochondrion."
FT /evidence="ECO:0000269|PubMed:27669901"
FT MUTAGEN 221
FT /note="E->Q: Does not affect mitochondrial localization but
FT abolishes ability to mediate calcium efflux from
FT mitochondrion."
FT /evidence="ECO:0000269|PubMed:27669901"
FT MUTAGEN 246..247
FT /note="EE->AA: Does not affect mitochondrial localization
FT and ability to mediate calcium efflux from mitochondrion."
FT /evidence="ECO:0000269|PubMed:27669901"
FT CONFLICT 271
FT /note="A -> P (in Ref. 2; AAH23862)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 738 AA; 82989 MW; 5074CE6309940729 CRC64;
MASILLRSCR GRGPARLAPP RAASPRGSLR DRACLSCTRT LGLTSRESVL SRCCTPAHPV
YLCFKGEPLS CWTQRPECQG TAARTTWTPA SARLVVTGPQ YLPVRGWHSS SPLGEDSVIE
KSLKSLKDKN KKLEEGGPVY SPPAQVVVRK SLGQKVLDEL RHYYHGFRLL WIDTKIAARM
LWRILNGHTL TRRERRQFLR ICADLFRLVP FLVFVVVPFM EFLLPVVVKL FPNMLPSTFE
TQSIKEERLK KELRVKLELA KFLQDTIEEM ALKNKAAKGN ATKDFSAFFQ KIRETGERPS
NEEIMRFSKL FEDELTLDNL TRPQLVALCK LLELQSIGTN NFLRFQLTMR LRSIKADDKL
ISEEGVDSLT VKELQAACRA RGMRALGVTE DRLKGQLKQW LDLHLHHEIP TSLLILSRAM
YLPDTLSPAD QLKSTLQTLP EIVAKEAQVK VAEVEGEKVD NKAKLEATLQ EEAAIQQEHL
EELKRASEAV KDIQPEVAEA TLPGRPGPEP QPPVDDVILP SEVLTDTAPV LEGLKGEEIT
KEEIDILSDA CSKLQEQKKS LTKEKEELEL LKEDVQDYSE DLQEIKKELS KTGEEKYIEE
SAASKRLSKR VQQMIGQIDG LITQLETTQQ DGKLGPSQST PTGESVISIT ELISAMKQIK
HIPEHKLISL TSALDDNKDG NINIDDLVKV IDLVNKEDVQ ISTTQVAEIV ATLEKEEKIE
EKEKAKEKAE KEAAEVKN
