LOCUS       NM_019694               5188 bp    mRNA    linear   ROD 09-FEB-2025
DEFINITION  Mus musculus leucine zipper-EF-hand containing transmembrane
            protein 1 (Letm1), mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_019694
VERSION     NM_019694.2
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 5188)
  AUTHORS   Zhang,D., Deng,W., Jiang,T., Zhao,Y., Bai,D., Tian,Y., Kong,S.,
            Zhang,L., Wang,H., Gao,S. and Lu,Z.
  TITLE     Maternal Ezh1/2 deficiency impairs the function of mitochondria in
            mouse oocytes and early embryos
  JOURNAL   J Cell Physiol 239 (6), e31244 (2024)
   PUBMED   38529784
REFERENCE   2  (bases 1 to 5188)
  AUTHORS   Meng,T.G., Guo,J.N., Zhu,L., Yin,Y., Wang,F., Han,Z.M., Lei,L.,
            Ma,X.S., Xue,Y., Yue,W., Nie,X.Q., Zhao,Z.H., Zhang,H.Y., Sun,S.M.,
            Ouyang,Y.C., Hou,Y., Schatten,H., Ju,Z., Ou,X.H., Wang,Z.B.,
            Wong,C.C.L., Li,Z. and Sun,Q.Y.
  TITLE     NLRP14 Safeguards Calcium Homeostasis via Regulating the K27
            Ubiquitination of Nclx in Oocyte-to-Embryo Transition
  JOURNAL   Adv Sci (Weinh) 10 (27), e2301940 (2023)
   PUBMED   37493331
REFERENCE   3  (bases 1 to 5188)
  AUTHORS   Chern,T., Achilleos,A., Tong,X., Hill,M.C., Saltzman,A.B.,
            Reineke,L.C., Chaudhury,A., Dasgupta,S.K., Redhead,Y., Watkins,D.,
            Neilson,J.R., Thiagarajan,P., Green,J.B.A., Malovannaya,A.,
            Martin,J.F., Rosenblatt,D.S. and Poche,R.A.
  TITLE     Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin
            metabolism and ribosomopathy
  JOURNAL   Nat Commun 13 (1), 134 (2022)
   PUBMED   35013307
  REMARK    Publication Status: Online-Only
REFERENCE   4  (bases 1 to 5188)
  AUTHORS   Huang,E., Qu,D., Huang,T., Rizzi,N., Boonying,W., Krolak,D.,
            Ciana,P., Woulfe,J., Klein,C., Slack,R.S., Figeys,D. and Park,D.S.
  TITLE     PINK1-mediated phosphorylation of LETM1 regulates mitochondrial
            calcium transport and protects neurons against mitochondrial stress
  JOURNAL   Nat Commun 8 (1), 1399 (2017)
   PUBMED   29123128
  REMARK    GeneRIF: This paper's findings delineate a mechanism by which PINK1
            regulates mitochondrial Ca(2+) level through LETM1 and suggest a
            model by which PINK1 loss leads to deficient phosphorylation of
            LETM1 and impaired mitochondrial Ca(2+) transport.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 5188)
  AUTHORS   Shao,J., Fu,Z., Ji,Y., Guan,X., Guo,S., Ding,Z., Yang,X., Cong,Y.
            and Shen,Y.
  TITLE     Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1)
            forms a Ca2+/H+ antiporter
  JOURNAL   Sci Rep 6, 34174 (2016)
   PUBMED   27669901
  REMARK    Publication Status: Online-Only
REFERENCE   6  (bases 1 to 5188)
  AUTHORS   Doonan,P.J., Chandramoorthy,H.C., Hoffman,N.E., Zhang,X.,
            Cardenas,C., Shanmughapriya,S., Rajan,S., Vallem,S., Chen,X.,
            Foskett,J.K., Cheung,J.Y., Houser,S.R. and Madesh,M.
  TITLE     LETM1-dependent mitochondrial Ca2+ flux modulates cellular
            bioenergetics and proliferation
  JOURNAL   FASEB J 28 (11), 4936-4949 (2014)
   PUBMED   25077561
  REMARK    GeneRIF: Reconstitution of LETM1 or antioxidant overexpression
            rescued mitochondrial Ca(2+) transport and bioenergetics
            Erratum:[FASEB J. 2015 Aug;29(8):3593. doi:
            10.1096/fj.14-256453ERR.. PMID: 26232296]
REFERENCE   7  (bases 1 to 5188)
  AUTHORS   Jiang,D., Zhao,L., Clish,C.B. and Clapham,D.E.
  TITLE     Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for
            normal glucose metabolism and alters brain function in
            Wolf-Hirschhorn syndrome
  JOURNAL   Proc Natl Acad Sci U S A 110 (24), E2249-E2254 (2013)
   PUBMED   23716663
  REMARK    GeneRIF: Data indicate that cellular Letm1 knockdown reduced
            Ca(2+)mito uptake, H(+)mito extrusion and impaired mitochondrial
            ATP generation capacity.
REFERENCE   8  (bases 1 to 5188)
  AUTHORS   Kuum,M., Veksler,V., Liiv,J., Ventura-Clapier,R. and Kaasik,A.
  TITLE     Endoplasmic reticulum potassium-hydrogen exchanger and small
            conductance calcium-activated potassium channel activities are
            essential for ER calcium uptake in neurons and cardiomyocytes
  JOURNAL   J Cell Sci 125 (Pt 3), 625-633 (2012)
   PUBMED   22331352
REFERENCE   9  (bases 1 to 5188)
  AUTHORS   Naf,D., Wilson,L.A., Bergstrom,R.A., Smith,R.S., Goodwin,N.C.,
            Verkerk,A., van Ommen,G.J., Ackerman,S.L., Frankel,W.N. and
            Schimenti,J.C.
  TITLE     Mouse models for the Wolf-Hirschhorn deletion syndrome
  JOURNAL   Hum Mol Genet 10 (2), 91-98 (2001)
   PUBMED   11152656
REFERENCE   10 (bases 1 to 5188)
  AUTHORS   Endele,S., Fuhry,M., Pak,S.J., Zabel,B.U. and Winterpacht,A.
  TITLE     LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding
            protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region
            and is deleted in most WHS patients
  JOURNAL   Genomics 60 (2), 218-225 (1999)
   PUBMED   10486213
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BY110340.1, AF061026.1, BQ178952.1, AK163499.1 and BY243359.1.
            
            On May 17, 2018 this sequence version replaced NM_019694.1.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC061115.1, BC061690.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN01164138, SAMN01164142
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-13                BY110340.1         2-14
            14-3493             AF061026.1         1-3480
            3494-3561           BQ178952.1         193-260
            3562-5145           AK163499.1         912-2495
            5146-5188           BY243359.1         372-414
FEATURES             Location/Qualifiers
     source          1..5188
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="5"
                     /map="5 17.83 cM"
     gene            1..5188
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /note="leucine zipper-EF-hand containing transmembrane
                     protein 1"
                     /db_xref="GeneID:56384"
                     /db_xref="MGI:MGI:1932557"
     exon            1..244
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     CDS             166..2382
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /note="LETM1 and EF-hand domain-containing protein 1,
                     mitochondrial; mitochondrial proton/calcium exchanger
                     protein; electroneutral mitochondrial K(+)/H(+)exchanger"
                     /codon_start=1
                     /product="mitochondrial proton/calcium exchanger protein
                     precursor"
                     /protein_id="NP_062668.1"
                     /db_xref="CCDS:CCDS19207.1"
                     /db_xref="GeneID:56384"
                     /db_xref="MGI:MGI:1932557"
                     /translation="MASILLRSCRGRGPARLAPPRAASPRGSLRDRACLSCTRTLGLT
                     SRESVLSRCCTPAHPVYLCFKGEPLSCWTQRPECQGTAARTTWTPASARLVVTGPQYL
                     PVRGWHSSSPLGEDSVIEKSLKSLKDKNKKLEEGGPVYSPPAQVVVRKSLGQKVLDEL
                     RHYYHGFRLLWIDTKIAARMLWRILNGHTLTRRERRQFLRICADLFRLVPFLVFVVVP
                     FMEFLLPVVVKLFPNMLPSTFETQSIKEERLKKELRVKLELAKFLQDTIEEMALKNKA
                     AKGNATKDFSAFFQKIRETGERPSNEEIMRFSKLFEDELTLDNLTRPQLVALCKLLEL
                     QSIGTNNFLRFQLTMRLRSIKADDKLISEEGVDSLTVKELQAACRARGMRALGVTEDR
                     LKGQLKQWLDLHLHHEIPTSLLILSRAMYLPDTLSPADQLKSTLQTLPEIVAKEAQVK
                     VAEVEGEKVDNKAKLEATLQEEAAIQQEHLEELKRASEAVKDIQPEVAEATLPGRPGP
                     EPQPPVDDVILPSEVLTDTAPVLEGLKGEEITKEEIDILSDACSKLQEQKKSLTKEKE
                     ELELLKEDVQDYSEDLQEIKKELSKTGEEKYIEESAASKRLSKRVQQMIGQIDGLITQ
                     LETTQQDGKLGPSQSTPTGESVISITELISAMKQIKHIPEHKLISLTSALDDNKDGNI
                     NIDDLVKVIDLVNKEDVQISTTQVAEIVATLEKEEKIEEKEKAKEKAEKEAAEVKN"
     exon            245..305
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            306..756
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            757..900
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            901..1038
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1039..1242
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1243..1362
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1363..1494
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1495..1635
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1636..1770
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1771..1905
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            1906..2093
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            2094..2232
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     exon            2233..5172
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2503..2508
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /note="hexamer: AATAAA"
     polyA_site      2528
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /note="major polyA site"
     regulatory      5148..5153
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Letm1"
                     /gene_synonym="KHE"
                     /note="hexamer: AATAAA"
     polyA_site      5166
                     /gene="Letm1"
                     /gene_synonym="KHE"
ORIGIN      
        1 gtgccgggac atggccgctg cggatgccgg gtccttgagc tgagcgcttg ctgccggagc
       61 caacctctgc cgtcaaccgt ccgcgcgggc tgggcccagg cgccgggacg gccaagatcc
      121 gccgaggaag ctgaggcagc tatagaacgc cgccgcggcg ggcgcatggc gtccatcttg
      181 ctcaggagct gccggggccg ggggcctgcc cgcctcgcgc cacctcgggc cgcctccccg
      241 cggggtagtc tgagggatcg agcttgtctc agctgtacca ggaccctggg gttgacgagc
      301 cgtgagagtg ttctgtctcg ttgctgtact ccagcccacc ctgtgtacct ctgcttcaaa
      361 ggtgagcccc tcagctgttg gactcagagg cctgagtgcc agggcaccgc agcaagaaca
      421 acatggacac ctgcctctgc aaggctggtg gttacgggac ctcagtacct tcctgtgcgc
      481 ggctggcact catcatctcc gctaggagag gactctgtga tagagaagtc ccttaagtcc
      541 ttaaaagaca agaataagaa gctggaggag ggcggccccg tgtacagccc gcccgcgcag
      601 gtggtggtga ggaaatccct cgggcagaag gtactggatg agctgaggca ctactaccat
      661 ggcttccgcc tgctctggat cgacaccaag atcgctgccc ggatgctctg gcgcatcctc
      721 aatggccata cgctgacccg ccgggagcgc aggcagtttc tccggatttg tgcggacctc
      781 ttccgtctag tgcccttcct ggtgttcgtg gtggtgccct tcatggaatt cctgctgcct
      841 gtagttgtga agctcttccc caacatgctg ccctctacat ttgagaccca gtctatcaag
      901 gaggaaaggc tgaagaagga gctgagggtg aagctggagc tggccaagtt tctccaggac
      961 accatagagg aaatggccct gaagaacaag gcagccaaag ggaatgccac caaagatttc
     1021 tctgcatttt tccagaagat ccgggagaca ggggagagac ccagcaatga ggaaatcatg
     1081 cgtttttcca aactgtttga ggatgaactg accctggata acctcacgag gcctcagctg
     1141 gtagcactgt gcaagctgct ggagcttcag tccattggca ccaacaactt cctgcgtttc
     1201 cagctcacca tgcgcctgag gtccataaag gctgatgata agctgatttc tgaggaaggg
     1261 gtggacagtc tgactgtaaa agaattgcag gcagcatgtc gagcacgggg catgagagct
     1321 ctcggtgtca cagaagaccg tctgaagggc cagctgaaac agtggctgga cttgcacctg
     1381 catcacgaga tccccacatc attgctcata ctgtcccggg ccatgtacct cccagacacc
     1441 ctctcacctg ctgaccagct gaagtccacc ttgcagaccc ttccagaaat tgtggcaaag
     1501 gaggcccagg tgaaagtggc cgaggtggag ggcgaaaagg tagacaacaa ggcgaagctg
     1561 gaggccacac tgcaggaaga ggccgccatc cagcaagaac acctggaaga actaaagaga
     1621 gcctctgagg ctgtgaagga catccagcca gaagtagcgg aagccactct ccctgggagg
     1681 ccagggcctg agcctcagcc tccagtggat gatgtgatcc tgccctcaga ggtcctgacg
     1741 gatacggcac ctgtactgga aggtctgaag ggtgaagaga ttaccaagga ggagattgac
     1801 atcctcagtg acgcctgctc caagctgcag gagcagaaga agtccctgac caaggagaag
     1861 gaggagctgg agctgctcaa agaggacgtc caggactaca gtgaggactt acaggagatc
     1921 aagaaggaac tttcaaagac gggtgaggag aagtacatag aagaatctgc agcgagcaag
     1981 aggctgtcaa agcgagtgca gcagatgatc gggcagatcg atggcctgat cacacagctg
     2041 gagaccactc aacaggatgg caagctgggc cccagccaga gcactccaac aggggagagt
     2101 gtcatcagca tcactgagct catcagcgcc atgaagcaaa tcaagcacat tccagagcac
     2161 aagctcatca gtttgacctc agccctggat gataataagg acggcaatat caacatcgat
     2221 gaccttgtca aggtaatcga cttggtgaac aaagaagatg ttcagatctc taccacccag
     2281 gtagctgaaa ttgtggccac actagagaaa gaagaaaaga tagaagagaa agagaaggcc
     2341 aaggagaagg ctgagaaaga ggccgcagaa gtgaagaatt agagctgcca gcttctggcc
     2401 cacaggtctg ccttcatcat gccgtgccag ccacaggggc atgacacaca agagtgattg
     2461 ctttgaggtg attcttagtg gcaaatctaa tattttgtct ggaataaatc agaaacttcc
     2521 ataatgaagc aatttttaat tttcatcatt ccacgaagat tcagtctggc tggagccgga
     2581 gagggtggct ctgtggactc atgctctggt gtggtactga acggccctaa gccttgggtt
     2641 aaggtacagc tgccaatagg atcatagccc tacactgatc cctagcttca gacatggctc
     2701 tggccaggct cagtaggaag gcatttctct gtatgtgtcc ttcctggatc aggatctgag
     2761 cgagcctcca gcctgtgaga ggcgagggag aaccagctgg acctcagcac ctgtgtggag
     2821 cccagagcat gtgtctgcta tgtgtcctca taggccttgg gctaggagtt agataacaca
     2881 gatgcaggcc actctgctct gaggacactg ccgtcagtcc aagggattga gattcccgat
     2941 tgcccatgta catagatgtg tctgctcacg ccttcacagt tgtcataact gcaggtccct
     3001 gacagcagtg tctgtatcct gtatggattc cgagacatgt tgactagcgc tctcttgagt
     3061 tcaccattgg tcaccactta ataattcttt aactgactag tactgacttt tcatacatga
     3121 ccgtctgcct aattcatgag taattcctaa atagtgggtg acatacattg aagaagcctt
     3181 tgaaaatgaa atcttttctg ttgggcattc acattgctga gcaggccttg gggatagaac
     3241 tgacatctgc aacttgaata tacctgaggc tttgtgtggc ttgtaacaga aaattcaagt
     3301 cctaacccac agggcaatgt gcaagatggg gcttcacaag ggaatctctg tatgttgtag
     3361 gctcaaggct ccagcttctt tagcacaaat gttcatggct gtgctccagc caccaagaag
     3421 tgaggaagtt gtactgtgat gccacaaagc tttcagaatg gtgttccctg cccgccaaca
     3481 gttcactggc acccctctaa gtggacagtc tagagctctt tgcctttctc atttggaaat
     3541 ggctccatgg acaggccagg gctgggtgtc ctgtggcctc accaccacct tcacattgta
     3601 accccatcct tggagcgcaa cgggaggaag atcttaagtt cagcttaggc tacttagcaa
     3661 gtccctgtcc aggggaaaaa aaatccttga ctccagacag gatctggaac atgtacagag
     3721 aagcagtgag cagaatggga cattctcagt ttcttgaaac ttctttctta actgttaaag
     3781 gaaacattat gctaagcagg aataaggtga ttcttgcatg taaacctgtg catagtaaca
     3841 gcagaaggag cctagtggct ccgtggttaa atctgaatcc tggtgtccct acgaggacaa
     3901 gattatggtt gccaggtgtg tccccacagt agagggtatc tcctatgacc agcagtctgg
     3961 agctgtcctg tgtctgccca tcgtcttcat cctttagtgt attactgggt actgtcagtg
     4021 gcctgtactg tctgctgctg cctcaggaat tccctactgt acctctaccc tccactctgg
     4081 actctgtcct tgcaggtcac gccatcacct cactgcagga ccttagcaaa cacacgtgct
     4141 aggtctgcca gtggatgctt cccttggttt ttggagttgt cctcacatct gtttgcttaa
     4201 ctgacctggg tcagggttag aaatagcaga tccaccaggc agtgatagca gtgtgcgcct
     4261 ttaatcccag cacttggaag gcaaaggcag gtggacaagc agggctacac agagaaaccc
     4321 tgtctcaaac cactaccacc accaccaccc ccttaaaaaa aagaaatgga ggatccagga
     4381 ctgagacctg tactcagact gagcatttga aagctggctg tatttcaact gtcattctgt
     4441 cctgtacctc agcacttgcc cagggtgtac gttcaggagc tgacatgtct gcacctgtta
     4501 aattaagggt tcaacccagg agcctggcgt ttcctctctc cactctgaac caccttccca
     4561 ccaggatctg gagagctggc acctaaattc caggctcctt ttggcctatt aacatctcaa
     4621 atgtgaaggg taccatacag ttcttaaaag ccattctcat ggtcttaggc tgcgcctcct
     4681 agtaccatgg taggggagca agttctatac cctcttctgt cttccagggg tcccagtgcc
     4741 tccagctaga tcatgtgtag acatctccca tgttcatgta acagcgcaaa gtgatacttc
     4801 tgagccctga gcaatctatt caagacattg agtggaaact cagaccacct tgagctctaa
     4861 tgattgtgct gtggtcacca ggtgtgtttt cggattttag tgggtcttga ctctcccctc
     4921 agcccctagg tgagtgccag ctcgcatttg ggggctcaag ccttggttcc aggctcatga
     4981 cctgtgggac ctatctgagg aagcccatgt acccccatcc tgtgctacag ccctgtttta
     5041 tagaagctga caaggaagga cttcttagac cctaggctaa cccagggccc tgcggggcta
     5101 gcaggcagca tgatgttttc taaacacctt gatgtaagaa ctgactgaat aaagtgccac
     5161 tgatgacttg tcaaaaaaaa aaaaaaaa
//
