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    Letm1 leucine zipper-EF-hand containing transmembrane protein 1 [ Mus musculus (house mouse) ]

    Gene ID: 56384, updated on 27-Nov-2024

    Summary

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    Official Symbol
    Letm1provided by MGI
    Official Full Name
    leucine zipper-EF-hand containing transmembrane protein 1provided by MGI
    Primary source
    MGI:MGI:1932557
    See related
    Ensembl:ENSMUSG00000005299 AllianceGenome:MGI:1932557
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    KHE
    Summary
    Enables calcium:proton antiporter activity. Involved in calcium export from the mitochondrion; mitochondrial calcium ion homeostasis; and protein complex oligomerization. Located in mitochondrial inner membrane. Is expressed in brain; embryo; gonad; liver; and seminiferous cord. Orthologous to human LETM1 (leucine zipper and EF-hand containing transmembrane protein 1). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in duodenum adult (RPKM 18.7), colon adult (RPKM 16.5) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Letm1 in Genome Data Viewer
    Location:
    5 B2; 5 17.83 cM
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (33897017..33940061, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (33739673..33782717, complement)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:34000710-34000897 Neighboring gene STARR-seq mESC enhancer starr_12827 Neighboring gene transmembrane protein 129 Neighboring gene transforming, acidic coiled-coil containing protein 3 Neighboring gene Fgfr3 5' regulatory region Neighboring gene fibroblast growth factor receptor 3 Neighboring gene STARR-seq mESC enhancer starr_12830 Neighboring gene ribosomal protein S29 pseudogene Neighboring gene STARR-positive B cell enhancer ABC_E6319 Neighboring gene ATP synthase subunit g, mitochondrial pseudogene Neighboring gene nuclear receptor binding SET domain protein 2 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:34194226-34194436 Neighboring gene microRNA 7024 Neighboring gene negative elongation factor complex member A, Whsc2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Endoplasmic reticulum potassium-hydrogen exchanger and small conductance calcium-activated potassium channel activities are essential for ER calcium uptake in neurons and cardiomyocytes. Kuum M, et al. J Cell Sci, 2012 Feb 1. PMID 22331352
    2. Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome. Jiang D, et al. Proc Natl Acad Sci U S A, 2013 Jun 11. PMID 23716663, Free PMC Article
    3. PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. Huang E, et al. Nat Commun, 2017 Nov 9. PMID 29123128, Free PMC Article
    4. Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca(2+)/H(+) antiporter. Shao J, et al. Sci Rep, 2016 Sep 27. PMID 27669901, Free PMC Article
    5. LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation. Doonan PJ, et al. FASEB J, 2014 Nov. PMID 25077561, Free PMC Article

    See all (38) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
      Title: PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress.
    2. Reconstitution of LETM1 or antioxidant overexpression rescued mitochondrial Ca(2+) transport and bioenergetics
      Title: LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation.
    3. Data indicate that cellular Letm1 knockdown reduced Ca(2+)mito uptake, H(+)mito extrusion and impaired mitochondrial ATP generation capacity.
      Title: Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf-Hirschhorn syndrome.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (1) 
    • Gene trapped (2)  1 citation

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables calcium:proton antiporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium:proton antiporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium:proton antiporter activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables calcium:proton antiporter activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ribosome binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in calcium export from the mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium export from the mitochondrion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in calcium export from the mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in calcium ion transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in cristae formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cristae formation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in inner mitochondrial membrane organization ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in inner mitochondrial membrane organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in mitochondrial calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion homeostasis ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in mitochondrial calcium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial calcium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial calcium ion transmembrane transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in mitochondrial potassium ion transmembrane transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in mitochondrial potassium ion transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in mitochondrion organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of mitochondrial calcium ion concentration ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in negative regulation of mitochondrial calcium ion concentration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein hexamerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein homooligomerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proton transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cellular hyperosmotic salinity response ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of cellular hyperosmotic salinity response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane HDA PubMed 
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    mitochondrial proton/calcium exchanger protein
    Names
    LETM1 and EF-hand domain-containing protein 1, mitochondrial
    electroneutral mitochondrial K(+)/H(+)exchanger

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_019694.2 → NP_062668.1  mitochondrial proton/calcium exchanger protein precursor

      See identical proteins and their annotated locations for NP_062668.1

      Status: VALIDATED

      Source sequence(s)
      AF061026, AK163499, BQ178952, BY110340, BY243359
      Consensus CDS
      CCDS19207.1
      UniProtKB/Swiss-Prot
      Q5PQC5, Q7TMK8, Q80ZX6, Q8CGJ3, Q8K5E5, Q9Z2I0
      Related
      ENSMUSP00000005431.6, ENSMUST00000005431.6
      Conserved Domains (1) summary
      pfam07766
      Location:154 → 409
      LETM1; LETM1-like protein

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      33897017..33940061 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006504034.5 → XP_006504097.1  mitochondrial proton/calcium exchanger protein isoform X1

      Conserved Domains (1) summary
      pfam07766
      Location:2 → 237
      LETM1; LETM1-like protein
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Z2I0.1 GenPept UniProtKB/Swiss-Prot:Q9Z2I0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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