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FLASH GENE
Symbol LETM1 contributors: mct - updated : 09-11-2022
HGNC name leucine zipper-EF-hand containing transmembrane protein 1
HGNC id 6556
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
blood / hematopoieticthymus   highly
Digestivesalivary gland   highly
Nervousbrain    
Reproductivefemale systembreastmammary gland highly
Respiratorylung    
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Connectivebonesubchondral  
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal extracellular domain, with mitochondrial targeting sequences
  • a transmembrane segment (TM1),two EF-hand calcium Ca2 + binding sites
  • a C terminal leucine-zipper and phosphorylation sites
  • secondary structure an alpha helical domain forming a coiled coil
    HOMOLOGY
    interspecies ortholog to murine Letm1
    homolog to C.elegans F58G11.1b
    ortholog to yeast YOL027
    homolog to to yeast Mdm38
    intraspecies homolog to LETM2
    Homologene
    FAMILY
  • EF-hand family of calcium-binding proteins
  • mitochondrial transporter protein SLC55 family
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • in the inner mitochondrial membrane
  • reside in the ER membrane
  • basic FUNCTION
  • may be involved in Ca(2+) signaling and/or homeostasis
  • playing a role in mitochondrial morphology
  • encoding factors involved in both K+ homeostasis and organelle volume control
  • regulates the volume of the mitochondrial matrix
  • binding partner for THEM4 that may play an important role in mitochondrial fragmentation via OPA1-cleavage
  • serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis
  • plays an essential role in mitochondrial K+ homeostasis by mediating the mitochondrial K+/H+ exchange that is of prime importance for organelle-volume control
  • acts as an anchor protein and associates with mitochondrial ribosome protein L36
  • served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis
  • mitochondrial Ca2+/H+ antiporter that achieved mitochondrial Ca2+ sequestration at small Ca2+ increases
  • LETM1 and UCP2/3 independently contribute to two distinct, mitochondrial Ca2+ uptake pathways in intact endothelial cells
  • its activity is essential for ER Ca(2+) uptake
  • SLC8B1 but not LETM1, mediates Ca(2+) extrusion from mitochondria
  • role of LETM1-dependent mitochondrial Ca(2+) flux in shaping cellular bioenergetics
  • LETM1 is a Ca2+/H+ antiporter and most likely responsible for mitochondrial Ca2+ output
  • key role of LETM1 in monovalent cation homeostasis, suggesting that the effects of its modulation on mitochondrial transmembrane Ca2+ fluxes may reflect those on Na+/H+ exchange activity
  • LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration
  • remarkable role of LETM1 in mitochondrial network physiology and in mitochondrion&
  • 8209;mediated cell death
  • LETM1 plays likely a fundamental role in the organization of mitochondrial membrane morphology
  • encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis
  • LETM1 function is required for the maintenance of mitochondrial cationic and osmotic balance
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • function of LETM1 in mitochondria regulation is regulated by its binding partners, C&
  • 8209;terminal modulator protein and mitochondrial ribosomal protein L36
    cell & other
    REGULATION
    Other regulated by BCS1L (stimulates the assembly of the LETM1 complex)
    ASSOCIATED DISORDERS
    corresponding disease(s) CONDMIM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in most patients with the Wolf-Hirschhorn syndrome exhibiting seizures and putative contributor to the phenotype, but preserved in those without seizures
    tumoral     --over  
    significantly increased in multiple human cancer tissues compared with normals
    tumoral     --over  
    is associated with the poor progression of gastric adenocarcinoma (GA)
    tumoral        
    suppressed cancer stem cell-like properties and induced autophagy in colorectal cancer (CRC) cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene for seizures in Wolf-Hirschhorn syndrome
    Marker
  • could serve as a potential prognostic biomarker of gastric adenocarcinoma (GA)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment
    cancerdigestivestomach
    could serve as a therapeutic target for the better clinical management of GA
    cancerdigestivecolon
    Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy
    ANIMAL & CELL MODELS