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FLASH GENE
Symbol KARS contributors: mct/npt - updated : 16-09-2013
HGNC name lysyl-tRNA synthetase
HGNC id 6215
Corresponding disease
DFNB89 nonsyndromic hearing impairment locus 89
DICMT4 dominant intermediate Charcot-Marie-Tooth neuropathy 4
Location 16q23.1      Physical location : 75.661.623 - 75.681.585
Synonym name
  • lysine tRNA ligase
  • aminoacyl t-RNA synthetase, class II
  • Synonym symbol(s) KIAA0070, KARS2, LYSRS, KRS, CMTRIB, DFNB89
    EC.number 6.1.1.6
    DNA
    TYPE functioning gene
    STRUCTURE 19.95 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text alternative splicing of the first three exons of the gene
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2017 68 597 - 2012 22235746
  • cytoplasmic isoform, variant 2 or KARS c
  • splicing exon 1 to exon 3
  • 15 splicing 2197 71.4 625 - 2012 22235746
  • mitochondrial isoform, variant 1 or KARS m
  • a 180-bp insertion at the 5'-end of the mRNA
  • carboxyl 576 amino acids are identical to those of the cytoplasmic enzyme but with a different amino terminus of 49 amino acids that contains a putative mitochondrial targeting sequence
  • inclusion of exon 2 between exons 1 and 3
  • first described member of a group of mitochondrial proteins whose interaction with mutant SOD1 contributes to mitochondrial dysfunction in ALS
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
    Reproductivefemale systemuteruscervix highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumhair cell receptor Other species
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PDZ binding motif at its C-terminus (motif important for the interaction of the entire complex with syntenin-1)
  • mono polymer homomer , dimer , tetramer
    HOMOLOGY
    Homologene
    FAMILY
  • class-II aminoacyl-tRNA synthetase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text dual cytosolic and mitochondrial localization (Kawamata 2008)
    basic FUNCTION
  • having aspartate-tRNA ligase activity
  • enzyme required for protein translation, interacting with mutant SOD1 (SOD1 interacts preferentially with the mitochondrial form of KARS) (Kawamata 2008)
  • involved in tRNA packaging
  • catalyzes the aminoacylation of tRNALys in the cytoplasm and mitochondria via a two-step aminoacylation reaction
  • cleavage of the precursor of mitochondrial KARS leads to a mature enzyme with reduced tRNA binding properties compared to those of the cytoplasmic counterpart
  • unique function in the control of cell migration and its pathological implication in metastasis
  • a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of KARS function from translation to transcription
  • presence within inner-ear structures that are involved in mechanotransduction provides further evidence of a role for KARS in hearing
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • direct interaction of SDCBP with lysyl-tRNA synthetase (KARS), which contains a PDZ binding motif at its C-terminus (Meerschaert 2008)
  • interaction with HIV-1 Gag (residues important for homodimerization of Gag and KARS are critical for the Gag/LysRS interaction) (Kovaleski 2006)
  • bound to the multi-tRNA synthetase complex (MSC) that maintains and regulates the aminoacylation and nuclear functions of KARS
  • cell & other
  • target of autoantibodies in autoimmune diseases, polymyositis or dermatomyositis
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DICMT4 , DFNB89
    Susceptibility
    Variant & Polymorphism
    Candidate gene target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis
    Marker
    Therapy target
    ANIMAL & CELL MODELS