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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
    Physical map
    LOC388292 16 similar to NPIP-like protein LOC388293 16 similar to nuclear pore complex interacting protein LOC388294 16 similar to secretory protein LOC348174 LOC388295 16 LOC388295 GLG1 16q22-q23 golgi apparatus protein 1 FLJ10520 16q22.3 hypothetical protein FLJ10520 FLJ34389 16q22.3 hypothetical protein FLJ34389 FA2H 16q23 fatty acid 2-hydroxylase FLJ12270 16q22.3 hypothetical protein FLJ12270 ZNRF1 16q22.3 zinc and ring finger protein 1 LDHD 16q22.3 lactate dehydrogenase D ZFP1 16q22.3 zinc finger protein 1 homolog (mouse) CTRB1 16q23.1-q23.2 chymotrypsinogen B1 LOC390741 16 similar to 40S ribosomal protein S4, Y isoform LOC339102 16q22.3 similar to Chymotrypsinogen B precursor LOC146599 16q22.3 hypothetical LOC146599 BCAR1 16q22-q23 breast cancer anti-estrogen resistance 1 LOC388296 16 LOC388296 CFDP1 16q22.2-q22.3 craniofacial development protein 1 LOC388297 16 similar to hypothetical protein - fruit fly (Drosophila melanogaster) transposon pogoR11 LOC124491 16q22.3 LOC124491 CHST6 16q22 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 6 LOC388298 16 LOC388298 CHST5 16q23.1 carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 GABARAPL2 16q22.3-q24.1 GABA(A) receptor-associated protein-like 2 ADAT1 16q22.2-q22.3 adenosine deaminase, tRNA-specific 1 KARS 16q23-q24 lysyl-tRNA synthetase TERF2IP 16q22.3 telomeric repeat binding factor 2, interacting protein LOC342409 16q23.1 similar to Hypothetical protein MGC67567 LOC124496 16q23.1 similar to ATP synthase B chain, mitochondrial precursor LOC124321 16q23.1 similar to ribosomal protein L18; 60S ribosomal protein L18 CASPR4  cell recognition protein CASPR4
    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