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FLASH GENE

Symbol

KARS

contributors: mct/npt - updated : 16-09-2013

HGNC name	lysyl-tRNA synthetase
HGNC id	6215

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005548 14 - 2017 NP_005539 68 597 - 2012 22235746 cytoplasmic isoform, variant 2 or KARS c splicing exon 1 to exon 3 NM_001130089 15 splicing 2197 NP_001123561 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Reproductive female system uterus cervix   highly Visual eye       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium hair 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