KARS1

Protein identityUniProt · HPA

UniProt accession

Q15046

Gene

KARS1

Ensembl

ENSG00000065427

Chromosome

16

Canonical length

597 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

597 residues, UniProt reviewed canonical sequence.

>Q15046|KARS1
     1  MAAVQAAEVK VDGSEPKLSK NELKRRLKAE KKVAEKEAKQ KELSEKQLSQ ATAAATNHTT
    61  DNGVGPEEES VDPNQYYKIR SQAIHQLKVN GEDPYPHKFH VDISLTDFIQ KYSHLQPGDH
   121  LTDITLKVAG RIHAKRASGG KLIFYDLRGE GVKLQVMANS RNYKSEEEFI HINNKLRRGD
   181  IIGVQGNPGK TKKGELSIIP YEITLLSPCL HMLPHLHFGL KDKETRYRQR YLDLILNDFV
   241  RQKFIIRSKI ITYIRSFLDE LGFLEIETPM MNIIPGGAVA KPFITYHNEL DMNLYMRIAP
   301  ELYHKMLVVG GIDRVYEIGR QFRNEGIDLT HNPEFTTCEF YMAYADYHDL MEITEKMVSG
   361  MVKHITGSYK VTYHPDGPEG QAYDVDFTPP FRRINMVEEL EKALGMKLPE TNLFETEETR
   421  KILDDICVAK AVECPPPRTT ARLLDKLVGE FLEVTCINPT FICDHPQIMS PLAKWHRSKE
   481  GLTERFELFV MKKEICNAYT ELNDPMRQRQ LFEEQAKAKA AGDDEAMFID ENFCTALEYG
   541  LPPTAGWGMG IDRVAMFLTD SNNIKEVLLF PAMKPEDKKE NVATTDTLES TTVGTSV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KARS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

206 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KARS1.

Disease | AllUniProt

Conditions KARS1 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, recessive intermediate B (CMTRIB) MIM:613641
• Deafness, autosomal recessive, 89 (DFNB89) MIM:613916
• Deafness, congenital, and adult-onset progressive leukoencephalopathy (DEAPLE) MIM:619196
• Leukoencephalopathy, progressive, infantile-onset, with or without deafness (LEPID) MIM:619147

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 553 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Leukoencephalopathy, progressive, infantile-onset, with or without deafness
• Autosomal recessive nonsyndromic hearing loss 89
• LEUKOENCEPHALOPATHY, PROGRESSIVE, INFANTILE-ONSET, WITH DEAFNESS
• Deafness, congenital, and adult-onset progressive leukoencephalopathy
• Charcot-Marie-Tooth disease recessive intermediate B

Disease | ImmuneIEDB

Conditions an epitope on KARS1 was assayed in.

• sarcoidosis T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.91

gnomAD pLI

0

DepMap mean gene effect

-1.65

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• basophil activation involved in immune response
• diadenosine tetraphosphate biosynthetic process
• ERK1 and ERK2 cascade
• positive regulation of DNA-templated transcription
• positive regulation of inflammatory response to antigenic stimulus
• positive regulation of macrophage activation
• response to X-ray
• tRNA processing
• lysyl-tRNA aminoacylation

Molecular functions

• amino acid binding
• ATP binding
• identical protein binding
• protein homodimerization activity
• tRNA binding
• ATP:ADP adenylyltransferase activity
• lysine-tRNA ligase activity

Cellular components

• aminoacyl-tRNA synthetase multienzyme complex
• cytoplasm
• cytosol
• extracellular space
• mitochondrial matrix
• mitochondrion
• nucleoplasm
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Aminoacyl-tRNA synthetase, class II (D/K/N)
• OB-fold nucleic acid binding domain, AA-tRNA synthetase-type
• Aminoacyl-tRNA synthetase, class II
• Nucleic acid-binding, OB-fold
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• tRNA synthetases class II (D, K and N)
• OB-fold nucleic acid binding domain
• Lysine-tRNA ligase, class II
• Lysyl-tRNA synthetase, class II, C-terminal
• Bacterial/eukaryotic lysine-tRNA ligase, class II
• Lysine-tRNA ligase, class II, N-terminal

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Cell membrane
• Charcot-Marie-Tooth disease
• Cytoplasm
• Deafness
• Host-virus interaction
• Intellectual disability
• Ligase
• Membrane
• Mitochondrion
• Neurodegeneration
• Neuropathy
• Non-syndromic deafness
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Protein biosynthesis
• Secreted
• Transferase

InteractionsUniProt · HPA

Protein binding partners of KARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AIMP2
• TARSL2
• MITF
• TARS3
• EEF1A1
• EPRS1
• RPSA