KARS lysyl-tRNA synthetase [Homo sapiens] - Gene

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Summary

Official Symbol: KARSprovided by HGNC
Official Full Name: lysyl-tRNA synthetaseprovided by HGNC
Primary source: HGNC:6215
See related: Ensembl:ENSG00000065427; HPRD:03249; MIM:601421; Vega:OTTHUMG00000137609
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KRS; KARS2; CMTRIB; KIAA0070
Summary: 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]

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Genomic context

Location :: 16q23.1

Sequence :: Chromosome: 16; NC_000016.9 (75661622..75681585, complement)

See KARS in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data are consistent with hypothesis that maturation of cytoplasmic KARS precursor is needed to reveal the potent tRNA binding properties of mitochondrial KARS.
Title: Activation of human mitochondrial lysyl-tRNA synthetase upon maturation of its premitochondrial precursor.
LysRS associates with the Pol domain of GagPol.
Title: Association of mitochondrial Lysyl-tRNA synthetase with HIV-1 GagPol involves catalytic domain of the synthetase and transframe and integrase domains of Pol.
The results suggest that this unique geometry, which reconfigures the LysRS tetramer from alpha(2):alpha(2) to alpha(2)beta(1):beta(1)alpha(2), is designed to control both retention and mobilization of LysRS from the multi-tRNA synthetase complex
Title: Structural context for mobilization of a human tRNA synthetase from its cytoplasmic complex.
The interaction between helix 7 of LysRS and helix 4 of the capsid C-terminal domain of HIV-1 Gag (HIV-CA-CTD) was studied using circular dichromism spectroscopy and molecular dynamics simulation.
Title: In vitro and in silico binding study of the peptide derived from HIV-1 CA-CTD and LysRS as a potential HIV-1 blocking site.
These results underscore the contribution of KARS to the emission of (one of) the principal signal(s) of immunogenic cell death, CRT exposure.
Title: Lysyl tRNA synthetase is required for the translocation of calreticulin to the cell surface in immunogenic death.
Loss-of-function lysyl-tRNA synthetase mutations associated with peripheral neuropathy and Charcot-Marie-Tooth disease.
Title: Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
mitoKARS is the first described member of a group of mitochondrial proteins whose interaction with mutant SOD1 contributes to mitochondrial dysfunction in ALS
Title: Lysyl-tRNA synthetase is a target for mutant SOD1 toxicity in mitochondria.
present a 2.3-A crystal structure of a tetrameric form of human LysRS
Title: Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation.

Submit: New GeneRIF Correction See all (15)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Charcot-Marie-Tooth disease, recessive intermediate, B

MIM: 613641

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	The interaction of Lysyl-tRNA synthetase with HIV-1 Gag is dependent upon Gag amino acids 310-363 (last 54 amino acids of the capsid domain) and amino acids 208-259 of Lysyl-tRNA synthetase	PubMed
	gag	Lysyl-tRNA synthetase is incorporated into HIV-1 virions through an interaction with HIV-1 Gag	PubMed
Vpr	vpr	HIV-1 Vpr binds to Lysyl-tRNA synthetase (LysRS) and inhibits LysRS-mediated aminoacylation of tRNA-Lys, an effect that may influence the initiation of HIV-1 reverse transcription	PubMed
capsid	gag	The Capsid domain of HIV-1 Gag is sufficient for the interaction of Gag with lysyl-tRNA synthetase in an in vitro pull-down assay	PubMed
retropepsin	gag-pol	Using a bioluminescence resonance energy transfer assay to directly measure HIV-1 protease activity in vivo indicates that the overexpression of lysyl tRNA synthetase (LysRS) in the cell reduces viral protease activity	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005539.1	NP_006294.2	AIMP2	BIND	PubMed	p38 interacts with LysRS.
Q15046	Q13155	AIMP2	HPRD	PubMed
Q15046	P29692	EEF1D	HPRD	PubMed
Q15046	P26641	EEF1G	HPRD	PubMed
Q15046	O43559	FRS3	HPRD	PubMed
Q15046	P57678	GEMIN4	HPRD	PubMed
Q15046	P43034	PAFAH1B1	HPRD	PubMed
Q15046	P12236	SLC25A6	HPRD	PubMed
Q15046	P00441	SOD1	HPRD	PubMed
BioGRID:109938	BioGRID:113684	AIMP2	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:120459	DARS2	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:108257	EEF1G	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:108868	GAPDH	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:109622	ICT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109938	BioGRID:107819	MAPK14	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:110815	NEDD8	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109938	BioGRID:111085	PAFAH1B1	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:114075	PIK3R3	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:111657	PSMA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109938	BioGRID:106790	SLC25A6	BioGRID	PubMed	Two-hybrid
BioGRID:109938	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109938	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109938	BioGRID:113272	VIM	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ligase activity	IEA Inferred from Electronic Annotation more info
lysine-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
lysine-tRNA ligase activity	TAS Traceable Author Statement more info
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleic acid binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
tRNA binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
gene expression	TAS Traceable Author Statement more info
interspecies interaction between organisms	IEA Inferred from Electronic Annotation more info
lysyl-tRNA aminoacylation	IDA Inferred from Direct Assay more info	PubMed
tRNA aminoacylation for protein translation	TAS Traceable Author Statement more info
tRNA processing	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular region	IEA Inferred from Electronic Annotation more info
microtubule cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
nucleus	IEA Inferred from Electronic Annotation more info
plasma membrane	IEA Inferred from Electronic Annotation more info
soluble fraction	TAS Traceable Author Statement more info	PubMed

General protein information

Preferred Names: lysine--tRNA ligase

Names: lysine--tRNA ligase; lysRS; lysine tRNA ligase

NP_001123561.1

EC 6.1.1.6

NP_005539.1

EC 6.1.1.6

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028025.1 RefSeqGene

Range

5001..24964

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001130089.1 → NP_001123561.1 lysine--tRNA ligase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AA503390, AF285758, AK315687, BM781594

Consensus CDS

CCDS45532.1

UniProtKB/Swiss-Prot

Q15046

Related

ENSP00000325448, OTTHUMP00000174949, ENST00000319410, OTTHUMT00000269024

Conserved Domains (3) summary

cd00775
Location:265 – 603
Blast Score: 1440

LysRS_core; Lys_tRNA synthetase (LysRS) class II core domain. Class II LysRS is a dimer which attaches a lysine to the 3' OH group of ribose of the appropriate tRNA. Its assignment to class II aaRS is based upon its structure and the presence of three ...

cd04322
Location:153 – 262
Blast Score: 393

LysRS_N; LysRS_N: N-terminal, anticodon recognition domain of lysyl-tRNA synthetases (LysRS). These enzymes are homodimeric class 2b aminoacyl-tRNA synthetases (aaRSs). This domain is a beta-barrel domain (OB fold) involved in binding the tRNA anticodon stem-loop. ...

PLN02502
Location:91 – 605
Blast Score: 2219

PLN02502; lysyl-tRNA synthetase
NM_005548.2 → NP_005539.1 lysine--tRNA ligase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an internal exon in the 5' region, which results in an upstream AUG start codon, as compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus, as compared to isoform 1.

Source sequence(s)

AA503390, AF285758, AK315687

Consensus CDS

CCDS10923.1

UniProtKB/Swiss-Prot

Q15046

Related

ENSP00000303043, OTTHUMP00000174948, ENST00000302445, OTTHUMT00000269023

Conserved Domains (3) summary

cd00775
Location:237 – 575
Blast Score: 1434

LysRS_core; Lys_tRNA synthetase (LysRS) class II core domain. Class II LysRS is a dimer which attaches a lysine to the 3' OH group of ribose of the appropriate tRNA. Its assignment to class II aaRS is based upon its structure and the presence of three ...

cd04322
Location:125 – 234
Blast Score: 394

LysRS_N; LysRS_N: N-terminal, anticodon recognition domain of lysyl-tRNA synthetases (LysRS). These enzymes are homodimeric class 2b aminoacyl-tRNA synthetases (aaRSs). This domain is a beta-barrel domain (OB fold) involved in binding the tRNA anticodon stem-loop. ...

PLN02502
Location:63 – 577
Blast Score: 2214

PLN02502; lysyl-tRNA synthetase

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p5 Primary Assembly

Range

75661622..75681585, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

61415299..61435262, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC025287.8 (70191..90138)	None
genomic	CH471114.2	EAW95619.1
		EAW95620.1
		EAW95621.1
		EAW95622.1
		EAW95623.1
		EAW95624.1
mRNA	AA503390.1	None
mRNA	AF285758.1	AAG30114.1
mRNA	AK126584.1	BAC86604.1
mRNA	AK309168.1	None
mRNA	AK315687.1	None
mRNA	BC004132.2	AAH04132.1
mRNA	BC013246.1	None
mRNA	BM781594.1	None
mRNA	D31890.1	BAA06688.1
mRNA	D32053.1	BAA22084.1
other-genetic	DQ892301.2	ABM83227.1
other-genetic	DQ895500.2	ABM86426.1