KARS1 lysyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KARS1provided by HGNC
Official Full Name: lysyl-tRNA synthetase 1provided by HGNC
Primary source: HGNC:HGNC:6215
See related: Ensembl:ENSG00000065427 MIM:601421; AllianceGenome:HGNC:6215
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; KARS; KARS2; LEPID; CMTRIB; DEAPLE; DFNB89
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]
Expression: Ubiquitous expression in testis (RPKM 57.5), lymph node (RPKM 40.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q23.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (75627724..75647665, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (81676020..81695962, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (75661622..75681563, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Determinants of the interaction between the 5'-leader of HIV-1 genome and human lysyl-tRNA synthetase in reverse transcription primer release process.
Title: Determinants of the interaction between the 5'-leader of HIV-1 genome and human lysyl-tRNA synthetase in reverse transcription primer release process.
Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription.
Title: Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription.
Antibody Deficiency in Patients with Biallelic KARS1 Mutations.
Title: Antibody Deficiency in Patients with Biallelic KARS1 Mutations.
Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.
Title: Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.
Bi-allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease.
Title: Bi-allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease.
Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.
Title: Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.
Structural analyses of a human lysyl-tRNA synthetase mutant associated with autosomal recessive nonsyndromic hearing impairment.
Title: Structural analyses of a human lysyl-tRNA synthetase mutant associated with autosomal recessive nonsyndromic hearing impairment.
Hairpin RNA-induced conformational change of a eukaryotic-specific lysyl-tRNA synthetase extension and role of adjacent anticodon-binding domain.
Title: Hairpin RNA-induced conformational change of a eukaryotic-specific lysyl-tRNA synthetase extension and role of adjacent anticodon-binding domain.
Through whole-exome sequencing, we discovered genetic abnormalities in lysyl-tRNA synthetase (KARS). All patients harboured the variant [c.1786C>T, p.Leu596Phe] KARS isoform 1 ([c.1702C>T, p.Leu568Phe] of KARS isoform 2). These KARS pathological variants are novel, including the variant [c.1786C>T; p.Leu596Phe] (c.1702C>T; p.Leu568Phe) shared by all patients in the homozygous or compound-heterozygous state.
Title: Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy.
This study adds LARS2 and KARS pathogenic variants as gene defects that may underlie deafness, ovarian failure, and leukodystrophy with mitochondrial signature.
Title: Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy.

Submit: New GeneRIF Correction See all GeneRIFs (42)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal recessive nonsyndromic hearing loss 89 MedGen: C3151351 OMIM: 613916 GeneReviews: Not available	not available
Charcot-Marie-Tooth disease recessive intermediate B MedGen: C3150897 OMIM: 613641 GeneReviews: Not available	not available
Deafness, congenital, and adult-onset progressive leukoencephalopathy MedGen: C5543087 OMIM: 619196 GeneReviews: Not available	not available
Leukoencephalopathy, progressive, infantile-onset, with or without deafness MedGen: C5542996 OMIM: 619147 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of lysyl-tRNA synthetase (KARS) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Gag-Pol	gag-pol	The Pol domain of HIV-1 Gag-Pol associates specifically with Lysyl-tRNA synthetase	PubMed
Pol	gag-pol	HIV-1 Pol interacts with lysyl-tRNA synthetase (LysRS). Sequences in Pol binding to LysRS are found within connection domain/RNaseH domain of RT	PubMed
	gag-pol	The p6 and Integrase (IN) domains of HIV-1 Pol act synergistically to build a strong and stable anchoring platform for its binding to LysRS. The catalytic domain (amino acids 237-597) of LysRS is involved in its interaction with Pol	PubMed
Pr55(Gag)	gag	Homodimeric lysyl-tRNA synthetase dissociates into a monomer that bridges between HIV-1 Gag and tRNA(Lys3)	PubMed
	gag	LysRS double mutants at positions I246D/R247A, I250D/I251D, and I254D/R255A in the helix 7 dimerization domain reduce its binding to HIV-1 Gag/delta p6 and CA-CTD	PubMed
	gag	A peptide containing 10 amino acid residues from helix4 of C-terminal domain of HIV-1 CA (CA-CTD) can form a helical structure upon binding to LysRS through strong hydrogen bond interactions between R247-Q219 and R241-E212	PubMed
	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	Mitochondrial localization of lysyl-tRNA synthetase (LysRS) is altered in the presence of HIV-1 Vpr in HeLa cells	PubMed
	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	LysRS double mutants at positions I246D/R247A, I250D/I251D, and I254D/R255A in the helix 7 dimerization domain reduce its binding to HIV-1 Gag/delta p6 and CA-CTD	PubMed
	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
	gag	Cyclic peptides inhibit the interaction of HIV-1 CA with lysyl-tRNA synthetase by binding to the helix 4 motif of the C-terminal domain of CA	PubMed
	gag	Peptides derived from the helix-4 of HIV-1 capsid C-terminal domain significantly bind to LysRS	PubMed
matrix	gag	HIV-1 MA is identified to have a physical interaction with lysyl-tRNA synthetase (KARS) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	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
reverse transcriptase	gag-pol	HIV-1 Pol interacts with lysyl-tRNA synthetase (LysRS). Sequences in Pol binding to LysRS are found within connection domain/RNaseH domain of RT	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-61037 (e-PCR)
- UniSTS:29953

SHGC-61044 (e-PCR)
- UniSTS:35439

D16S2968 (e-PCR)
- UniSTS:3283

RH103951 (e-PCR)
- UniSTS:98276

MARC_13466-13467:1002299828:1 (e-PCR)
- UniSTS:267500

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP:ADP adenylyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP:ADP adenylyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables amino acid binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lysine-tRNA ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables lysine-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables tRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables tRNA binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in basophil activation involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in basophil activation involved in immune response	IGI Inferred from Genetic Interaction more info	PubMed
involved_in diadenosine tetraphosphate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in diadenosine tetraphosphate biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in diadenosine tetraphosphate biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in lysyl-tRNA aminoacylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in lysyl-tRNA aminoacylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of inflammatory response to antigenic stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of macrophage activation	IDA Inferred from Direct Assay more info	PubMed
involved_in response to X-ray	IEA Inferred from Electronic Annotation more info
involved_in tRNA processing	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of aminoacyl-tRNA synthetase multienzyme complex	IBA Inferred from Biological aspect of Ancestor more info
part_of aminoacyl-tRNA synthetase multienzyme complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: lysine--tRNA ligase

Names: lysRS; lysine tRNA ligase

NP_001123561.1

EC 6.1.1.6

NP_001365077.1

EC 6.1.1.6

NP_005539.1

EC 6.1.1.6

NCBI Reference Sequences (RefSeq)

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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), LRG_366

mRNA and Protein(s)

NM_001130089.2 → NP_001123561.1 lysine--tRNA ligase isoform 1

See identical proteins and their annotated locations for NP_001123561.1

Status: REVIEWED

Source sequence(s)

AC025287

Consensus CDS

CCDS45532.1

UniProtKB/Swiss-Prot

Q15046

Related

ENSP00000325448.5, ENST00000319410.9

Conserved Domains (3) summary

PLN02502
Location:48 → 605

PLN02502; lysyl-tRNA synthetase

cd00775
Location:265 → 603

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

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. ...
NM_001378148.1 → NP_001365077.1 lysine--tRNA ligase isoform 3

Status: REVIEWED

Source sequence(s)

AC025287

Conserved Domains (1) summary

PLN02502
Location:1 → 421

PLN02502; lysyl-tRNA synthetase
NM_005548.3 → NP_005539.1 lysine--tRNA ligase isoform 2

See identical proteins and their annotated locations for NP_005539.1

Status: REVIEWED

Source sequence(s)

AA503390, AF285758, AK315687

Consensus CDS

CCDS10923.1

UniProtKB/Swiss-Prot

A8MSK1, D3DUK4, O14946, Q15046, Q96J25, Q9HB23

Related

ENSP00000303043.3, ENST00000302445.8

Conserved Domains (1) summary

PLN02502
Location:12 → 577

PLN02502; lysyl-tRNA synthetase