Tchem KARS Lysine--tRNA ligase

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Lysine--trna Ligase

Protein / Ligase / Aminoacyl-trna Synthetase / Lysine--trna Ligase

DTO Classes

Protein / Enzyme / Ligase / Aminoacyl-trna Synthetase / Lysine--trna Ligase

Protein Summary

Description

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. 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]

Uniprot Accession IDs

• Q15046
• A8MSK1
• D3DUK4
• O14946
• Q96J25
• Q9HB23

Gene Name

• KARS

Ensembl ID

• ENST00000302445
• ENSP00000303043
• ENSG00000065427
• ENST00000319410
• ENSP00000325448

Symbol

• KIAA0070
• KRS
• KARS1
• KARS2
• CMTRIB
• DFNB89

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
co-expressed gene	1
interacting protein	1
kinase perturbation	1
molecular function	0.98
protein domain	0.92

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 281.45   (req: < 5)

Gene RIFs: 33   (req: <= 3)

Antibodies: 202   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 281.45   (req: >= 5)

Gene RIFs: 33   (req: > 3)

Antibodies: 202   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 54

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (54)

Explore Active Ligands

1 – 10 of 54

staurosporine

KARSTchem Enzyme

IC50 : 9.07

TAE-684

KARSTchem Enzyme

IC50 : 6.54

CHEMBL459850

KARSTchem Enzyme

EC50 : 7.15

CHEMBL4590082

KARSTchem Enzyme

IC50 : 6.85

Syk inhibitor II

KARSTchem Enzyme

IC50 : 7.39

CHEMBL2178352

KARSTchem Enzyme

IC50 : 6.14

CHEMBL1835870

KARSTchem Enzyme

Ki : 6.66

CHEMBL475575

KARSTchem Enzyme

IC50 : 8.4

CHEMBL474582

KARSTchem Enzyme

IC50 : 8.05

CHEMBL475609

KARSTchem Enzyme

IC50 : 8.05

GWAS Traits (8)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
response to darapladib	EFO_0008395	1	1	0	4.2	33.1
Diarrhea	HP_0002014	1	1	0	4.2	33.1
smoking status measurement	EFO_0006527	1	2	2		33.1
age at first sexual intercourse measurement	EFO_0009749	1	1	1		28.1
smoking initiation	EFO_0005670	1	1	1		26.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
response to darapladib	EFO_0008395	0	4.2	33.1
Diarrhea	HP_0002014	0	4.2	33.1
smoking status measurement	EFO_0006527	2		33.1
age at first sexual intercourse measurement	EFO_0009749	1		28.1
smoking initiation	EFO_0005670	1		26.1

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Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	lysyl-tRNA synthetase	VGNC:13722	454252
Mouse	lysyl-tRNA synthetase	MGI:1934754	85305
Rat	lysyl-tRNA synthetase	RGD:1359653	292028
Dog	lysyl-tRNA synthetase	VGNC:42207	479644
Horse	lysyl-tRNA synthetase	VGNC:19239	100055335

Species	Name	OMA	EggNOG	Inparanoid
Chimp	lysyl-tRNA synthetase
Mouse	lysyl-tRNA synthetase
Rat	lysyl-tRNA synthetase
Dog	lysyl-tRNA synthetase
Horse	lysyl-tRNA synthetase

Protein Structure (5 Structures, 1 AlphaFold Model)

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Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q15046-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (10)

Reactome (8)

KEGG (1)

PathwayCommons (1)

Cytosolic tRNA aminoacylation (R-HSA-379716)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytosolic tRNA aminoacylation	24 targets	R-HSA-379716
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Mitochondrial tRNA aminoacylation	21 targets	R-HSA-379726

Name	Explore in Pharos	Explore in Source
Cytosolic tRNA aminoacylation	24 targets	R-HSA-379716
Metabolism	2112 targets	R-HSA-1430728
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Metabolism of proteins	2050 targets	R-HSA-392499
Mitochondrial tRNA aminoacylation	21 targets	R-HSA-379726

Gene Ontology Terms (33)

Functions (7)

Components (7)

Processes (19)

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10

1 – 7 of 7

GO Term	Evidence	Assigned by
ATP adenylyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
lysine-tRNA ligase activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
tRNA binding	Non-traceable Author Statement (NAS)	UniProtKB
amino acid binding	Inferred from Electronic Annotation (IEA)	Ensembl
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (303)

Explore Interacting Targets

1 – 10 of 303

• See Interactions on String-DB

RARS

Tchem

Family:  Enzyme

Novelty:  0.00099479

p_int:  0.999994549

p_ni:  0.000005451

Score:  0.999

Data Source:  BioPlex,STRINGDB

TARSL2

Tbio

Family:  Enzyme

Novelty:  0.02406282

p_int:  0.999993971

p_ni:  0.000006029

Score:  0.969

Data Source:  BioPlex,STRINGDB

SDCCAG8

Tbio

Novelty:  0.0431837

p_int:  0.999988727

p_ni:  0.000011152

p_wrong:  1.21e-7

Score:  0.741

Data Source:  BioPlex,STRINGDB

AIMP2

Tchem

Family:  Enzyme

Novelty:  0.03283387

p_int:  0.999982175

p_ni:  0.000017825

Score:  0.999

Data Source:  BioPlex,STRINGDB

AIMP1

Tbio

Family:  Enzyme

Novelty:  0.00743447

p_int:  0.9996742

p_ni:  0.0003258

Score:  0.998

Data Source:  BioPlex,STRINGDB

DARS

Tbio

Family:  Enzyme

Novelty:  0.01101888

p_int:  0.999149756

p_ni:  0.000850244

Score:  0.994

Data Source:  BioPlex,STRINGDB

EPRS

Tchem

Family:  Enzyme

Novelty:  0.00084896

p_int:  0.998884029

p_ni:  0.001115971

Score:  0.999

Data Source:  BioPlex,STRINGDB

EEF1E1

Tbio

Novelty:  0.06216577

p_int:  0.998835167

p_ni:  0.001164833

Score:  0.994

Data Source:  BioPlex,STRINGDB

IARS

Tchem

Family:  Enzyme

Novelty:  0.00539046

p_int:  0.998494698

p_ni:  0.001505302

Score:  0.999

Data Source:  BioPlex,STRINGDB

LARS

Tchem

Family:  Enzyme

Novelty:  0.00361711

p_int:  0.998340387

p_ni:  0.001659613

Score:  0.998

Data Source:  BioPlex,STRINGDB

Publication Statistics

PubMed Score  281.45

PubMed score by year

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PubTator Score  138.5

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Aminoacyl-tRNA synthetase
ATP-binding
Cell membrane
Charcot-Marie-Tooth disease
Complete proteome
Cytoplasm
Deafness

GWAS Trait Find Similar Targets

No Header	No Header
age at first sexual intercourse measurement
Diarrhea
response to darapladib
self reported educational attainment
smoking behavior
smoking behaviour measurement
smoking initiation
smoking status measurement

MGI Phenotype Find Similar Targets

No Header	No Header
craniofacial phenotype
mortality/aging
skeleton phenotype