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  5. Lysine--tRNA ligase

Tchem Lysine--tRNA ligase

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. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. 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]

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Property Summary

NCBI Gene PubMed Count 56
Grant Count 116
R01 Count 83
Funding $20,515,824.93
PubMed Score 265.80
PubTator Score 139.11

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (21)

Disease Z-score Confidence
Attention deficit hyperactivity disorder 156 4.339 2.2
Epilepsy 346 3.711 1.9
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE I... 1 
Charcot-Marie-Tooth disease 74 4.0
DEAFNESS, AUTOSOMAL RECESSIVE 89 1
Multiple myeloma 1,327
Neurodegenerative disease 383 4.0
Neuropathy 210 4.0
Nonsyndromic deafness 121 4.0
Subcutaneous panniculitis-like T-cell ly... 16 
Waldenstrons macroglobulinemia 765
acute myeloid leukemia 780
astrocytoma 1,493
dermatomyositis 933
diabetes mellitus 1,663
lung cancer 4,466
medulloblastoma, large-cell 6,234
mucosa-associated lymphoid tissue lympho... 480 
ovarian cancer 8,484
psoriasis 6,685
sonic hedgehog group medulloblastoma 1,482

Expression

  Differential Expression (13)

Disease log2 FC p
Waldenstrons macroglobulinemia 1.549 0.009
Multiple myeloma 1.226 0.001
psoriasis 1.400 0.000
astrocytoma 1.400 0.002
medulloblastoma, large-cell 1.200 0.000
lung cancer 1.100 0.003
diabetes mellitus -1.600 0.001
sonic hedgehog group medulloblastoma 1.100 0.000
Subcutaneous panniculitis-like T-cell ly... 1.600 0.029
mucosa-associated lymphoid tissue lympho... -1.009 0.006
acute myeloid leukemia 1.700 0.027
ovarian cancer 2.400 0.000
dermatomyositis 1.400 0.001

Synonym

Accession Q15046 A8MSK1 D3DUK4 O14946 Q96J25 Q9HB23
Symbols KRS
KARS1
KARS2
CMTRIB
DFNB89

Gene

KARS

PANTHER Protein Class (2)

 Grant Application (116)

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PDB

3BJU   4DPG   4YCU   4YCW  

 GO Function (5)

 GO Component (9)

 GO Process (5)

 Compartment GO Term (43)

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 IMPC Term (4)

 OMIM Term (2)

 MGI Term (3)

Pathway (11)

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 UniProt Keyword (27)

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Ligand (45)

Structure of CHEMBL479820

CHEMBL479820
pIC50 6.12

Structure of CHEMBL2178352

CHEMBL2178352
pIC50 6.14

Structure of CHEMBL511829

CHEMBL511829
pIC50 6.16

Structure of CHEMBL2069334

CHEMBL2069334
pIC50 6.28

Structure of CHEMBL2069342

CHEMBL2069342
pIC50 6.35

Structure of CHEMBL509032

CHEMBL509032
pIC50 6.54

Structure of CHEMBL482175

CHEMBL482175
pIC50 6.64

Structure of CHEMBL1835870

CHEMBL1835870
pKi 6.66

Structure of CHEMBL2069336

CHEMBL2069336
pIC50 6.70

Structure of CHEMBL2069340

CHEMBL2069340
pIC50 6.80

Structure of CHEMBL476741

CHEMBL476741
pIC50 6.82

Structure of CHEMBL475882

CHEMBL475882
pIC50 6.92

Structure of CHEMBL2069343

CHEMBL2069343
pIC50 6.94

Structure of CHEMBL2069337

CHEMBL2069337
pIC50 7.04

Structure of CHEMBL478642

CHEMBL478642
pIC50 7.08

Structure of CHEMBL2323631

CHEMBL2323631
pIC50 7.10

Structure of CHEMBL459850

CHEMBL459850
pEC50 7.15

Structure of CHEMBL2323635

CHEMBL2323635
pIC50 7.15

Structure of CHEMBL2323632

CHEMBL2323632
pIC50 7.15

Structure of CHEMBL2323633

CHEMBL2323633
pIC50 7.19

Gene RIF (80)

PMID Text
26643967 finding show that enzymatically active Shiga toxins trigger the dissociation of lysyl-tRNA synthetase (KRS) from the multi-aminoacyl-tRNA synthetase complex in human macrophage-like differentiated THP-1 cells and its subsequent secretion.
26091349 KRS at the plasma membrane plays new roles in metastatic migration as a signaling inducer, and causes intracellular signaling for cancer dissemination
25918939 tRK1 forms a complex with human enolases and interacts with tRK1 and human pre-lysyl-tRNA synthetase (preKARS2)
25010285 Homodimeric lysyl-tRNA synthetase dissociates into a monomer that bridges between HIV-1 Gag and tRNA(Lys3)
24983501 structural characteristics of the KRS-LR interaction on the cell surface
23972532 Lysyl-tRNA synthetase plays essential role in HIV replication, transcriptional regulation, cytokine-like signaling. [review]
23799079 The role of preKARS2 in the tRNA mitochondrial import.
23768514 The KARS variant is identified in two families affected by DFNB89-associated autosomal-recessive nonsyndromic hearing impairment.
23208549 C-terminal domain of HIV-1 capsid protein as surrogate for human lysyl tRNA synthetase
23208549 Homodimeric lysyl-tRNA synthetase dissociates into a monomer that bridges between HIV-1 Gag and tRNA(Lys3)
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AA Sequence 

MAAVQAAEVKVDGSEPKLSKNELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTTDNGVGPEEES      1 - 70
VDPNQYYKIRSQAIHQLKVNGEDPYPHKFHVDISLTDFIQKYSHLQPGDHLTDITLKVAGRIHAKRASGG     71 - 140
KLIFYDLRGEGVKLQVMANSRNYKSEEEFIHINNKLRRGDIIGVQGNPGKTKKGELSIIPYEITLLSPCL    141 - 210
HMLPHLHFGLKDKETRYRQRYLDLILNDFVRQKFIIRSKIITYIRSFLDELGFLEIETPMMNIIPGGAVA    211 - 280
KPFITYHNELDMNLYMRIAPELYHKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDL    281 - 350
MEITEKMVSGMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETR    351 - 420
KILDDICVAKAVECPPPRTTARLLDKLVGEFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFV    421 - 490
MKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEYGLPPTAGWGMGIDRVAMFLTD    491 - 560
SNNIKEVLLFPAMKPEDKKENVATTDTLESTTVGTSV                                     561 - 597
//

Text Mined References (68)

PMID Year Title
26643967 2016 Shiga Toxins Trigger the Secretion of Lysyl-tRNA Synthetase to Enhance Proinflammatory Responses.
26091349 2015 Noncanonical roles of membranous lysyl-tRNA synthetase in transducing cell-substrate signaling for invasive dissemination of colon cancer spheroids in 3D collagen I gels.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25918939 2015 A Moonlighting Human Protein Is Involved in Mitochondrial Import of tRNA.
25416956 2014 A proteome-scale map of the human interactome network.
25086665 2014 Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
24983501 2014 Characterization of the interaction between lysyl-tRNA synthetase and laminin receptor by NMR.
23972532 2013 Non-canonical roles of lysyl-tRNA synthetase in health and disease.
23799079 2013 Induced tRNA import into human mitochondria: implication of a host aminoacyl-tRNA-synthetase.
23768514 2013 Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89.
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