Lysine--tRNA ligase

Details

Name

Lysine--tRNA ligase

Synonyms

• 6.1.1.6
• KIAA0070
• LysRS
• Lysyl-tRNA synthetase

Gene Name

KARS

Organism

Humans

Amino acid sequence

>lcl|BSEQ0000395|Lysine--tRNA ligase
MAAVQAAEVKVDGSEPKLSKNELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTT
DNGVGPEEESVDPNQYYKIRSQAIHQLKVNGEDPYPHKFHVDISLTDFIQKYSHLQPGDH
LTDITLKVAGRIHAKRASGGKLIFYDLRGEGVKLQVMANSRNYKSEEEFIHINNKLRRGD
IIGVQGNPGKTKKGELSIIPYEITLLSPCLHMLPHLHFGLKDKETRYRQRYLDLILNDFV
RQKFIIRSKIITYIRSFLDELGFLEIETPMMNIIPGGAVAKPFITYHNELDMNLYMRIAP
ELYHKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVSG
MVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETR
KILDDICVAKAVECPPPRTTARLLDKLVGEFLEVTCINPTFICDHPQIMSPLAKWHRSKE
GLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEYG
LPPTAGWGMGIDRVAMFLTDSNNIKEVLLFPAMKPEDKKENVATTDTLESTTVGTSV

Number of residues

597

Molecular Weight

68047.54

Theoretical pI

6.31

GO Classification

Functions

amino acid binding / ATP binding / lysine-tRNA ligase activity / metal ion binding / tRNA binding

Processes

diadenosine tetraphosphate biosynthetic process / gene expression / lysyl-tRNA aminoacylation / tRNA aminoacylation for protein translation / tRNA processing / viral process

Components

aminoacyl-tRNA synthetase multienzyme complex / cytoplasm / cytosol / extracellular region / microtubule cytoskeleton / mitochondrial matrix / mitochondrion / nucleus / plasma membrane

General Function

Trna binding

Specific Function

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.

Pfam Domain Function

• tRNA-synt_2 (PF00152)
• tRNA_anti-codon (PF01336)

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0010196|Lysine--tRNA ligase (KARS)
ATGTTGACGCAAGCTGCTGTAAGGCTTGTTAGGGGGTCCCTGCGCAAAACCTCCTGGGCA
GAGTGGGGTCACAGGGAACTGCGACTGGGTCAACTTGCTCCTTTCACAGCGCCTCACAAG
GACAAGTCATTTTCTGATCAAAGAAGTGAGCTGAAGAGACGCCTGAAAGCTGAGAAGAAA
GTAGCAGAGAAGGAGGCCAAACAGAAAGAGCTCAGTGAGAAACAGCTAAGCCAAGCCACT
GCTGCTGCCACCAACCACACCACTGATAATGGTGTGGGTCCTGAGGAAGAGAGCGTGGAC
CCAAATCAATACTACAAAATCCGCAGTCAAGCAATTCATCAGCTGAAGGTCAATGGGGAA
GACCCATACCCACACAAGTTCCATGTAGACATCTCACTCACTGACTTCATCCAAAAATAT
AGTCACCTGCAGCCTGGGGATCACCTGACTGACATCACCTTAAAGGTGGCAGGTAGGATC
CATGCCAAAAGAGCTTCTGGGGGAAAGCTCATCTTCTATGATCTTCGAGGAGAGGGGGTG
AAGTTGCAAGTCATGGCCAATTCCAGAAATTATAAATCAGAAGAAGAATTTATTCATATT
AATAACAAACTGCGTCGGGGAGACATAATTGGAGTTCAGGGGAATCCTGGTAAAACCAAG
AAGGGTGAGCTGAGCATCATTCCGTATGAGATCACACTGCTGTCTCCCTGTTTGCATATG
TTACCTCATCTTCACTTTGGCCTCAAAGACAAGGAAACAAGGTATCGCCAGAGATACTTG
GACTTGATCCTGAATGACTTTGTGAGGCAGAAATTTATCATCCGCTCTAAGATCATCACA
TATATAAGAAGTTTCTTAGATGAGCTGGGATTCCTAGAGATTGAAACTCCCATGATGAAC
ATCATCCCAGGGGGAGCCGTGGCCAAGCCTTTCATCACTTATCACAACGAGCTGGACATG
AACTTATATATGAGAATTGCTCCAGAACTCTATCATAAGATGCTTGTGGTTGGTGGCATC
GACCGGGTTTATGAAATTGGACGCCAGTTCCGGAATGAGGGGATTGATTTGACGCACAAT
CCTGAGTTCACCACCTGTGAGTTCTACATGGCCTATGCAGACTATCACGATCTCATGGAA
ATCACGGAGAAGATGGTTTCAGGGATGGTGAAGCATATTACAGGCAGTTACAAGGTCACC
TACCACCCAGATGGCCCAGAGGGCCAAGCCTACGATGTTGACTTCACCCCACCCTTCCGG
CGAATCAACATGGTAGAAGAGCTTGAGAAAGCCCTGGGGATGAAGCTGCCAGAAACGAAC
CTCTTTGAAACTGAAGAAACTCGCAAAATTCTTGATGATATCTGTGTGGCAAAAGCTGTT
GAATGCCCTCCACCTCGGACCACAGCCAGGCTCCTTGACAAGCTTGTTGGGGAGTTCCTG
GAAGTGACTTGCATCAATCCTACATTCATCTGTGATCACCCACAGATAATGAGCCCTTTG
GCTAAATGGCACCGCTCTAAAGAGGGTCTGACTGAGCGCTTTGAGCTGTTTGTCATGAAG
AAAGAGATATGCAATGCGTATACTGAGCTGAATGATCCCATGCGGCAGCGGCAGCTTTTT
GAAGAACAGGCCAAGGCCAAGGCTGCAGGTGATGATGAGGCCATGTTCATAGATGAAAAC
TTCTGTACTGCCCTGGAATATGGGCTGCCCCCCACAGCTGGCTGGGGCATGGGCATTGAT
CGAGTCGCCATGTTTCTCACGGACTCCAACAACATCAAGGAAGTACTTCTGTTTCCTGCC
ATGAAACCCGAAGACAAGAAGGAGAATGTAGCAACCACTGATACACTGGAAAGCACAACA
GTTGGCACTTCTGTCTAG

Chromosome Location

16

Locus

16q23-q24

External Identifiers

Resource	Link
UniProtKB ID	Q15046
UniProtKB Entry Name	SYK_HUMAN
GenBank Protein ID	505108
GenBank Gene ID	D31890
GenAtlas ID	KARS
HGNC ID	HGNC:6215

General References

1. Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P: Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant. J Biol Chem. 1997 Sep 5;272(36):22809-16. [Article]
2. Tolkunova E, Park H, Xia J, King MP, Davidson E: The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript. J Biol Chem. 2000 Nov 10;275(45):35063-9. [Article]
3. Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S: Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1994;1(5):223-9. [Article]
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6. Zamecnik PC, Stephenson ML, Janeway CM, Randerath K: Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase. Biochem Biophys Res Commun. 1966 Jul 6;24(1):91-7. [Article]
7. Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M: Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein. J Mol Biol. 1999 Jan 8;285(1):183-95. [Article]
8. Tan M, Wei C, Price CM: The telomeric protein Rap1 is conserved in vertebrates and is expressed from a bidirectional promoter positioned between the Rap1 and KARS genes. Gene. 2003 Dec 24;323:1-10. [Article]
9. Lee YN, Nechushtan H, Figov N, Razin E: The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity. 2004 Feb;20(2):145-51. [Article]
10. Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsyth K, Gottlinger H, Kleiman L: The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly. J Biol Chem. 2003 Jul 25;278(30):27644-51. Epub 2003 May 19. [Article]
11. Halwani R, Cen S, Javanbakht H, Saadatmand J, Kim S, Shiba K, Kleiman L: Cellular distribution of Lysyl-tRNA synthetase and its interaction with Gag during human immunodeficiency virus type 1 assembly. J Virol. 2004 Jul;78(14):7553-64. [Article]
12. Park SG, Kim HJ, Min YH, Choi EC, Shin YK, Park BJ, Lee SW, Kim S: Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc Natl Acad Sci U S A. 2005 May 3;102(18):6356-61. Epub 2005 Apr 25. [Article]
13. Guzzo CM, Yang DC: Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro. Biochem Biophys Res Commun. 2008 Jan 25;365(4):718-23. Epub 2007 Nov 20. [Article]
14. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
15. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
17. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
18. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
19. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
20. Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL: Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. doi: 10.1073/pnas.0712072105. Epub 2008 Feb 13. [Article]
21. McLaughlin HM, Sakaguchi R, Liu C, Igarashi T, Pehlivan D, Chu K, Iyer R, Cruz P, Cherukuri PF, Hansen NF, Mullikin JC, Biesecker LG, Wilson TE, Ionasescu V, Nicholson G, Searby C, Talbot K, Vance JM, Zuchner S, Szigeti K, Lupski JR, Hou YM, Green ED, Antonellis A: Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet. 2010 Oct 8;87(4):560-6. doi: 10.1016/j.ajhg.2010.09.008. [Article]
22. Santos-Cortez RL, Lee K, Azeem Z, Antonellis PJ, Pollock LM, Khan S, Irfanullah, Andrade-Elizondo PB, Chiu I, Adams MD, Basit S, Smith JD, Nickerson DA, McDermott BM Jr, Ahmad W, Leal SM: Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am J Hum Genet. 2013 Jul 11;93(1):132-40. doi: 10.1016/j.ajhg.2013.05.018. Epub 2013 Jun 13. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB00123	Lysine	approved, nutraceutical	unknown		Details