KARS (gene)

Last updated
KARS1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases KARS1 , KARS2, CMTRIB, lysyl-tRNA synthetase 1, KRS, Lysyl-tRNA synthetase, KARS, DFNB89, LEPID, DEAPLE
External IDs OMIM: 601421 MGI: 1934754 HomoloGene: 4053 GeneCards: KARS1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005548
NM_001130089
NM_001378148

NM_001130868
NM_001286384
NM_053092
NM_001363429
NM_001363430

Contents

RefSeq (protein)

NP_001123561
NP_005539
NP_001365077

NP_001124340
NP_001273313
NP_444322
NP_001350358
NP_001350359

Location (UCSC) Chr 16: 75.63 – 75.65 Mb Chr 8: 112.72 – 112.74 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARS gene. [5] [6] [7]

Function

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 [7]

Besides its role in translation, Lysyl-tRNA synthetase is involved in a signaling pathway leading to gene activation. [8] Following physiological stimulation of a variety of cells, Lysyl-tRNA synthetase binds to the transcription factors MITF [9] and USF2 [10] and can then influence their transcriptional activities. Such physiological stimulation includes immunological activation of mast cells, so this pathway maybe relevant to the allergic response.

Interactions

KARS (gene) has been shown to interact with Multisynthetase complex auxiliary component p38. [11] [12] Physiological trigger such as immunological activation results in the phosphorylation of LysRS on its serine residues. It separates from the multisynthetase complex and initiates Ap4A production. [8]

Related Research Articles

<span class="mw-page-title-main">Pyrrolysine</span> Chemical compound

Pyrrolysine is an α-amino acid that is used in the biosynthesis of proteins in some methanogenic archaea and bacteria; it is not present in humans. It contains an α-amino group, a carboxylic acid group. Its pyrroline side-chain is similar to that of lysine in being basic and positively charged at neutral pH.

<span class="mw-page-title-main">Aminoacyl tRNA synthetase</span> Class of enzymes

An aminoacyl-tRNA synthetase, also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.

<span class="mw-page-title-main">Microphthalmia-associated transcription factor</span> Mammalian protein found in Homo sapiens

Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene.

<span class="mw-page-title-main">MAPK14</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.

<span class="mw-page-title-main">EEF1D</span> Protein-coding gene in the species Homo sapiens

Elongation factor 1-delta is a protein that in humans is encoded by the EEF1D gene.

<span class="mw-page-title-main">Eukaryotic translation elongation factor 1 alpha 1</span> Constitutive promoter

Elongation factor 1-alpha 1 (eEF1a1) is a translation elongation protein, expressed across eukaryotes. In humans, it is encoded by the EEF1A1 gene.

<span class="mw-page-title-main">EPRS</span> Protein-coding gene in the species Homo sapiens

Bifunctional aminoacyl-tRNA synthetase is an enzyme that in humans is encoded by the EPRS gene.

<span class="mw-page-title-main">HARS</span> Protein-coding gene in the species Homo sapiens

Histidyl-tRNA synthetase (HARS) also known as histidine-tRNA ligase, is an enzyme which in humans is encoded by the HARS gene.

<span class="mw-page-title-main">RARS (gene)</span> Protein-coding gene in the species Homo sapiens

Arginyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the RARS gene.

<span class="mw-page-title-main">DARS (gene)</span> Protein-coding gene in the species Homo sapiens

Aspartyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the DARS gene.

<span class="mw-page-title-main">Multisynthetase complex auxiliary component p38</span> Protein-coding gene in the species Homo sapiens

Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 is an enzyme that in humans is encoded by the AIMP2 gene.

<span class="mw-page-title-main">Leucyl-tRNA synthetase</span> Protein-coding gene in the species Homo sapiens

Leucyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the LARS gene.

<span class="mw-page-title-main">QARS</span> Protein-coding gene in the species Homo sapiens

Glutaminyl-tRNA synthetase is an enzyme that in humans is encoded by the QARS gene.

<span class="mw-page-title-main">MARS (gene)</span>

Methionyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the MARS gene.

<span class="mw-page-title-main">HINT1</span> Protein-coding gene in the species Homo sapiens

Histidine triad nucleotide-binding protein 1 also known as adenosine 5'-monophosphoramidase is an enzyme that in humans is encoded by the HINT1 gene.

<span class="mw-page-title-main">IARS</span> Protein-coding gene in the species Homo sapiens

Isoleucyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the IARS1 gene.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

Diadenosine tetraphosphate or Ap4A is a putative alarmone, ubiquitous in nature being common to everything from bacteria to humans. It is made up of two adenosines joined together by a 5′-5′ linked chain of four phosphates. Adenosine polyphosphates are capable of inducing multiple physiological effects.

Karin Musier-Forsyth, an American biochemist, is an Ohio Eminent Scholar on the faculty of the Department of Chemistry & Biochemistry at Ohio State University. Musier-Forsyth's research involves biochemical, biophysical and cell-based approaches to understand the interactions of proteins and RNAs involved in protein synthesis and viral replication, especially in HIV.

Xiang-Lei Yang (杨湘磊) is a Chinese-born American molecular biologist. She is a professor at The Scripps Research Institute, located in La Jolla, California. Her work has contributed to the establishment of physiological importance of aminoacyl-tRNA synthetases beyond their classical role in supporting mRNA translation and their disordered processes that contribute to disease. She founded the Translation Machinery in Health and Disease Gordon Research Conference, an ongoing biannual international conference since 2015. She helped co-found aTyr Pharma, a Nasdaq-listed biotechnology company.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000065427 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031948 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Aug 1996). "Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24". Genomics. 36 (1): 210–3. doi:10.1006/geno.1996.0449. PMID   8812440.
  6. Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Sep 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". The Journal of Biological Chemistry. 272 (36): 22809–16. doi: 10.1074/jbc.272.36.22809 . PMID   9278442.
  7. 1 2 "Entrez Gene: KARS lysyl-tRNA synthetase".
  8. 1 2 Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (Jun 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Molecular Cell. 34 (5): 603–11. doi: 10.1016/j.molcel.2009.05.019 . PMID   19524539.
  9. Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID   14975237.
  10. Lee YN, Razin E (Oct 2005). "Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells". Molecular and Cellular Biology. 25 (20): 8904–12. doi:10.1128/MCB.25.20.8904-8912.2005. PMC   1265770 . PMID   16199869.
  11. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
  12. Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID   9878398.

Further reading