Description: Homo sapiens lysyl-tRNA synthetase (KARS1), transcript variant 2, mRNA. RefSeq Summary (NM_005548): 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]. Transcript (Including UTRs) Position: hg19 chr16:75,661,622-75,681,585 Size: 19,964 Total Exon Count: 14 Strand: - Coding Region Position: hg19 chr16:75,661,793-75,681,537 Size: 19,745 Coding Exon Count: 14
ID:SYK_HUMAN DESCRIPTION: RecName: Full=Lysine--tRNA ligase; EC=6.1.1.6; AltName: Full=Lysyl-tRNA synthetase; Short=LysRS; 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. CATALYTIC ACTIVITY: ATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl-tRNA(Lys). ENZYME REGULATION: Up-regulated by DARS and EEF1A1, but not by AIMP2. SUBUNIT: Homodimer; also part of a multisubunit complex that groups AIMP1, AIMP2, EEF1A1 and tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro. Interacts with AIMP2 (via N- terminus) and MITF. Interacts directly with HIV-1 virus GAG protein. SUBCELLULAR LOCATION: Isoform Cytoplasmic: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Secreted. Note=Secretion is induced by TNF-alpha. SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion. DOMAIN: The N-terminal domain (1-65) of the cytoplasmic isoform is a functional tRNA-binding domain (By similarity), is required for nuclear localization, is involved in the interaction with DARS, but has a repulsive role in the binding to EEF1A1. A central domain (208-259) is involved in homodimerization and is required for interaction with HIV-1 GAG and incorporation into virions. The C-terminal domain (452-597) is not required for interaction with AIMP2. DISEASE: Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:613641]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. MISCELLANEOUS: Shares a bidirectional promoter with TERF2IP/RAP1 (PubMed:14659874). SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family. SEQUENCE CAUTION: Sequence=BAA06688.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15046
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.