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MGP001698

UniProt Annotations

Entry Information
Gene Namelysyl-tRNA synthetase
Protein EntrySYK_HUMAN
UniProt IDQ15046
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=Cytoplasmic; IsoId=Q15046-1; Sequence=Displayed; Name=Mitochondrial; IsoId=Q15046-2; Sequence=VSP_038481; Note=Mitochondrial precursor. Contains a mitochondrial transit peptide at positions 1-16. Ref.2 (AAG30114) sequence is in conflict in position: 48:R->G. {ECO:0000305};
Catalytic ActivityATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl-tRNA(Lys).
DiseaseCharcot-Marie-Tooth disease, recessive, intermediate type, B (CMTRIB) [MIM:613641]: 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. {ECO:0000269|PubMed:20920668}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDeafness, autosomal recessive, 89 (DFNB89) [MIM:613916]: A form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies. {ECO:0000269|PubMed:23768514}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe 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. {ECO:0000250}.
Enzyme RegulationUp-regulated by DARS and EEF1A1, but not by AIMP2.
FunctionCatalyzes 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. {ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:5338216}.
InteractionQ13155:AIMP2; NbExp=3; IntAct=EBI-356367, EBI-745226; P08865:RPSA; NbExp=5; IntAct=EBI-356367, EBI-354112;
MiscellaneousShares a bidirectional promoter with TERF2IP/RAP1. {ECO:0000305|PubMed:14659874}.
Sequence CautionSequence=BAA06688.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the class-II aminoacyl-tRNA synthetase family. {ECO:0000305}.
Subcellular LocationIsoform Cytoplasmic: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Secreted. Note=Secretion is induced by TNF-alpha.
Subcellular LocationIsoform Mitochondrial: Mitochondrion.
SubunitHomodimer; 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. {ECO:0000269|PubMed:12756246, ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15220430, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:18272479, ECO:0000269|PubMed:9878398}.
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