UniProt functional annotation for Q15046



	UniProt functional annotation for Q15046

UniProt code: Q15046.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). {ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:5338216, ECO:0000269|PubMed:9278442}.

Function: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269|PubMed:15220430}.

Catalytic activity: Reaction=ATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl- tRNA(Lys); Xref=Rhea:RHEA:20792, Rhea:RHEA-COMP:9696, Rhea:RHEA- COMP:9697, ChEBI:CHEBI:30616, ChEBI:CHEBI:32551, ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78529, ChEBI:CHEBI:456215; EC=6.1.1.6; Evidence={ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:23159739, ECO:0000269|PubMed:9278442};

Activity regulation: Up-regulated by DARS and EEF1A1, but not by AIMP2. {ECO:0000269|PubMed:18029264}.

Biophysicochemical properties: Kinetic parameters: KM=1.19 uM for tRNA(Lys) {ECO:0000269|PubMed:28887846}; Note=Kcat is 0.31 (sec-1) for aminoacylation for tRNA(Lys). {ECO:0000269|PubMed:28887846};

Subunit: Homodimer and tetradimer (PubMed:18272479, PubMed:23159739, PubMed:26074468, PubMed:28887846). Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464, PubMed:24312579, PubMed:23159739). Interacts with AIMP2 (via N-terminus) and MITF (PubMed:9878398, PubMed:14975237, PubMed:15220430, PubMed:23159739, PubMed:26074468). Interacts with TARSL2 (PubMed:24312579). {ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15220430, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:18272479, ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:23159739, ECO:0000269|PubMed:24312579, ECO:0000269|PubMed:26074468, ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:9878398}.

Subunit: (Microbial infection) Interacts directly with HIV-1 virus GAG protein (PubMed:12756246, PubMed:15220430). {ECO:0000269|PubMed:12756246, ECO:0000269|PubMed:15220430}.

Subcellular location: [Isoform Cytoplasmic]: Cytoplasm, cytosol {ECO:0000269|PubMed:10952987, ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:23159739, ECO:0000269|PubMed:28887846}. Cytoplasm {ECO:0000269|PubMed:15220430}. Nucleus {ECO:0000269|PubMed:15220430, ECO:0000269|PubMed:23159739}. Cell membrane {ECO:0000269|PubMed:15220430}; Peripheral membrane protein {ECO:0000269|PubMed:15220430}. Secreted {ECO:0000269|PubMed:15851690}. Note=Secretion is induced by TNF-alpha (PubMed:15851690). Cytosolic in quiescent mast cells. Translocates into the nucleus in response to mast cell activation by immunoglobulin E (PubMed:23159739). {ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:23159739}.

Subcellular location: [Isoform Mitochondrial]: Mitochondrion {ECO:0000269|PubMed:10952987}.

Domain: The N-terminal domain (1-65) of the cytoplasmic isoform is a functional tRNA-binding domain, 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:0000269|PubMed:15220430, ECO:0000269|PubMed:18029264}.

Ptm: Phosphorylated on a serine residue after mast cell stimulation with immunoglobulin E (IgE). {ECO:0000250|UniProtKB:Q5XIM7}.

Disease: Charcot-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 variants affecting the gene represented in this entry.

Disease: Deafness, 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, ECO:0000269|PubMed:28887846}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Shares a bidirectional promoter with TERF2IP/RAP1. {ECO:0000305|PubMed:14659874}.

Miscellaneous: [Isoform Mitochondrial]: Mitochondrial precursor. Contains a mitochondrial transit peptide at positions 1-16. {ECO:0000305}.

Similarity: Belongs to the class-II aminoacyl-tRNA synthetase family. {ECO:0000305}.

Sequence caution: Sequence=BAA06688.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739). {ECO:0000269\|PubMed:14975237, ECO:0000269\|PubMed:15851690, ECO:0000269\|PubMed:18029264, ECO:0000269\|PubMed:19524539, ECO:0000269\|PubMed:28887846, ECO:0000269\|PubMed:5338216, ECO:0000269\|PubMed:9278442}.



Function:		(Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269\|PubMed:15220430}.


Catalytic activity:		Reaction=ATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl- tRNA(Lys); Xref=Rhea:RHEA:20792, Rhea:RHEA-COMP:9696, Rhea:RHEA- COMP:9697, ChEBI:CHEBI:30616, ChEBI:CHEBI:32551, ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78529, ChEBI:CHEBI:456215; EC=6.1.1.6; Evidence={ECO:0000269\|PubMed:18029264, ECO:0000269\|PubMed:23159739, ECO:0000269\|PubMed:9278442};
Activity regulation:		Up-regulated by DARS and EEF1A1, but not by AIMP2. {ECO:0000269\|PubMed:18029264}.
Biophysicochemical properties:		Kinetic parameters: KM=1.19 uM for tRNA(Lys) {ECO:0000269\|PubMed:28887846}; Note=Kcat is 0.31 (sec-1) for aminoacylation for tRNA(Lys). {ECO:0000269\|PubMed:28887846};
Subunit:		Homodimer and tetradimer (PubMed:18272479, PubMed:23159739, PubMed:26074468, PubMed:28887846). Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464, PubMed:24312579, PubMed:23159739). Interacts with AIMP2 (via N-terminus) and MITF (PubMed:9878398, PubMed:14975237, PubMed:15220430, PubMed:23159739, PubMed:26074468). Interacts with TARSL2 (PubMed:24312579). {ECO:0000269\|PubMed:14975237, ECO:0000269\|PubMed:15220430, ECO:0000269\|PubMed:18029264, ECO:0000269\|PubMed:18272479, ECO:0000269\|PubMed:19131329, ECO:0000269\|PubMed:19289464, ECO:0000269\|PubMed:23159739, ECO:0000269\|PubMed:24312579, ECO:0000269\|PubMed:26074468, ECO:0000269\|PubMed:28887846, ECO:0000269\|PubMed:9878398}.
Subunit:		(Microbial infection) Interacts directly with HIV-1 virus GAG protein (PubMed:12756246, PubMed:15220430). {ECO:0000269\|PubMed:12756246, ECO:0000269\|PubMed:15220430}.
Subcellular location:		[Isoform Cytoplasmic]: Cytoplasm, cytosol {ECO:0000269\|PubMed:10952987, ECO:0000269\|PubMed:19289464, ECO:0000269\|PubMed:23159739, ECO:0000269\|PubMed:28887846}. Cytoplasm {ECO:0000269\|PubMed:15220430}. Nucleus {ECO:0000269\|PubMed:15220430, ECO:0000269\|PubMed:23159739}. Cell membrane {ECO:0000269\|PubMed:15220430}; Peripheral membrane protein {ECO:0000269\|PubMed:15220430}. Secreted {ECO:0000269\|PubMed:15851690}. Note=Secretion is induced by TNF-alpha (PubMed:15851690). Cytosolic in quiescent mast cells. Translocates into the nucleus in response to mast cell activation by immunoglobulin E (PubMed:23159739). {ECO:0000269\|PubMed:15851690, ECO:0000269\|PubMed:23159739}.
Subcellular location:		[Isoform Mitochondrial]: Mitochondrion {ECO:0000269\|PubMed:10952987}.
Domain:		The N-terminal domain (1-65) of the cytoplasmic isoform is a functional tRNA-binding domain, 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:0000269\|PubMed:15220430, ECO:0000269\|PubMed:18029264}.
Ptm:		Phosphorylated on a serine residue after mast cell stimulation with immunoglobulin E (IgE). {ECO:0000250\|UniProtKB:Q5XIM7}.
Disease:		Charcot-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 variants affecting the gene represented in this entry.
Disease:		Deafness, 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, ECO:0000269\|PubMed:28887846}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Shares a bidirectional promoter with TERF2IP/RAP1. {ECO:0000305\|PubMed:14659874}.
Miscellaneous:		[Isoform Mitochondrial]: Mitochondrial precursor. Contains a mitochondrial transit peptide at positions 1-16. {ECO:0000305}.
Similarity:		Belongs to the class-II aminoacyl-tRNA synthetase family. {ECO:0000305}.
Sequence caution:		Sequence=BAA06688.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};