KARS1
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.
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:18029264, PubMed:18272479, PubMed:9278442). 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:14975237, PubMed:19524539, PubMed:23159739, PubMed:5338216).
(Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.
Involvement in disease
Charcot-Marie-Tooth disease, recessive intermediate B
CMTRIB
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Deafness, autosomal recessive, 89
DFNB89
A form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies.
None
The disease is caused by variants affecting the gene represented in this entry.
Deafness, congenital, and adult-onset progressive leukoencephalopathy
DEAPLE
An autosomal recessive, complex neurodegenerative disorder characterized by congenital sensorineural deafness, and progressive motor and cognitive decline apparent in young adulthood. Brain imaging shows diffuse white matter abnormalities affecting various brain regions, consistent with a progressive leukoencephalopathy. More variable additional features may include visual impairment and axonal peripheral neuropathy. Premature death may occurr in some patients.
None
The disease is caused by variants affecting the gene represented in this entry.
Leukoencephalopathy, progressive, infantile-onset, with or without deafness
LEPID
An autosomal recessive, complex neurodegenerative disorder apparent from infancy. LEPID is characterized by early-onset progressive leukoencephalopathy with brainstem and spinal cord calcifications, sensorineural deafness in most patients, global developmental delay with cognitive impairment and poor or absent speech, developmental regression, and neurologic deterioration. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Premature death is common.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on a serine residue after mast cell stimulation with immunoglobulin E (IgE).
Sequence Similarities
Belongs to the class-II aminoacyl-tRNA synthetase family.
Cellular localization
- Isoform Cytoplasmic
- Cytoplasm
- Cytosol
- Cytoplasm
- Nucleus
- Cell membrane
- Peripheral membrane protein
- Secreted
- 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).
- Isoform Mitochondrial
- Mitochondrion
Alternative names
KARS, KIAA0070, KARS1, Lysine--tRNA ligase, Lysyl-tRNA synthetase, LysRS