GARS1
Function
Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:24898252, PubMed:28675565). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017).
Involvement in disease
Charcot-Marie-Tooth disease, axonal, 2D
CMT2D
A dominant axonal 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. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Neuronopathy, distal hereditary motor, autosomal dominant 5
HMND5
A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
None
The disease is caused by variants affecting the gene represented in this entry.
Spinal muscular atrophy, infantile, James type
SMAJI
An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the class-II aminoacyl-tRNA synthetase family.
Tissue Specificity
Widely expressed, including in brain and spinal cord.
Isoform 2
Expressed in brain, spinal cord, muscle, heart and spleen.
Isoform 1
Expressed in brain, spinal cord, muscle, heart, spleen and liver.
Cellular localization
- Cytoplasm
- Cell projection
- Axon
- Secreted
- Secreted
- Extracellular exosome
- In transfected COS7 cells, not detected in mitochondria, nor in Golgi apparatus (PubMed:17035524). Secreted by motor neuron, possibly through the exosome pathway (By similarity).
- Isoform 1
- Mitochondrion
- Cytoplasm
- Isoform 2
- Cytoplasm
- Cell projection
- Axon
Alternative names
GARS, GARS1, Glycine--tRNA ligase, Diadenosine tetraphosphate synthetase, Glycyl-tRNA synthetase, Glycyl-tRNA synthetase 1, Ap4A synthetase, GlyRS