YARS1
Domain
The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.
Function
Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949).
Involvement in disease
Charcot-Marie-Tooth disease, dominant intermediate C
CMTDIC
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. The dominant intermediate type C is 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.
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2
IMNEPD2
An autosomal recessive disorder with variable clinical manifestations and severity. Main features include cholestatic hepatitis, poor feeding, poor overall growth, and hypoglycemia apparent from infancy. Most patients have variable global developmental delay, sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Death in early childhood may occur.
None
The disease is caused by variants affecting the gene represented in this entry.
Defects in YARS1 may be the cause of proximal-predominant motor neuropathy. Affected individuals may develop tremors, cramping of hands, asymmetric weakness in the upper and lower extremities, and present with elevated creatine kinase levels.
Sequence Similarities
Belongs to the class-I aminoacyl-tRNA synthetase family.
Cellular localization
- Cytoplasm
- Nucleus
- Cytoplasmic in normal conditions (PubMed:25533949). Resveratrol-binding in response to serum starvation promotes relocalization to the nucleus (PubMed:25533949).
Alternative names
YARS, YARS1, Tyrosyl-tRNA synthetase, TyrRS