SARS1
Domain
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
Function
Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:36041817, PubMed:9431993). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:9431993). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423847, PubMed:19423848, PubMed:24940000).
Involvement in disease
Neurodevelopmental disorder with microcephaly, ataxia, and seizures
NEDMAS
An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness.
None
The disease is caused by variants affecting the gene represented in this entry.
A splice site deletion resulting in a five amino acid in-frame insertion in SARS1, is associated with autosomal dominant complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly.
Pathway
Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.
Sequence Similarities
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Tissue Specificity
Brain.
Cellular localization
- Cytoplasm
- Nucleus
- Predominantly cytoplasmic, but a minor proportion is also found in the nucleus.
Alternative names
SARS, SERS, SARS1, Seryl-tRNA synthetase, Seryl-tRNA(Ser/Sec) synthetase, SerRS