Serine hydroxymethyltransferase, mitochondrial
Function
Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:25619277, PubMed:29364879, PubMed:33015733). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (PubMed:25619277). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (PubMed:21876188). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29364879, PubMed:29452640). Associates with mitochondrial DNA (PubMed:18063578). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (PubMed:24075985).
Involvement in disease
Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities
NEDCASB
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, moderate to severe intellectual disability, spastic paraparesis, ataxia, and/or peripheral neuropathy. Patients also exhibit dysmorphic features and congenital microcephaly. Most affected individuals develop progressive hypertrophic cardiomyopathy in childhood or have cardiac developmental anomalies. Brain imaging shows corpus callosum abnormalities in all patients, and perisylvian polymicrogyria-like pattern in some individuals.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
One-carbon metabolism; tetrahydrofolate interconversion.
Post-translational modifications
Succinylation at Lys-280 inhibits the hydroxymethyltransferase activity. Desuccinylation by SIRT5 restores the activity, leading to promote cell proliferation.
Sequence Similarities
Belongs to the SHMT family.
Cellular localization
- Mitochondrion
- Mitochondrion matrix
- Mitochondrion nucleoid
- Mitochondrion inner membrane
- Cytoplasm
- Nucleus
- Mainly localizes in the mitochondrion. Also found in the cytoplasm and nucleus as part of the BRISC complex (PubMed:24075985).
Alternative names
SHMT, Glycine hydroxymethyltransferase, Serine methylase, SHMT2