SHMT2

This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants.

serine hydroxymethyltransferase 2 (mitochondrial)

Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (PubMed:24075985, PubMed:29364879, PubMed:33015733 PubMed:25619277, 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:29452640, PubMed:29364879).
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).

Biological Process folic acid metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process glycine biosynthetic process from serineManual Assertion Based On ExperimentIBA:GO_Central
Biological Process glycine metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process L-serine biosynthetic processIEA:Ensembl
Biological Process L-serine catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process L-serine metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process one-carbon metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of cell population proliferationIEA:Ensembl
Biological Process protein homotetramerizationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein K63-linked deubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein tetramerizationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process purine nucleobase biosynthetic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of aerobic respirationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of mitochondrial translationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of oxidative phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process response to type I interferonManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process tetrahydrofolate interconversionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process tetrahydrofolate metabolic processManual Assertion Based On ExperimentIDA:UniProtKB

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).

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.

Succinylation at Lys-280 inhibits the hydroxymethyltransferase activity. Desuccinylation by SIRT5 restores the activity, leading to promote cell proliferation.