SHMT2
SHMT2 (serine hydroxymethyltransferase 2, also known as mSHMT or SHMT) is the mitochondrial pyridoxal phosphate-dependent enzyme that converts serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate. It supplies one-carbon units for nucleotide biosynthesis and mitochondrial translation. Browse Assay Genie's current range of SHMT2 research reagents below, or read on for the biology behind the target.
SHMT2 catalyses the cleavage of serine to glycine, a reaction that is accompanied by the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis. By transferring one carbon from serine to tetrahydrofolate, it provides the major source of folate one-carbon units in cells. The reaction is reversible, and the enzyme is primarily responsible for glycine synthesis; its activity has been suggested to be the primary source of intracellular glycine.
Within mitochondria, SHMT2 contributes to the de novo mitochondrial thymidylate biosynthesis pathway through its role in glycine and tetrahydrofolate metabolism. Thymidylate synthesis is required to prevent uracil accumulation in mtDNA, and the protein is reported to associate with mitochondrial DNA. SHMT2 is also required for mitochondrial translation: the 5,10-methylenetetrahydrofolate it produces provides methyl donors for the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs.
Beyond its metabolic role, SHMT2 acts as a component of the BRISC complex, where it is required for deubiquitination of IFNAR1. UniProt lists localisation to the mitochondrion (matrix, nucleoid and inner membrane), as well as the cytoplasm and nucleus. The SHMT2 gene encodes the mitochondrial form of the enzyme, while the cytosolic form, SHMT1, is encoded by a gene on chromosome 17. SHMT2 belongs to the SHMT family, and alternative splicing results in multiple transcript variants. The mouse ortholog is Shmt2.
SHMT2 transfers one carbon from serine to tetrahydrofolate, providing the major source of folate one-carbon units in cells.
Its product 5,10-methylenetetrahydrofolate is an essential intermediate for purine biosynthesis and supports mitochondrial thymidylate synthesis.
SHMT2 supports mitochondrial translation by supplying methyl donors for taurinomethyluridine modification of some mitochondrial tRNAs and helps prevent uracil build-up in mtDNA.
As part of the BRISC complex, SHMT2 is required for IFNAR1 deubiquitination, linking metabolism to protein regulation.
SHMT2 catalyses the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate in mitochondria. This provides one-carbon units for purine and thymidylate biosynthesis and for mitochondrial translation. It also functions in the BRISC complex, where it is required for IFNAR1 deubiquitination.
The HGNC name is serine hydroxymethyltransferase 2, previously listed as serine hydroxymethyltransferase 2 (mitochondrial). UniProt names the protein serine hydroxymethyltransferase, mitochondrial, and aliases include mSHMT and SHMT. The enzyme carries the EC number 2.1.2.1. Alternative splicing gives multiple transcript variants.
Both belong to the serine hydroxymethyltransferase family and catalyse the same reaction. SHMT2 encodes the mitochondrial form, while SHMT1 encodes the cytosolic form, located on chromosome 17. SHMT2 activity has been suggested to be the primary source of intracellular glycine. The mouse ortholog of SHMT2 is Shmt2.
The cytosolic counterpart SHMT1 and other one-carbon metabolism targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P34897; product specifications from Assay Genie datasheets.