SHMT1

Description

The SHMT1 (serine hydroxymethyltransferase 1) is a protein-coding gene located on chromosome 17.

Serine hydroxymethyltransferase (SHMT) is a pyridoxal phosphate (PLP) (Vitamin B6) dependent enzyme that plays a key role in cellular one-carbon pathways. It catalyzes the reversible conversion of L-serine to glycine and tetrahydrofolate (THF) to 5,10-methylenetetrahydrofolate (5,10-CH2-THF). This reaction is a major source of one-carbon units for the cell.

The structure of the SHMT monomer is similar across prokaryotes and eukaryotes. In prokaryotes, the active enzyme is a dimer, while in eukaryotic cells, it exists as a tetramer. The eukaryotic tetramer resembles two prokaryotic dimers packed together, forming a “dimer of dimers.” The interaction between monomers within a dimer subunit is tighter than the interaction between the two dimers.

Human serine hydroxymethyltransferase 2 (SHMT2) is involved in one-carbon transfer reactions for amino acid and nucleotide metabolism. The switch between dimeric and tetrameric forms of SHMT2, regulated by pyridoxal phosphate, is linked to inflammation. The SHMT2 dimer, but not the PLP-bound tetramer, inhibits the BRISC deubiquitylase complex, suggesting a mechanism for SHMT2 regulation of inflammation.

Each SHMT monomer consists of three domains: an N-terminus “arm,” a “large” domain, and a “small” domain. The N-terminus arm maintains the tight interaction between two monomers. This arm, composed of two alpha helices and a beta sheet, wraps around the other monomer when in oligomeric form.

SHMT1 is also known as CSHMT, SHMT.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing