SPTLC2

Description

The SPTLC2 (serine palmitoyltransferase long chain base subunit 2) is a protein-coding gene located on chromosome 14.

SPTLC2, also known as Serine palmitoyltransferase, long chain base subunit 2, is a protein encoded by the SPTLC2 gene in humans. It belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. SPTLC2 is a subunit of the serine palmitoyltransferase (SPT) enzyme, which is a heterodimer formed with LCB1/SPTLC1. This complex serves as the catalytic core of the enzyme, responsible for catalyzing the condensation of L-serine with an acyl-CoA thioester. This reaction, which is dependent on pyridoxal 5'-phosphate, produces an amino alcohol. The specific composition of the SPT complex determines its substrate preference. For instance, the SPTLC1-SPTLC2-SPTSSA complex exhibits a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex shows a preference for C18-CoA substrate. The SPT complex synthesizes molecules crucial for various biological processes, including sphingosine, an 18-carbon amino alcohol with an unsaturated hydrocarbon chain. Sphingosine can be phosphorylated via sphingosine kinase to form sphingosine-1-phosphate, a potent signaling lipid.

SPTLC2 is a subunit of the serine palmitoyltransferase (SPT) enzyme complex, which is essential for the initial and rate-limiting step in sphingolipid biosynthesis. SPT catalyzes the condensation of L-serine and activated acyl-CoA, primarily palmitoyl-CoA, to form long-chain bases. The SPT complex consists of SPTLC1, either SPTLC2 or SPTLC3, and either SPTSSA or SPTSSB. The heterodimer of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while the SPTSSA or SPTSSB subunits determine substrate specificity. SPTLC1-SPTLC2-SPTSSA displays a strong preference for C16-CoA, whereas SPTLC1-SPTLC3-SPTSSA utilizes both C14-CoA and C16-CoA, favoring C14-CoA slightly. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA, while SPTLC1-SPTLC3-SPTSSB utilizes a broader range of acyl-CoAs without a clear preference. SPTLC2 is crucial for adipogenesis and interacts with ORMDL proteins, particularly ORMDL3, which negatively regulate SPT activity in the presence of ceramides.

SPTLC2 is also known as HSN1C, LCB2, LCB2A, NSAN1C, SPT2, hLCB2a.

Associated Diseases

• Hereditary sensory and autonomic neuropathy type 1
• Neuropathy, hereditary sensory and autonomic, type IC