Serine palmitoyltransferase, long chain base subunit 2, also known as SPTLC2, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''SPTLC2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
SPTLC2 belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Function
''SPTLC2'' encodes a long chain base subunit of
serine palmitoyltransferase
In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction:
:palmitoyl-CoA + L-serine \rightleftharpoons CoA + 3-dehydro-D-sphinganine + CO2
Thus, the two substrates of this enzyme are palmitoyl-CoA ...
(SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. It catalyzes the
pyridoxal 5'-phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ac ...
dependent condensation of L-
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
with an acyl-CoA thioester to yield an amino alcohol. The composition of the SPT complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate.
The SPT complex synthesizes molecules used in various biological processes. For example, sphingosine, an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, can be phosphorylated via sphingosine kinase. The resulting sphingosine-1-phosphate is a potent signaling lipid. Sphingosine is also a substrate for the synthesis of various other molecules including,
ceramides,
sphingomyelin
Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a ethano ...
,
cerebroside
Cerebrosides is the common name for a group of glycosphingolipids called monoglycosylceramides which are important components in animal muscle and nerve cell membranes.
They consist of a ceramide with a single sugar residue at the 1-hydroxyl ...
s and
globosides.
Epidermal ceramides are critical for normal skin barrier function and SPTLC2 is differentially expressed across body sites to regulate epidermal ceramide composition. In particular, SPTLC2 is upregulated in acral granular layer
keratinocytes.
Tissue distribution
SPTLC2 is widely expressed in all tissues.
Clinical significance
Mutations in SPTLC2 were identified in patients with
hereditary sensory neuropathy
Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
They are less common than Charcot-Marie-Tooth disease.
Classif ...
type I.
In response to IL-17A and TNF, SPTLC2 is highly upregulated in
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
and is likely responsible for some of the epidermal ceramide alterations seen in psoriasis plaques.
Alternatively spliced
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...
variants encoding different
isoforms
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...
of SPTLC2 have been identified.
SPTLC2 expression is highly increased at the protein level in brains of patients with
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. No changes are observed at the mRNA level.
References
Further reading
*
*
*
*
*
*
*
*
*
*
*
*
*
{{gene-14-stub