Cloned (Comment) | Organism |
---|---|
expression of wild-type and mutant enzymes in HEK-293 cells. The overexpression of wild-type subunit SPTLC1 does not increase SPT enzyme activity compared with controls (empty vector), whereas overexpressing subunit SPTLC2 results in a 2fold increase in enzyme activity | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
A182P | naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
C133W | naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, the mutant shows showa a significantly increased canonical activity and is associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
C133Y | naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, the mutant shows showa a significantly increased canonical activity and is associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
G246R | expression of mutant G246R in in LYB cells, which is the same mutation that is present in LYB endogenously, neither restores canonical activity nor results in the formation of 1-deoxy-sphingolipids | Homo sapiens |
G382V | naturally occuring mutation in subunit LCB2 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
I504F | naturally occuring mutation in subunit LCB2 involved in hereditary sensory and autonomic neuropathy type I disease, the mutant shows showa a significantly increased canonical activity and is associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
I505Y | naturally occuring mutation in subunit LCB2 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids. The mutant shows an increased canonical activity and increased formation of C20 sphingoid base, associated with an exceptionally severe HSAN1 phenotype, where C20 sphingosine levels are also confirmed in plasma of patients | Homo sapiens |
additional information | mutations associated with the mild form cluster around the active site, whereas mutations associated with the severe form are located on the surface of the enzyme protein. Overview of clinical features of HSAN1 patients with SPTLC1 mutations, genotype-phenotype association in HSAN1 | Homo sapiens |
S331F | naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids. The mutant shows an increased canonical activity and increased formation of C20 sphingoid base, associated with an exceptionally severe HSAN1 phenotype, where C20 sphingosine levels are also confirmed in plasma of patients. Expression of the p.S331F mutant in enzyme-deficient LYB cells fully restores canonical activity, and activity is even 9-10fold higher compared with the wild-type subunit | Homo sapiens |
S331Y | naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids.The mutant shows an increased canonical activity and increased formation of C20 sphingoid base, associated with an exceptionally severe HSAN1 phenotype, where C20 sphingosine levels are also confirmed in plasma of patients | Homo sapiens |
S384F | naturally occuring mutation in subunit LCB2 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
palmitoyl-CoA + L-serine | Homo sapiens | - |
CoA + 3-dehydro-D-sphinganine + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O15269 and O15270 | subunits SPTLC1 (O15269) and SPTLC2(O15270); subunits SPTLC1 and SPTLC2 | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
palmitoyl-CoA + L-alanine | low activity with the wild-type enzyme, but increased activity with some mutants of the enzyme, overview | Homo sapiens | CoA + (2S)-2-aminooctadecan-3-one + CO2 | - |
? | |
palmitoyl-CoA + L-serine | - |
Homo sapiens | CoA + 3-dehydro-D-sphinganine + CO2 | - |
? |
Subunits | Comment | Organism |
---|---|---|
heterodimer | the membrane-bound heterodimer composed of two subunits SPTLC1 and SPTLC2 | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
serine palmitoyltransferase | - |
Homo sapiens |
SPT | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare autosomal dominant inherited peripheral neuropathy caused by mutations in the SPTLC1 and SPTLC2 subunits of serine palmitoyltransferase. The mutations induce a permanent shift in the substrate preference from L-serine to L-alanine, which results in the pathological formation of atypical and neurotoxic 1-deoxy-sphingolipids. Overview of clinical features of HSAN1 patients with SPTLC1 mutations, genotype-phenotype association in HSAN1 | Homo sapiens |
additional information | wild-type and mutant enzyme structure homology modeling and structure-function analyses, overview | Homo sapiens |