Literature summary for 2.3.1.50 extracted from

Bode, H.; Bourquin, F.; Suriyanarayanan, S.; Wei, Y.; Alecu, I.; Othman, A.; Von Eckardstein, A.; Hornemann, T.
HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship (2016), Hum. Mol. Genet., 25, 853-865.

Search for more literature for 2.3.1.50

Cloned(Commentary)

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

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/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	O15269 and O15270	subunits SPTLC1 (O15269) and SPTLC2(O15270); subunits SPTLC1 and SPTLC2	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Subunits	Comment	Organism
heterodimer	the membrane-bound heterodimer composed of two subunits SPTLC1 and SPTLC2	Homo sapiens

Synonyms

Synonyms	Comment	Organism
serine palmitoyltransferase	-	Homo sapiens
SPT	-	Homo sapiens

General Information

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

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Release 2023.1 (January 2023)