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Details on Person UniProt:O15269-1 SPTLC1
| Class:Id | ReferenceIsoform:8976783 |
|---|---|
| _chainChangeLog | chain:1-473 added on Fri February 17 2017 |
| _displayName | UniProt:O15269-1 SPTLC1 |
| _timestamp | 2025-02-21 19:01:59 |
| chain | chain:1-473 |
| checksum | BA9E056A869D2EA2 |
| comment | FUNCTION Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity).CATALYTIC ACTIVITY L-serine + hexadecanoyl-CoA + H(+) = 3-oxosphinganine + CO2 + CoACATALYTIC ACTIVITY octadecanoyl-CoA + L-serine + H(+) = 3-oxoeicosasphinganine + CO2 + CoACATALYTIC ACTIVITY tetradecanoyl-CoA + L-serine + H(+) = 3-oxohexadecasphinganine + CO2 + CoACATALYTIC ACTIVITY dodecanoyl-CoA + L-serine + H(+) = 3-oxotetradecasphinganine + CO2 + CoACOFACTOR SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides (PubMed:37308477). This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (Probable).BIOPHYSICOCHEMICAL PROPERTIES Lipid metabolism; sphingolipid metabolism.SUBUNIT Component of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB (PubMed:19132419, PubMed:19416851, PubMed:33558761, PubMed:33558762, PubMed:37308477). The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (PubMed:33558762, PubMed:37308477). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (PubMed:20182505, PubMed:30700557, PubMed:33558762, PubMed:34059824, PubMed:37308477). Forms dimers of heterodimers with SPTLC2 (PubMed:33558761, PubMed:33558762). Interacts with RTN4 (isoform B) (By similarity).INTERACTION Widely expressed. Not detected in small intestine.INDUCTION Expression at protein level is highly increased in brains of patients with Alzheimer disease. No changes are observed at mRNA level.DOMAIN The transmembrane domain is involved in the interaction with ORMDL3.PTM Phosphorylation at Tyr-164 inhibits activity and promotes cell survival.DISEASE The disease is caused by variants affecting the gene represented in this entry. Variants associated with ALS27 tend to disrupt the normal homeostatic regulation of serine palmitoyltransferase (SPT) by ORMDL proteins, resulting in up-regulated SPT activity and elevated levels of canonical SPT products.DISEASE The disease is caused by variants affecting the gene represented in this entry. Variants associated with HSAN1A tend to increase serine palmitoyltransferase (SPT) usage of alanine or glycine rather than serine, resulting in deoxysphingolipid synthesis. Deoxysphingolipids cannot be efficiently degraded by the cell machinery and cause cell toxicity.SIMILARITY Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family. |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: Serine palmitoyltransferase 1 ecNumber evidence="10"2.3.1.50 alternativeName: Long chain base biosynthesis protein 1 shortName: LCB 1 alternativeName: Serine-palmitoyl-CoA transferase 1 shortName: SPT 1 shortName: SPT1 |
| geneName | SPTLC1 LCB1 |
| identifier | O15269 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acyltransferase Alternative splicing Amyotrophic lateral sclerosis Disease variant Endoplasmic reticulum Lipid metabolism Membrane Neurodegeneration Neuropathy Phosphoprotein Proteomics identification Pyridoxal phosphate Reference proteome Sphingolipid metabolism Transferase Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | SPTLC1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990423] ENSEMBL:ENSG00000090054 SPTLC1 [Homo sapiens] |
| secondaryIdentifier | SPTC1_HUMAN A8K681 Q5VWB4 Q96IX6 |
| sequenceLength | 473 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | O15269-1 |
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No pathways have been reviewed or authored by UniProt:O15269-1 SPTLC1 (8976783)
