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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yiu OCA], [https://pdbe.org/7yiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yiu RCSB], [https://www.ebi.ac.uk/pdbsum/7yiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yiu ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yiu OCA], [https://pdbe.org/7yiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yiu RCSB], [https://www.ebi.ac.uk/pdbsum/7yiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yiu ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
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| [https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Hereditary sensory and autonomic neuropathy type 1. The disease is caused by variants affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (PubMed:23658386).<ref>PMID:23658386</ref> <ref>PMID:26573920</ref>
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| == Function ==
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| [https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (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. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref>
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| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.
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| Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.,Xie T, Liu P, Wu X, Dong F, Zhang Z, Yue J, Mahawar U, Farooq F, Vohra H, Fang Q, Liu W, Wattenberg BW, Gong X Nat Commun. 2023 Jun 13;14(1):3475. doi: 10.1038/s41467-023-39274-y. PMID:37308477<ref>PMID:37308477</ref>
| | ==See Also== |
| | | *[[Serine palmitoyltransferase 3D structures|Serine palmitoyltransferase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 7yiu" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
