SPTLC1 explained

Serine palmitoyltransferase, long chain base subunit 1, also known as SPTLC1, is a protein which in humans is encoded by the SPTLC1 gene.^{[1] [2]}

Serine palmitoyltransferase, which consists of two different subunits, is the initial enzyme in sphingolipid biosynthesis. It converts L-serine and palmitoyl CoA to 3-oxosphinganine with pyridoxal 5'-phosphate as a cofactor. The product of this gene is the long chain base subunit 1 of serine palmitoyltransferase. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1, macular disease,^[3] and juvenile amyotrophic lateral sclerosis.^{[4] [5]} Alternatively spliced variants encoding different isoforms have been identified.^[1]

References

Further reading

• Weiss B, Stoffel W . Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis . European Journal of Biochemistry . 249 . 1 . 239–247 . October 1997 . 9363775 . 10.1111/j.1432-1033.1997.00239.x . free .
• Gable K, Slife H, Bacikova D, Monaghan E, Dunn TM . Tsc3p is an 80-amino acid protein associated with serine palmitoyltransferase and required for optimal enzyme activity . The Journal of Biological Chemistry . 275 . 11 . 7597–7603 . March 2000 . 10713067 . 10.1074/jbc.275.11.7597 . free .
• Hanada K, Hara T, Nishijima M . Purification of the serine palmitoyltransferase complex responsible for sphingoid base synthesis by using affinity peptide chromatography techniques . The Journal of Biological Chemistry . 275 . 12 . 8409–8415 . March 2000 . 10722674 . 10.1074/jbc.275.12.8409 . free .
• Perry DK, Carton J, Shah AK, Meredith F, Uhlinger DJ, Hannun YA . Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis . The Journal of Biological Chemistry . 275 . 12 . 9078–9084 . March 2000 . 10722759 . 10.1074/jbc.275.12.9078 . free .
• Bejaoui K, Wu C, Scheffler MD, Haan G, Ashby P, Wu L, de Jong P, Brown RH . 6 . SPTLC1 is mutated in hereditary sensory neuropathy, type 1 . Nature Genetics . 27 . 3 . 261–262 . March 2001 . 11242106 . 10.1038/85817 . 34442339 .
• Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA . Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I . Nature Genetics . 27 . 3 . 309–312 . March 2001 . 11242114 . 10.1038/85879 . 25336349 .
• Nicholson GA, Dawkins JL, Blair IP, Auer-Grumbach M, Brahmbhatt SB, Hulme DJ . Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe . American Journal of Human Genetics . 69 . 3 . 655–659 . September 2001 . 11479835 . 1235494 . 10.1086/323252 .
• Stachowitz S, Alessandrini F, Abeck D, Ring J, Behrendt H . Permeability barrier disruption increases the level of serine palmitoyltransferase in human epidermis . The Journal of Investigative Dermatology . 119 . 5 . 1048–1052 . November 2002 . 12445191 . 10.1046/j.1523-1747.2002.19524.x . free .
• Campbell AM, Hoffman HL . Sensory Radicular Neuropathy Associated with Muscle Wasting in Two Cases . Brain . 87 . 67–74 . March 1964 . 14152213 . 10.1093/brain/87.1.67 .
• Verhoeven K, Coen K, De Vriendt E, Jacobs A, Van Gerwen V, Smouts I, Pou-Serradell A, Martin JJ, Timmerman V, De Jonghe P . 6 . SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I . Neurology . 62 . 6 . 1001–1002 . March 2004 . 15037712 . 10.1212/01.wnl.0000115388.10828.5c . 42500487 .
• Dedov VN, Dedova IV, Nicholson GA . Hypoxia causes aggregation of serine palmitoyltransferase followed by non-apoptotic death of human lymphocytes . Cell Cycle . 3 . 10 . 1271–1277 . October 2004 . 15467453 . 10.4161/cc.3.10.1163 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• McCampbell A, Truong D, Broom DC, Allchorne A, Gable K, Cutler RG, Mattson MP, Woolf CJ, Frosch MP, Harmon JM, Dunn TM, Brown RH . 6 . Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy . Human Molecular Genetics . 14 . 22 . 3507–3521 . November 2005 . 16210380 . 10.1093/hmg/ddi380 . free .
• Chen M, Han G, Dietrich CR, Dunn TM, Cahoon EB . The essential nature of sphingolipids in plants as revealed by the functional identification and characterization of the Arabidopsis LCB1 subunit of serine palmitoyltransferase . The Plant Cell . 18 . 12 . 3576–3593 . December 2006 . 17194770 . 1785403 . 10.1105/tpc.105.040774 .
• Hornemann T, Wei Y, von Eckardstein A . Is the mammalian serine palmitoyltransferase a high-molecular-mass complex? . The Biochemical Journal . 405 . 1 . 157–164 . July 2007 . 17331073 . 1925250 . 10.1042/BJ20070025 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . 6 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

External links

• GeneReviews/NIH/NCBI/UW entry on Hereditary Sensory Neuropathy Type I

Notes and References

1. Web site: Entrez Gene: SPTLC1 serine palmitoyltransferase, long chain base subunit 1.
2. Weiss B, Stoffel W . Human and murine serine-palmitoyl-CoA transferase--cloning, expression and characterization of the key enzyme in sphingolipid synthesis . European Journal of Biochemistry . 249 . 1 . 239–247 . October 1997 . 9363775 . 10.1111/j.1432-1033.1997.00239.x . free .
3. Gantner ML, Eade K, Wallace M, Handzlik MK, Fallon R, Trombley J, Bonelli R, Giles S, Harkins-Perry S, Heeren TF, Sauer L, Ideguchi Y, Baldini M, Scheppke L, Dorrell MI, Kitano M, Hart BJ, Cai C, Nagasaki T, Badur MG, Okada M, Woods SM, Egan C, Gillies M, Guymer R, Eichler F, Bahlo M, Fruttiger M, Allikmets R, Bernstein PS, Metallo CM, Friedlander M . 6 . Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy . The New England Journal of Medicine . 381 . 15 . 1422–1433 . October 2019 . 31509666 . 7685488 . 10.1056/NEJMoa1815111 .
4. Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, etak . Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis . JAMA Neurology . 78 . 10 . 1236–1248 . October 2021 . 34459874 . 8406220 . 10.1001/jamaneurol.2021.2598 .
5. Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JA, Moreira AL, Kok F, Introna A, Logroscino G, Grunseich C, Nickolls AR, Pourshafie N, Neuhaus SB, Saade D, Gangfuß A, Kölbel H, Piccus Z, Le Pichon CE, Fiorillo C, Ly CV, Töpf A, Brady L, Specht S, Zidell A, Pedro H, Mittelmann E, Thomas FP, Chao KR, Konersman CG, Cho MT, Brandt T, Straub V, Connolly AM, Schara U, Roos A, Tarnopolsky M, Höke A, Brown RH, Lee CH, Hornemann T, Dunn TM, Bönnemann CG . 6 . Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis . Nature Medicine . 27 . 7 . 1197–1204 . July 2021 . 34059824 . 9309980 . 10.1038/s41591-021-01346-1 .