ID SPTC1_HUMAN Reviewed; 473 AA. AC O15269; A8K681; Q5VWB4; Q96IX6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Serine palmitoyltransferase 1; DE EC=2.3.1.50 {ECO:0000269|PubMed:19416851}; DE AltName: Full=Long chain base biosynthesis protein 1; DE Short=LCB 1; DE AltName: Full=Serine-palmitoyl-CoA transferase 1; DE Short=SPT 1; DE Short=SPT1; GN Name=SPTLC1; Synonyms=LCB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=9363775; DOI=10.1111/j.1432-1033.1997.00239.x; RA Weiss B., Stoffel W.; RT "Human and murine serine-palmitoyl-CoA transferase. Cloning, expression and RT characterization of the key enzyme in sphingolipid synthesis."; RL Eur. J. Biochem. 249:239-247(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANTS HSAN1A RP TRP-133; TYR-133 AND ASP-144. RX PubMed=11242114; DOI=10.1038/85879; RA Dawkins J.L., Hulme D.J., Brahmbhatt S.B., Auer-Grumbach M., RA Nicholson G.A.; RT "Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base RT subunit-1, cause hereditary sensory neuropathy type I."; RL Nat. Genet. 27:309-312(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP TISSUE SPECIFICITY. RX PubMed=17023427; DOI=10.1074/jbc.m608066200; RA Hornemann T., Richard S., Ruetti M.F., Wei Y., von Eckardstein A.; RT "Cloning and initial characterization of a new subunit for mammalian RT serine-palmitoyltransferase."; RL J. Biol. Chem. 281:37275-37281(2006). RN [8] RP FUNCTION. RX PubMed=19648650; DOI=10.1074/jbc.m109.023192; RA Hornemann T., Penno A., Ruetti M.F., Ernst D., Kivrak-Pfiffner F., RA Rohrer L., von Eckardstein A.; RT "The SPTLC3 subunit of serine palmitoyltransferase generates short chain RT sphingoid bases."; RL J. Biol. Chem. 284:26322-26330(2009). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION IN THE SPT COMPLEX, AND RP INTERACTION WITH SPTSSA AND SPTSSB. RX PubMed=19416851; DOI=10.1073/pnas.0811269106; RA Han G., Gupta S.D., Gable K., Niranjanakumari S., Moitra P., Eichler F., RA Brown R.H. Jr., Harmon J.M., Dunn T.M.; RT "Identification of small subunits of mammalian serine palmitoyltransferase RT that confer distinct acyl-CoA substrate specificities."; RL Proc. Natl. Acad. Sci. U.S.A. 106:8186-8191(2009). RN [10] RP BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF VARIANT HSAN1A RP TRP-133. RX PubMed=20504773; DOI=10.1074/jbc.m110.122259; RA Gable K., Gupta S.D., Han G., Niranjanakumari S., Harmon J.M., Dunn T.M.; RT "A disease-causing mutation in the active site of serine RT palmitoyltransferase causes catalytic promiscuity."; RL J. Biol. Chem. 285:22846-22852(2010). RN [11] RP INTERACTION WITH ORMDL3. RX PubMed=20182505; DOI=10.1038/nature08787; RA Breslow D.K., Collins S.R., Bodenmiller B., Aebersold R., Simons K., RA Shevchenko A., Ejsing C.S., Weissman J.S.; RT "Orm family proteins mediate sphingolipid homeostasis."; RL Nature 463:1048-1053(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP INDUCTION IN ALZHEIMER DISEASE. RX PubMed=21994399; DOI=10.1523/jneurosci.3883-11.2011; RA Geekiyanage H., Chan C.; RT "MicroRNA-137/181c regulates serine palmitoyltransferase and in turn RT amyloid beta, novel targets in sporadic Alzheimer's disease."; RL J. Neurosci. 31:14820-14830(2011). RN [14] RP PHOSPHORYLATION AT TYR-164, AND MUTAGENESIS OF TYR-164. RX PubMed=23629659; DOI=10.1074/jbc.m112.409185; RA Taouji S., Higa A., Delom F., Palcy S., Mahon F.X., Pasquet J.M., Bosse R., RA Segui B., Chevet E.; RT "Phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on RT tyrosine 164 inhibits its activity and promotes cell survival."; RL J. Biol. Chem. 288:17190-17201(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [16] RP REGULATION OF SPT COMPLEX ACTIVITY BY ORMDL PROTEINS IN THE PRESENCE OF RP CERAMIDES. RX PubMed=30700557; DOI=10.1074/jbc.ra118.007291; RA Davis D.L., Gable K., Suemitsu J., Dunn T.M., Wattenberg B.W.; RT "The ORMDL/Orm-serine palmitoyltransferase (SPT) complex is directly RT regulated by ceramide: Reconstitution of SPT regulation in isolated RT membranes."; RL J. Biol. Chem. 294:5146-5156(2019). RN [17] {ECO:0007744|PDB:7K0I, ECO:0007744|PDB:7K0J, ECO:0007744|PDB:7K0K, ECO:0007744|PDB:7K0L, ECO:0007744|PDB:7K0M, ECO:0007744|PDB:7K0N, ECO:0007744|PDB:7K0O, ECO:0007744|PDB:7K0P, ECO:0007744|PDB:7K0Q} RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH SPTLC2; RP SPTSSA AND ORMDL3, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=33558761; DOI=10.1038/s41594-020-00551-9; RA Wang Y., Niu Y., Zhang Z., Gable K., Gupta S.D., Somashekarappa N., Han G., RA Zhao H., Myasnikov A.G., Kalathur R.C., Dunn T.M., Lee C.H.; RT "Structural insights into the regulation of human serine RT palmitoyltransferase complexes."; RL Nat. Struct. Mol. Biol. 28:240-248(2021). RN [18] {ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK} RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SPTLC2; RP SPTSSA AND ORMDL3, FUNCTION, AND MUTAGENESIS OF PHE-138; PHE-337 AND RP SER-338. RX PubMed=33558762; DOI=10.1038/s41594-020-00553-7; RA Li S., Xie T., Liu P., Wang L., Gong X.; RT "Structural insights into the assembly and substrate selectivity of human RT SPT-ORMDL3 complex."; RL Nat. Struct. Mol. Biol. 28:249-257(2021). RN [19] {ECO:0007744|PDB:7YIU, ECO:0007744|PDB:7YIY, ECO:0007744|PDB:7YJ1, ECO:0007744|PDB:7YJ2} RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) IN COMPLEX WITH SPTLC2; RP SPTSSA AND ORMDL3, CHARACTERIZATION OF VARIANTS ALS27 PHE-23; LEU-39 DEL RP AND 40-PHE-SER-41 DEL, AND ACTIVITY REGULATION. RX PubMed=37308477; DOI=10.1038/s41467-023-39274-y; RA Xie T., Liu P., Wu X., Dong F., Zhang Z., Yue J., Mahawar U., Farooq F., RA Vohra H., Fang Q., Liu W., Wattenberg B.W., Gong X.; RT "Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid RT homeostasis."; RL Nat. Commun. 14:3475-3475(2023). RN [20] RP VARIANT ALA-387. RX PubMed=15037712; DOI=10.1212/01.wnl.0000115388.10828.5c; RA Verhoeven K., Coen K., De Vriendt E., Jacobs A., Van Gerwen V., Smouts I., RA Pou-Serradell A., Martin J.-J., Timmerman V., De Jonghe P.; RT "SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type RT I."; RL Neurology 62:1001-1002(2004). RN [21] RP VARIANT LEU-151. RX PubMed=17060578; DOI=10.1212/01.wnl.0000240068.21499.f5; RA Meggouh F., Bienfait H.M.E., Weterman M.A.J., de Visser M., Baas F.; RT "Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene."; RL Neurology 67:1476-1478(2006). RN [22] RP VARIANT [LARGE SCALE ANALYSIS] TRP-239. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [23] RP VARIANTS HSAN1A PHE-331 AND VAL-352, AND VARIANT ALA-387. RX PubMed=19651702; DOI=10.1093/brain/awp198; RA Rotthier A., Baets J., De Vriendt E., Jacobs A., Auer-Grumbach M., Levy N., RA Bonello-Palot N., Kilic S.S., Weis J., Nascimento A., Swinkels M., RA Kruyt M.C., Jordanova A., De Jonghe P., Timmerman V.; RT "Genes for hereditary sensory and autonomic neuropathies: a genotype- RT phenotype correlation."; RL Brain 132:2699-2711(2009). RN [24] RP CHARACTERIZATION OF VARIANTS HSAN1A TYR-133; TRP-133 AND ASP-144, RP CHARACTERIZATION OF VARIANT ALA-387, LACK OF ASSOCIATION OF VARIANT ALA-387 RP WITH HSAN1A, AND INTERACTION WITH SPTLC2. RX PubMed=19132419; DOI=10.1007/s10048-008-0168-7; RA Hornemann T., Penno A., Richard S., Nicholson G., van Dijk F.S., RA Rotthier A., Timmerman V., von Eckardstein A.; RT "A systematic comparison of all mutations in hereditary sensory neuropathy RT type I (HSAN I) reveals that the G387A mutation is not disease RT associated."; RL Neurogenetics 10:135-143(2009). RN [25] RP VARIANT HSAN1A PHE-331, CHARACTERIZATION OF VARIANTS HSAN1A TRP-133; RP PHE-331 AND VAL-352, AND SUBCELLULAR LOCATION. RX PubMed=21618344; DOI=10.1002/humu.21481; RA Rotthier A., Penno A., Rautenstrauss B., Auer-Grumbach M., Stettner G.M., RA Asselbergh B., Van Hoof K., Sticht H., Levy N., Timmerman V., Hornemann T., RA Janssens K.; RT "Characterization of two mutations in the SPTLC1 subunit of serine RT palmitoyltransferase associated with hereditary sensory and autonomic RT neuropathy type I."; RL Hum. Mutat. 32:E2211-E2225(2011). RN [26] RP VARIANT HSAN1A TRP-133, AND VARIANT GLY-310. RX PubMed=22302274; DOI=10.1007/s00415-011-6397-y; RA Davidson G.L., Murphy S.M., Polke J.M., Laura M., Salih M.A., Muntoni F., RA Blake J., Brandner S., Davies N., Horvath R., Price S., Donaghy M., RA Roberts M., Foulds N., Ramdharry G., Soler D., Lunn M.P., Manji H., RA Davis M.B., Houlden H., Reilly M.M.; RT "Frequency of mutations in the genes associated with hereditary sensory and RT autonomic neuropathy in a UK cohort."; RL J. Neurol. 259:1673-1685(2012). RN [27] RP INVOLVEMENT IN HSAN1A, VARIANT HSAN1A TYR-331, AND CHARACTERIZATION OF RP VARIANT HSAN1A TYR-331. RX PubMed=23454272; DOI=10.1016/j.ejmg.2013.02.002; RA Auer-Grumbach M., Bode H., Pieber T.R., Schabhuettl M., Fischer D., RA Seidl R., Graf E., Wieland T., Schuh R., Vacariu G., Grill F., RA Timmerman V., Strom T.M., Hornemann T.; RT "Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a RT distinct syndromic phenotype."; RL Eur. J. Med. Genet. 56:266-269(2013). RN [28] RP VARIANT HSAN1A PHE-331. RX PubMed=24247255; DOI=10.3892/mmr.2013.1808; RA Suh B.C., Hong Y.B., Nakhro K., Nam S.H., Chung K.W., Choi B.O.; RT "Early-onset severe hereditary sensory and autonomic neuropathy type 1 with RT S331F SPTLC1 mutation."; RL Mol. Med. Report. 9:481-486(2014). RN [29] RP VARIANT HSAN1A ASP-144. RX PubMed=30420926; DOI=10.1155/2018/1898151; RA Ho K.W.D., Jerath N.U.; RT "V144D Mutation of SPTLC1 Can Present with Both Painful and Painless RT Phenotypes in Hereditary Sensory and Autonomic Neuropathies Type I."; RL Case Rep. Genet. 2018:1898151-1898151(2018). RN [30] RP INVOLVEMENT IN ALS27, AND VARIANTS ALS27 SER-20; LEU-39 DEL AND TYR-331. RX PubMed=34459874; DOI=10.1001/jamaneurol.2021.2598; RG FALS Sequencing Consortium; RG American Genome Center; RG International ALS Genomics Consortium; RG and ITALSGEN Consortium; RA Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., RA Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., RA Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., RA Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., RA Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., RA Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H. Jr., Calvo A., Mora G., RA Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., RA Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., RA Smith B.N., Traynor B.J., Smith B.N., Ticozzi N., Fallini C., Gkazi A.S., RA Topp S.D., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., RA Troakes C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., RA Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., RA Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., RA Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., RA van Rheenen W., Rademakers R., van Blitterswijk M., Lauria G., Duga S., RA Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., RA Blair I.P., Leblond-Manry C., Rouleau G.A., Hardiman O., Morrison K.E., RA Veldink J.H., van den Berg L.H., Al-Chalabi A., Pall H., Shaw P.J., RA Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., RA Gellera C., Ratti A., Brown R.H. Jr., Silani V., Shaw C.E., Landers J.E., RA Dalgard C.L., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., RA Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., RA Abramzon Y., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., RA Brice A., Broach J., Campbell R.H., Camu W., Chia R., Cooper-Knock J., RA Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., RA Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., RA Gibbs J.R., Gibson S.B., Glass J.D., Hardy J., Harms M.B., RA Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., RA Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., RA MacGowan D.J.L., Maragakis N.J., Mora G., Mouzat K., Murphy N.A., RA Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., RA Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., RA Ravits J.M., Renton A.E., Rivera A., Robberecht W., Rogaeva E., RA Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Shaw P.J., RA Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Tienari P.J., RA Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., RA Zinman L., Landers J.E., Chio A., Traynor B.J., Angelocola S.M., RA Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., RA Bisogni G., Borghero G., Brunetti M., Cabona C., Calvo A., Canale F., RA Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., RA Carrera P., Casale F., Chio A., Colletti T., Conforti F.L., Conte A., RA Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., DeMarco G., RA Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., RA Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., RA Iazzolino B., Introna A., La Bella V., Lattante S., Lauria G., Liguori R., RA Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., RA Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., RA Martinelli I., Messina S., Moglia C., Mora G., Mosca L., Murru M.R., RA Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., RA Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., RA Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., RA Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., RA Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., RA Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E.; RT "Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic RT Lateral Sclerosis."; RL JAMA Neurol. 78:1236-1248(2021). RN [31] RP INVOLVEMENT IN ALS27, VARIANTS ALS27 SER-20; PHE-23; LEU-39 DEL AND RP 40-PHE-SER-41 DEL, CHARACTERIZATION OF VARIANTS ALS27 SER-20; PHE-23; RP LEU-39 DEL AND 40-PHE-SER-41 DEL, AND HOMEOSTATIC REGULATION BY ORMDL3 IN RP THE PRESENCE OF CERAMIDES. RX PubMed=34059824; DOI=10.1038/s41591-021-01346-1; RA Mohassel P., Donkervoort S., Lone M.A., Nalls M., Gable K., Gupta S.D., RA Foley A.R., Hu Y., Saute J.A.M., Moreira A.L., Kok F., Introna A., RA Logroscino G., Grunseich C., Nickolls A.R., Pourshafie N., Neuhaus S.B., RA Saade D., Gangfuss A., Koelbel H., Piccus Z., Le Pichon C.E., Fiorillo C., RA Ly C.V., Toepf A., Brady L., Specht S., Zidell A., Pedro H., Mittelmann E., RA Thomas F.P., Chao K.R., Konersman C.G., Cho M.T., Brandt T., Straub V., RA Connolly A.M., Schara U., Roos A., Tarnopolsky M., Hoeke A., Brown R.H., RA Lee C.H., Hornemann T., Dunn T.M., Boennemann C.G.; RT "Childhood amyotrophic lateral sclerosis caused by excess sphingolipid RT synthesis."; RL Nat. Med. 27:1197-1204(2021). RN [32] RP INVOLVEMENT IN ALS27, AND VARIANT ALS27 ARG-38. RX PubMed=36204986; DOI=10.1080/21678421.2022.2096409; RA Liu X., He J., Yu W., Fan D.; RT "A de novo c.113 T > C: p.L38R mutation of SPTLC1: case report of a girl RT with sporadic juvenile amyotrophic lateral sclerosis."; RL Amyotroph. Lateral Scler. Frontotemporal Degener. 23:634-637(2022). CC -!- FUNCTION: Component of the serine palmitoyltransferase multisubunit CC enzyme (SPT) that catalyzes the initial and rate-limiting step in CC sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA CC (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex CC is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this CC complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core CC (PubMed:19416851, PubMed:33558762). The composition of the serine CC palmitoyltransferase (SPT) complex determines the substrate preference CC (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex CC shows a strong preference for C16-CoA substrate, while the SPTLC1- CC SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with CC a slight preference for C14-CoA (PubMed:19648650, PubMed:19416851). The CC SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA CC substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability CC to use a broader range of acyl-CoAs, without apparent preference CC (PubMed:19648650, PubMed:19416851, PubMed:33558761, PubMed:33558762). CC Required for adipocyte cell viability and metabolic homeostasis (By CC similarity). {ECO:0000250|UniProtKB:O35704, CC ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:19648650, CC ECO:0000269|PubMed:33558761, ECO:0000269|PubMed:33558762}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hexadecanoyl-CoA + L-serine = 3-oxosphinganine + CO2 + CC CoA; Xref=Rhea:RHEA:14761, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, CC ChEBI:CHEBI:58299; EC=2.3.1.50; CC Evidence={ECO:0000269|PubMed:19416851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14762; CC Evidence={ECO:0000269|PubMed:19416851}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + L-serine + octadecanoyl-CoA = 3-oxoeicosasphinganine + CC CO2 + CoA; Xref=Rhea:RHEA:33683, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57394, ChEBI:CHEBI:65073; CC Evidence={ECO:0000269|PubMed:19416851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33684; CC Evidence={ECO:0000269|PubMed:19416851}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + L-serine + tetradecanoyl-CoA = 3-oxohexadecasphinganine CC + CO2 + CoA; Xref=Rhea:RHEA:35675, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57385, ChEBI:CHEBI:71007; CC Evidence={ECO:0000269|PubMed:19416851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35676; CC Evidence={ECO:0000269|PubMed:19416851}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dodecanoyl-CoA + H(+) + L-serine = 3-oxotetradecasphinganine + CC CO2 + CoA; Xref=Rhea:RHEA:35679, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57375, ChEBI:CHEBI:71008; CC Evidence={ECO:0000269|PubMed:19416851}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35680; CC Evidence={ECO:0000269|PubMed:19416851}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: SPT complex catalytic activity is negatively CC regulated by ORMDL proteins, including ORMDL3, in the presence of CC ceramides (PubMed:37308477). This mechanism allows to maintain ceramide CC levels at sufficient concentrations for the production of complex CC sphingolipids, but which prevents the accumulation of ceramides to CC levels that trigger apoptosis (Probable). {ECO:0000269|PubMed:37308477, CC ECO:0000305}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.75 mM for L-serine {ECO:0000269|PubMed:20504773}; CC KM=0.3 mM for L-serine {ECO:0000269|PubMed:33558761}; CC Vmax=1350 pmol/min/mg enzyme {ECO:0000269|PubMed:20504773}; CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism. CC {ECO:0000269|PubMed:19416851}. CC -!- SUBUNIT: Component of the serine palmitoyltransferase (SPT) complex, CC which is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB CC (PubMed:19416851, PubMed:33558761, PubMed:33558762, PubMed:37308477, CC PubMed:19132419). The heterodimer consisting of SPTLC1 and CC SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or CC SPTSSB subunits determine substrate specificity (PubMed:33558762, CC PubMed:37308477). SPT also interacts with ORMDL proteins, especially CC ORMDL3, which negatively regulate SPT activity in the presence of CC ceramides (PubMed:20182505, PubMed:30700557, PubMed:33558762, CC PubMed:37308477, PubMed:34059824). Forms dimers of heterodimers with CC SPTLC2 (PubMed:33558761, PubMed:33558762). Interacts with RTN4 (isoform CC B) (By similarity). {ECO:0000250|UniProtKB:O35704, CC ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:19416851, CC ECO:0000269|PubMed:20182505, ECO:0000269|PubMed:30700557, CC ECO:0000269|PubMed:33558761, ECO:0000269|PubMed:33558762, CC ECO:0000269|PubMed:34059824, ECO:0000269|PubMed:37308477}. CC -!- INTERACTION: CC O15269; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-1044323, EBI-721750; CC O15269; Q9NUV7: SPTLC3; NbExp=3; IntAct=EBI-1044323, EBI-11614219; CC O15269-2; Q86SG2: ANKRD23; NbExp=3; IntAct=EBI-25912901, EBI-5661893; CC O15269-2; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-25912901, EBI-12891828; CC O15269-2; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-25912901, EBI-2822550; CC O15269-2; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-25912901, EBI-3942425; CC O15269-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-25912901, EBI-357085; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:21618344}; Single-pass membrane protein CC {ECO:0000250|UniProtKB:O35704}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15269-1; Sequence=Displayed; CC Name=2; CC IsoId=O15269-2; Sequence=VSP_043127, VSP_043128; CC -!- TISSUE SPECIFICITY: Widely expressed. Not detected in small intestine. CC {ECO:0000269|PubMed:17023427}. CC -!- INDUCTION: Expression at protein level is highly increased in brains of CC patients with Alzheimer disease. No changes are observed at mRNA level. CC {ECO:0000269|PubMed:21994399}. CC -!- DOMAIN: The transmembrane domain is involved in the interaction with CC ORMDL3. {ECO:0000269|PubMed:33558762}. CC -!- PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell CC survival. {ECO:0000269|PubMed:23629659}. CC -!- DISEASE: Amyotrophic lateral sclerosis 27, juvenile (ALS27) CC [MIM:620285]: A form of amyotrophic lateral sclerosis, a CC neurodegenerative disorder affecting upper motor neurons in the brain CC and lower motor neurons in the brain stem and spinal cord, resulting in CC fatal paralysis. Sensory abnormalities are absent. The pathologic CC hallmarks of the disease include pallor of the corticospinal tract due CC to loss of motor neurons, presence of ubiquitin-positive inclusions CC within surviving motor neurons, and deposition of pathologic CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to CC be multifactorial, involving both genetic and environmental factors. CC The disease is inherited in 5-10% of the cases. ALS27 is an autosomal CC dominant form manifesting as toe walking and gait abnormalities in CC early childhood. {ECO:0000269|PubMed:34059824, CC ECO:0000269|PubMed:34459874, ECO:0000269|PubMed:36204986, CC ECO:0000269|PubMed:37308477}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Variants associated with CC ALS27 tend to disrupt the normal homeostatic regulation of serine CC palmitoyltransferase (SPT) by ORMDL proteins, resulting in up-regulated CC SPT activity and elevated levels of canonical SPT products. CC {ECO:0000269|PubMed:34059824}. CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A) CC [MIM:162400]: A form of hereditary sensory and autonomic neuropathy, a CC genetically and clinically heterogeneous group of disorders CC characterized by degeneration of dorsal root and autonomic ganglion CC cells, and by prominent sensory abnormalities with a variable degree of CC motor and autonomic dysfunction. The neurological phenotype is often CC complicated by severe infections, osteomyelitis, and amputations. CC HSAN1A is an autosomal dominant axonal form with onset in the second or CC third decades. Initial symptoms are loss of pain, touch, heat, and cold CC sensation over the feet, followed by distal muscle wasting and CC weakness. Loss of pain sensation leads to chronic skin ulcers and CC distal amputations. {ECO:0000269|PubMed:11242114, CC ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:19651702, CC ECO:0000269|PubMed:20504773, ECO:0000269|PubMed:21618344, CC ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:23454272, CC ECO:0000269|PubMed:24247255, ECO:0000269|PubMed:30420926}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Variants associated with HSAN1A tend to increase serine CC palmitoyltransferase (SPT) usage of alanine or glycine rather than CC serine, resulting in deoxysphingolipid synthesis. Deoxysphingolipids CC cannot be efficiently degraded by the cell machinery and cause cell CC toxicity. {ECO:0000305|PubMed:34059824}. CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent CC aminotransferase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y08685; CAA69941.1; -; mRNA. DR EMBL; AF286717; AAK29328.1; -; Genomic_DNA. DR EMBL; AF286703; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286704; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286705; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286706; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286707; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286708; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286709; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286710; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286711; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286712; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286713; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286714; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286715; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AF286716; AAK29328.1; JOINED; Genomic_DNA. DR EMBL; AK291546; BAF84235.1; -; mRNA. DR EMBL; AL391219; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL354751; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471089; EAW62804.1; -; Genomic_DNA. DR EMBL; BC007085; AAH07085.1; -; mRNA. DR CCDS; CCDS6692.1; -. [O15269-1] DR CCDS; CCDS6693.1; -. [O15269-2] DR RefSeq; NP_001268232.1; NM_001281303.1. DR RefSeq; NP_006406.1; NM_006415.3. [O15269-1] DR RefSeq; NP_847894.1; NM_178324.2. [O15269-2] DR PDB; 6M4N; EM; 3.80 A; A/E=1-473. DR PDB; 6M4O; EM; 3.40 A; B/S=1-473. DR PDB; 7CQI; EM; 3.20 A; C/S=1-473. DR PDB; 7CQK; EM; 3.30 A; C/S=1-473. DR PDB; 7K0I; EM; 3.30 A; A/D=1-473. DR PDB; 7K0J; EM; 3.10 A; A=1-473. DR PDB; 7K0K; EM; 2.60 A; A=1-473. DR PDB; 7K0L; EM; 3.40 A; A=1-473. DR PDB; 7K0M; EM; 2.90 A; A/E=1-473. DR PDB; 7K0N; EM; 3.10 A; A/E=1-473. DR PDB; 7K0O; EM; 3.10 A; A/E=1-473. DR PDB; 7K0P; EM; 3.10 A; A/E=1-473. DR PDB; 7K0Q; EM; 3.30 A; A=1-473. DR PDB; 7YIU; EM; 2.90 A; A/E=1-473. DR PDB; 7YIY; EM; 2.70 A; A/E=1-473. DR PDB; 7YJ1; EM; 3.10 A; A/E=1-473. DR PDB; 7YJ2; EM; 2.90 A; A/E=1-473. DR PDBsum; 6M4N; -. DR PDBsum; 6M4O; -. DR PDBsum; 7CQI; -. DR PDBsum; 7CQK; -. DR PDBsum; 7K0I; -. DR PDBsum; 7K0J; -. DR PDBsum; 7K0K; -. DR PDBsum; 7K0L; -. DR PDBsum; 7K0M; -. DR PDBsum; 7K0N; -. DR PDBsum; 7K0O; -. DR PDBsum; 7K0P; -. DR PDBsum; 7K0Q; -. DR PDBsum; 7YIU; -. DR PDBsum; 7YIY; -. DR PDBsum; 7YJ1; -. DR PDBsum; 7YJ2; -. DR AlphaFoldDB; O15269; -. DR EMDB; EMD-22598; -. DR EMDB; EMD-22599; -. DR EMDB; EMD-22600; -. DR EMDB; EMD-22601; -. DR EMDB; EMD-22602; -. DR EMDB; EMD-22604; -. DR EMDB; EMD-22605; -. DR EMDB; EMD-22606; -. DR EMDB; EMD-22608; -. DR EMDB; EMD-30079; -. DR EMDB; EMD-30080; -. DR EMDB; EMD-30081; -. DR EMDB; EMD-30082; -. DR EMDB; EMD-30441; -. DR EMDB; EMD-30442; -. DR EMDB; EMD-33864; -. DR EMDB; EMD-33866; -. DR EMDB; EMD-33868; -. DR EMDB; EMD-33869; -. DR SMR; O15269; -. DR BioGRID; 115809; 169. DR ComplexPortal; CPX-6663; Serine palmitoyltransferase complex, SPTLC1-SPTLC2-SPTSSA variant. DR ComplexPortal; CPX-6664; Serine palmitoyltransferase complex, SPTLC1-SPTLC2-SPTSSB variant. DR ComplexPortal; CPX-6665; Serine palmitoyltransferase complex, SPTLC1-SPTLC3-SPTSSA variant. DR ComplexPortal; CPX-6681; Serine palmitoyltransferase complex, SPTLC1-SPTLC3-SPTSSB variant. DR CORUM; O15269; -. DR DIP; DIP-45626N; -. DR IntAct; O15269; 85. DR MINT; O15269; -. DR STRING; 9606.ENSP00000262554; -. DR BindingDB; O15269; -. DR ChEMBL; CHEMBL1250343; -. DR DrugBank; DB00114; Pyridoxal phosphate. DR DrugBank; DB00133; Serine. DR iPTMnet; O15269; -. DR MetOSite; O15269; -. DR PhosphoSitePlus; O15269; -. DR SwissPalm; O15269; -. DR BioMuta; SPTLC1; -. DR EPD; O15269; -. DR jPOST; O15269; -. DR MassIVE; O15269; -. DR MaxQB; O15269; -. DR PaxDb; 9606-ENSP00000262554; -. DR PeptideAtlas; O15269; -. DR ProteomicsDB; 48557; -. [O15269-1] DR ProteomicsDB; 48558; -. [O15269-2] DR Pumba; O15269; -. DR Antibodypedia; 2269; 431 antibodies from 37 providers. DR DNASU; 10558; -. DR Ensembl; ENST00000262554.7; ENSP00000262554.2; ENSG00000090054.16. [O15269-1] DR Ensembl; ENST00000337841.4; ENSP00000337635.4; ENSG00000090054.16. [O15269-2] DR Ensembl; ENST00000690139.1; ENSP00000510483.1; ENSG00000090054.16. [O15269-2] DR GeneID; 10558; -. DR KEGG; hsa:10558; -. DR MANE-Select; ENST00000262554.7; ENSP00000262554.2; NM_006415.4; NP_006406.1. DR UCSC; uc004arl.3; human. [O15269-1] DR AGR; HGNC:11277; -. DR CTD; 10558; -. DR DisGeNET; 10558; -. DR GeneCards; SPTLC1; -. DR GeneReviews; SPTLC1; -. DR HGNC; HGNC:11277; SPTLC1. DR HPA; ENSG00000090054; Low tissue specificity. DR MalaCards; SPTLC1; -. DR MIM; 162400; phenotype. DR MIM; 605712; gene. DR MIM; 620285; phenotype. DR neXtProt; NX_O15269; -. DR OpenTargets; ENSG00000090054; -. DR Orphanet; 36386; Hereditary sensory and autonomic neuropathy type 1. DR Orphanet; 300605; Juvenile amyotrophic lateral sclerosis. DR PharmGKB; PA36106; -. DR VEuPathDB; HostDB:ENSG00000090054; -. DR eggNOG; KOG1358; Eukaryota. DR GeneTree; ENSGT00550000074872; -. DR HOGENOM; CLU_015846_0_1_1; -. DR InParanoid; O15269; -. DR OMA; LTKYGCG; -. DR OrthoDB; 9643at2759; -. DR PhylomeDB; O15269; -. DR TreeFam; TF314877; -. DR BioCyc; MetaCyc:HS01673-MONOMER; -. DR BRENDA; 2.3.1.50; 2681. DR PathwayCommons; O15269; -. DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis. DR SABIO-RK; O15269; -. DR SignaLink; O15269; -. DR SIGNOR; O15269; -. DR UniPathway; UPA00222; -. DR BioGRID-ORCS; 10558; 265 hits in 1179 CRISPR screens. DR ChiTaRS; SPTLC1; human. DR GeneWiki; SPTLC1; -. DR GenomeRNAi; 10558; -. DR Pharos; O15269; Tchem. DR PRO; PR:O15269; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O15269; Protein. DR Bgee; ENSG00000090054; Expressed in esophagus squamous epithelium and 210 other cell types or tissues. DR ExpressionAtlas; O15269; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0017059; C:serine C-palmitoyltransferase complex; IDA:UniProtKB. DR GO; GO:0035339; C:SPOTS complex; IDA:UniProtKB. DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro. DR GO; GO:0004758; F:serine C-palmitoyltransferase activity; IDA:UniProtKB. DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:MGI. DR GO; GO:1904504; P:positive regulation of lipophagy; IDA:MGI. DR GO; GO:1904649; P:regulation of fat cell apoptotic process; ISS:UniProtKB. DR GO; GO:0046511; P:sphinganine biosynthetic process; IEA:Ensembl. DR GO; GO:0030148; P:sphingolipid biosynthetic process; IDA:MGI. DR GO; GO:0006665; P:sphingolipid metabolic process; TAS:ProtInc. DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IEA:Ensembl. DR GO; GO:0046512; P:sphingosine biosynthetic process; IDA:ComplexPortal. DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1. DR InterPro; IPR004839; Aminotransferase_I/II. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small. DR PANTHER; PTHR13693; CLASS II AMINOTRANSFERASE/8-AMINO-7-OXONONANOATE SYNTHASE; 1. DR PANTHER; PTHR13693:SF2; SERINE PALMITOYLTRANSFERASE 1; 1. DR Pfam; PF00155; Aminotran_1_2; 1. DR SUPFAM; SSF53383; PLP-dependent transferases; 1. DR Genevisible; O15269; HS. PE 1: Evidence at protein level; KW 3D-structure; Acyltransferase; Alternative splicing; KW Amyotrophic lateral sclerosis; Disease variant; Endoplasmic reticulum; KW Lipid metabolism; Membrane; Neurodegeneration; Neuropathy; Phosphoprotein; KW Pyridoxal phosphate; Reference proteome; Sphingolipid metabolism; KW Transferase; Transmembrane; Transmembrane helix. FT CHAIN 1..473 FT /note="Serine palmitoyltransferase 1" FT /id="PRO_0000163853" FT TOPO_DOM 1..15 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 16..36 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 37..473 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..66 FT /note="Interaction with SPTLC2" FT /evidence="ECO:0000269|PubMed:33558762" FT MOD_RES 164 FT /note="Phosphotyrosine; by ABL" FT /evidence="ECO:0000269|PubMed:23629659" FT VAR_SEQ 143 FT /note="D -> E (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043127" FT VAR_SEQ 144..473 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043128" FT VARIANT 20 FT /note="A -> S (in ALS27; this variant can be caused by 2 FT genetic variations, one of which has been shown to affect FT splicing, leading to exon 2 skipping; in patient's whole FT blood sample, only exon 2 deletion was observed, but not FT the missense variant per se; when exon 2 deletion variant FT is expressed in induced pluripotent stem cells (iPSC) FT differentiated into motor neuron-like cells, increased FT production of sphinganine and ceramides is observed; when FT exon 2 deletion variant is transfected into HEK293 cells, FT decreased response to inhibition mediated by ORMDL3 or FT ceramide is observed; dbSNP:rs879254294)" FT /evidence="ECO:0000269|PubMed:34059824, FT ECO:0000269|PubMed:34459874" FT /id="VAR_088446" FT VARIANT 23 FT /note="Y -> F (in ALS27; increased production of FT sphinganine and ceramides, when expressed in induced FT pluripotent stem cells (iPSC) differentiated into motor FT neuron-like cells; decreased response to inhibition FT mediated by ORMDL3 and ceramide; no effect on the FT interaction with ORMDL3; dbSNP:rs1554716504)" FT /evidence="ECO:0000269|PubMed:34059824, FT ECO:0000269|PubMed:37308477" FT /id="VAR_088447" FT VARIANT 38 FT /note="L -> R (in ALS27; uncertain significance)" FT /evidence="ECO:0000269|PubMed:36204986" FT /id="VAR_088448" FT VARIANT 39 FT /note="Missing (in ALS27; increased production of FT sphinganine and ceramides, when expressed in induced FT pluripotent stem cells (iPSC) differentiated into motor FT neuron-like cells; decreased response to inhibition FT mediated by ORMDL3 and ceramide; no effect on the FT interaction with ORMDL3; dbSNP:rs1197928094)" FT /evidence="ECO:0000269|PubMed:34059824, FT ECO:0000269|PubMed:34459874" FT /id="VAR_088449" FT VARIANT 40..41 FT /note="Missing (in ALS27; increased production of FT sphinganine and ceramides, when expressed in induced FT pluripotent stem cells (iPSC) differentiated into motor FT neuron-like cells; decreased response to inhibition FT mediated by ORMDL3 and ceramide; no effect on the FT interaction with ORMDL3)" FT /evidence="ECO:0000269|PubMed:34059824" FT /id="VAR_088450" FT VARIANT 133 FT /note="C -> W (in HSAN1A; inactive in the heterodimeric SPT FT complex; largely reduced canonical activity towards serine; FT contrary to wild-type, uses alanine as substrate leading to FT the formation of 1-deoxysphinganine (1-deoxySa); does not FT affect the interaction with SPTLC2; dbSNP:rs119482082)" FT /evidence="ECO:0000269|PubMed:11242114, FT ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:20504773, FT ECO:0000269|PubMed:21618344, ECO:0000269|PubMed:22302274" FT /id="VAR_011392" FT VARIANT 133 FT /note="C -> Y (in HSAN1A; reduced canonical activity FT towards serine; does not affect the interaction with FT SPTLC2; dbSNP:rs119482081)" FT /evidence="ECO:0000269|PubMed:11242114, FT ECO:0000269|PubMed:19132419" FT /id="VAR_011393" FT VARIANT 144 FT /note="V -> D (in HSAN1A; reduced canonical activity FT towards serine; does not affect the interaction with FT SPTLC2; dbSNP:rs119482083)" FT /evidence="ECO:0000269|PubMed:11242114, FT ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:30420926" FT /id="VAR_011394" FT VARIANT 151 FT /note="R -> L (in dbSNP:rs45461899)" FT /evidence="ECO:0000269|PubMed:17060578" FT /id="VAR_037889" FT VARIANT 239 FT /note="R -> W (in a breast cancer sample; somatic mutation; FT dbSNP:rs542876370)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036610" FT VARIANT 310 FT /note="A -> G (found in a patient with HSAN1A; uncertain FT significance; dbSNP:rs768841574)" FT /evidence="ECO:0000269|PubMed:22302274" FT /id="VAR_068476" FT VARIANT 331 FT /note="S -> F (in HSAN1A; severe form with early onset; FT reduced canonical activity towards serine and increased FT production of deoxysphingolipids; no effect on subcellular FT location at the endoplasmic reticulum; dbSNP:rs267607087)" FT /evidence="ECO:0000269|PubMed:19651702, FT ECO:0000269|PubMed:21618344, ECO:0000269|PubMed:24247255" FT /id="VAR_066245" FT VARIANT 331 FT /note="S -> Y (in ALS27 and HSAN1A; reduced canonical FT activity towards serine and increased production of FT deoxysphingolipids; dbSNP:rs267607087)" FT /evidence="ECO:0000269|PubMed:23454272, FT ECO:0000269|PubMed:34459874" FT /id="VAR_073294" FT VARIANT 352 FT /note="A -> V (in HSAN1A; reduced canonical activity FT towards serine and increased production of FT deoxysphingolipids; no effect on subcellular location at FT the endoplasmic reticulum; dbSNP:rs267607088)" FT /evidence="ECO:0000269|PubMed:19651702, FT ECO:0000269|PubMed:21618344" FT /id="VAR_066246" FT VARIANT 387 FT /note="G -> A (does not affect catalytic activity towards FT serine; does not affect the interaction with SPTLC2; FT dbSNP:rs119482084)" FT /evidence="ECO:0000269|PubMed:15037712, FT ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:19651702" FT /id="VAR_037890" FT MUTAGEN 138 FT /note="F->A: Decreased catalytic activity with L-serine and FT palmitoyl-CoA as substrates." FT /evidence="ECO:0000269|PubMed:33558762" FT MUTAGEN 164 FT /note="Y->F: Increased serine palmitoyltransferase activity FT and sphingolipid content." FT /evidence="ECO:0000269|PubMed:23629659" FT MUTAGEN 337 FT /note="F->A: Strongly decreased catalytic activity with FT L-serine and palmitoyl-CoA as substrates." FT /evidence="ECO:0000269|PubMed:33558762" FT MUTAGEN 338 FT /note="S->A: Decreased catalytic activity with L-serine and FT palmitoyl-CoA as substrates." FT /evidence="ECO:0000269|PubMed:33558762" FT HELIX 11..18 FT /evidence="ECO:0007829|PDB:7K0M" FT HELIX 22..39 FT /evidence="ECO:0007829|PDB:7K0M" FT HELIX 54..63 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:7K0M" FT STRAND 91..95 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 98..102 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 108..110 FT /evidence="ECO:0007829|PDB:7K0J" FT HELIX 115..128 FT /evidence="ECO:0007829|PDB:7K0K" FT TURN 136..139 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 143..155 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 159..166 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 167..178 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 184..188 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 193..201 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 214..230 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 232..237 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 240..247 FT /evidence="ECO:0007829|PDB:7K0K" FT TURN 249..251 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 257..267 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 270..274 FT /evidence="ECO:0007829|PDB:7K0K" FT TURN 276..281 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:7K0M" FT HELIX 289..293 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 297..299 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 301..306 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 309..311 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 316..320 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 322..331 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 333..336 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 343..358 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 362..377 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 381..387 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 392..400 FT /evidence="ECO:0007829|PDB:7K0K" FT HELIX 405..420 FT /evidence="ECO:0007829|PDB:7K0K" FT TURN 421..423 FT /evidence="ECO:0007829|PDB:7K0K" FT TURN 433..435 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 436..438 FT /evidence="ECO:0007829|PDB:6M4O" FT STRAND 443..447 FT /evidence="ECO:0007829|PDB:7K0K" FT STRAND 450..452 FT /evidence="ECO:0007829|PDB:7K0N" FT HELIX 454..471 FT /evidence="ECO:0007829|PDB:7K0K" SQ SEQUENCE 473 AA; 52744 MW; BA9E056A869D2EA2 CRC64; MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL IEEWQPEPLV PPVPKDHPAL NYNIVSGPPS HKTVVNGKEC INFASFNFLG LLDNPRVKAA ALASLKKYGV GTCGPRGFYG TFDVHLDLED RLAKFMKTEE AIIYSYGFAT IASAIPAYSK RGDIVFVDRA ACFAIQKGLQ ASRSDIKLFK HNDMADLERL LKEQEIEDQK NPRKARVTRR FIVVEGLYMN TGTICPLPEL VKLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGINIDDI DLISANMENA LASIGGFCCG RSFVIDHQRL SGQGYCFSAS LPPLLAAAAI EALNIMEENP GIFAVLKEKC GQIHKALQGI SGLKVVGESL SPAFHLQLEE STGSREQDVR LLQEIVDQCM NRSIALTQAR YLEKEEKCLP PPSIRVVVTV EQTEEELERA ASTIKEVAQA VLL //