SPTC1_HUMAN
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 03-AUG-2022, entry version 201.
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, 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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP VARIANTS HSAN1A PHE-331 AND VAL-352.
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 [19]
RP CHARACTERIZATION OF VARIANTS HSAN1A TYR-133; TRP-133 AND ASP-144,
RP CHARACTERIZATION OF VARIANT ALA-387, AND LACK OF ASSOCIATION OF VARIANT
RP ALA-387 WITH HSAN1A.
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 [20]
RP VARIANT HSAN1A PHE-331, AND CHARACTERIZATION OF VARIANTS HSAN1A PHE-331 AND
RP VAL-352.
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 [21]
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 [22]
RP INVOLVEMENT IN HMSN, VARIANT TYR-331, AND CHARACTERIZATION OF VARIANT
RP 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 [23]
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 [24]
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).
CC -!- FUNCTION: Serine palmitoyltransferase (SPT) (PubMed:19416851). The
CC heterodimer formed with SPTLC2 or SPTLC3 constitutes the catalytic core
CC (PubMed:19416851). The composition of the serine palmitoyltransferase
CC (SPT) complex determines the substrate preference (PubMed:19416851).
CC The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA
CC substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and
CC C16-CoA as substrates, with a slight preference for C14-CoA
CC (PubMed:19416851). The SPTLC1-SPTLC2-SPTSSB complex shows a strong
CC preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB
CC isozyme displays an ability to use a broader range of acyl-CoAs,
CC without apparent preference (PubMed:19416851). Required for adipocyte
CC cell viability and metabolic homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:O35704, ECO:0000269|PubMed:19416851}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.75 mM for serine {ECO:0000269|PubMed:20504773};
CC Vmax=1350 pmol/min/mg enzyme {ECO:0000269|PubMed:20504773};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:19416851}.
CC -!- SUBUNIT: Heterodimer with SPTLC2 or SPTLC3. Component of the serine
CC palmitoyltransferase (SPT) complex, composed of SPTLC1, either SPTLC2
CC or SPTLC3, and either SPTSSA or SPTSSB. The composition of the complex
CC will define the substrate specificity. Interacts with SPTSSA and
CC SPTSSB; the interaction is direct (PubMed:19416851). Interacts with
CC ORMDL3 (PubMed:20182505). Interacts with RTN4 (isoform B) (By
CC similarity). {ECO:0000250|UniProtKB:O35704,
CC ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:20182505}.
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:0000250|UniProtKB:O35704}; 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 -!- PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell
CC survival. {ECO:0000269|PubMed:23629659}.
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:24247255,
CC ECO:0000269|PubMed:30420926}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=SPTLC1 mutations at Ser-331 are responsible for severe
CC hereditary motor and sensory neuropathy (HMSN) forms, whose core
CC features are severe, diffuse muscle wasting and hypotonia, motor and
CC sensory disturbances, foot ulcers, amputations and/or burns, joint
CC hypermobility, cataracts and considerable growth retardation.
CC {ECO:0000269|PubMed:23454272}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
CC -!- CAUTION: Variant Ala-387 has been originally thought to cause HSAN1A
CC (PubMed:15037712). Subsequently, it has been shown to be a rare, benign
CC polymorphism found in homozygous state in a healthy individual
CC (PubMed:19132419). {ECO:0000305|PubMed:15037712,
CC ECO:0000305|PubMed:19132419}.
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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 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 AlphaFoldDB; O15269; -.
DR SMR; O15269; -.
DR BioGRID; 115809; 121.
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; 82.
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; O15269; -.
DR PeptideAtlas; O15269; -.
DR PRIDE; O15269; -.
DR ProteomicsDB; 48557; -. [O15269-1]
DR ProteomicsDB; 48558; -. [O15269-2]
DR Antibodypedia; 2269; 402 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 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 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; RNTPTFA; -.
DR OrthoDB; 438936at2759; -.
DR PhylomeDB; O15269; -.
DR TreeFam; TF314877; -.
DR BioCyc; MetaCyc:HS01673-MON; -.
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; 256 hits in 1099 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 208 other tissues.
DR ExpressionAtlas; O15269; baseline and differential.
DR Genevisible; O15269; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 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 Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Alternative splicing; Disease variant;
KW Endoplasmic reticulum; Lipid metabolism; Membrane; Neurodegeneration;
KW Neuropathy; Phosphoprotein; Pyridoxal phosphate; Reference proteome;
KW Sphingolipid metabolism; 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 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 133
FT /note="C -> W (in HSAN1A; inactive in the heterodimeric SPT
FT complex; largely reduced activity with serine as substrate,
FT but nearly no effect on serine affinity in the
FT heterotrimeric SPT complex; in contrast to wild-type is
FT able to use alanine as substrate leading to the formation
FT of 1-deoxysphinganine (1-deoxySa); does not interfere with
FT SPT complex formation; dbSNP:rs119482082)"
FT /evidence="ECO:0000269|PubMed:11242114,
FT ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:20504773,
FT ECO:0000269|PubMed:22302274"
FT /id="VAR_011392"
FT VARIANT 133
FT /note="C -> Y (in HSAN1A; reduced activity; does not
FT interfere with SPT complex formation; 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; present with both painful and
FT painles phenotypes; reduced activity; does not interfere
FT with SPT complex formation; 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 pathological 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 activity; 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 (probable disease-associated variant found in
FT severe HMSN; reduced activity; dbSNP:rs267607087)"
FT /evidence="ECO:0000269|PubMed:23454272"
FT /id="VAR_073294"
FT VARIANT 352
FT /note="A -> V (in HSAN1A; reduced activity;
FT 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 activity; does not interfere
FT with SPT complex formation; dbSNP:rs119482084)"
FT /evidence="ECO:0000269|PubMed:15037712,
FT ECO:0000269|PubMed:19132419"
FT /id="VAR_037890"
FT MUTAGEN 164
FT /note="Y->F: Increased serine palmitoyltransferase activity
FT and sphingolipid content."
FT /evidence="ECO:0000269|PubMed:23629659"
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
