SPTC1_MOUSE
ID SPTC1_MOUSE Reviewed; 473 AA.
AC O35704; O54813; Q8BH11;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Serine palmitoyltransferase 1;
DE EC=2.3.1.50 {ECO:0000250|UniProtKB:O15269};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Kidney, and Liver;
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 [MRNA].
RC TISSUE=Kidney, and Testis;
RX PubMed=9405408; DOI=10.1074/jbc.272.51.32108;
RA Hanada K., Hara T., Nishijima M., Kuge O., Dickson R.C., Nagiec M.M.;
RT "A mammalian homolog of the yeast LCB1 encodes a component of serine
RT palmitoyltransferase, the enzyme catalyzing the first step in sphingolipid
RT synthesis.";
RL J. Biol. Chem. 272:32108-32114(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, Hypothalamus, and Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [5]
RP SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=1317856; DOI=10.1016/s0021-9258(19)49887-6;
RA Mandon E.C., Ehses I., Rother J., van Echten G., Sandhoff K.;
RT "Subcellular localization and membrane topology of serine
RT palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-
RT acyltransferase in mouse liver.";
RL J. Biol. Chem. 267:11144-11148(1992).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INDUCTION BY HIGH FAT DIET, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RTN4.
RX PubMed=26301690; DOI=10.1038/nm.3934;
RA Cantalupo A., Zhang Y., Kothiya M., Galvani S., Obinata H., Bucci M.,
RA Giordano F.J., Jiang X.C., Hla T., Di Lorenzo A.;
RT "Nogo-B regulates endothelial sphingolipid homeostasis to control vascular
RT function and blood pressure.";
RL Nat. Med. 21:1028-1037(2015).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=27818258; DOI=10.1016/j.cmet.2016.10.002;
RA Chaurasia B., Kaddai V.A., Lancaster G.I., Henstridge D.C., Sriram S.,
RA Galam D.L., Gopalan V., Prakash K.N., Velan S.S., Bulchand S., Tsong T.J.,
RA Wang M., Siddique M.M., Yuguang G., Sigmundsson K., Mellet N.A., Weir J.M.,
RA Meikle P.J., Bin M Yassin M.S., Shabbir A., Shayman J.A., Hirabayashi Y.,
RA Shiow S.T., Sugii S., Summers S.A.;
RT "Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation,
RT and Metabolism.";
RL Cell Metab. 24:820-834(2016).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=28100772; DOI=10.1074/jbc.m116.756460;
RA Alexaki A., Clarke B.A., Gavrilova O., Ma Y., Zhu H., Ma X., Xu L.,
RA Tuymetova G., Larman B.C., Allende M.L., Dunn T.M., Proia R.L.;
RT "De Novo Sphingolipid Biosynthesis Is Required for Adipocyte Survival and
RT Metabolic Homeostasis.";
RL J. Biol. Chem. 292:3929-3939(2017).
CC -!- FUNCTION: Serine palmitoyltransferase (SPT) (PubMed:28100772). The
CC heterodimer formed with SPTLC2 or SPTLC3 constitutes the catalytic
CC core. The composition of the serine palmitoyltransferase (SPT) complex
CC determines the substrate preference. 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. The
CC SPTLC1-SPTLC2-SPTSSB complex displays a strong preference for C18-CoA
CC substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme has the ability to
CC use a broader range of acyl-CoAs (By similarity). Required for
CC adipocyte cell viability and metabolic homeostasis (PubMed:28100772).
CC {ECO:0000250|UniProtKB:O15269, ECO:0000269|PubMed:28100772}.
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:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14762;
CC Evidence={ECO:0000250|UniProtKB:O15269};
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:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33684;
CC Evidence={ECO:0000250|UniProtKB:O15269};
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:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35676;
CC Evidence={ECO:0000250|UniProtKB:O15269};
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:0000250|UniProtKB:O15269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35680;
CC Evidence={ECO:0000250|UniProtKB:O15269};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:28100772}.
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. Interacts with ORMDL3 (By
CC similarity). Interacts with RTN4 (isoform B) (PubMed:26301690).
CC {ECO:0000250|UniProtKB:O15269, ECO:0000269|PubMed:26301690}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:1317856, ECO:0000269|PubMed:26301690}; Single-pass
CC membrane protein {ECO:0000269|PubMed:1317856}.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues. Highest
CC expression in brain, kidney and liver (PubMed:21994399). Expressed in
CC brown and white adipose tissues (PubMed:27818258).
CC {ECO:0000269|PubMed:21994399, ECO:0000269|PubMed:27818258}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed after birth, expression decreases
CC 2 weeks after birth and is maintained until, at least, 18 months.
CC {ECO:0000269|PubMed:21994399}.
CC -!- INDUCTION: Expression levels at protein level increase upon high-fat
CC diet. mRNA levels remain unchanged. {ECO:0000269|PubMed:21994399}.
CC -!- PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell
CC survival. {ECO:0000250|UniProtKB:O15269}.
CC -!- DISRUPTION PHENOTYPE: Knockout are lethal at embryonic stage
CC (PubMed:28100772). Conditional knockouts specific to the adipose tissue
CC develop adipose tissue but exhibit a striking age dependent loss of
CC adipose tissue accompanied by evidence of adipocyte death, increased
CC macrophage infiltration and tissue fibrosis. They also have elevated
CC fasting blood glucose, fatty liver and insulin resistance. They show a
CC significant reduction of total sphingomyelin levels in the adipose
CC tissue (PubMed:28100772). {ECO:0000269|PubMed:28100772}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; X95641; CAA64897.1; -; mRNA.
DR EMBL; AF003823; AAC02264.1; -; mRNA.
DR EMBL; AK053207; BAC35310.1; -; mRNA.
DR EMBL; AK079578; BAC37690.1; -; mRNA.
DR EMBL; AK084391; BAC39172.1; -; mRNA.
DR EMBL; AK084445; BAC39185.1; -; mRNA.
DR EMBL; BC046323; AAH46323.1; -; mRNA.
DR CCDS; CCDS26521.1; -.
DR RefSeq; NP_033295.2; NM_009269.2.
DR AlphaFoldDB; O35704; -.
DR SMR; O35704; -.
DR BioGRID; 234529; 6.
DR STRING; 10090.ENSMUSP00000021920; -.
DR GuidetoPHARMACOLOGY; 2509; -.
DR iPTMnet; O35704; -.
DR PhosphoSitePlus; O35704; -.
DR EPD; O35704; -.
DR MaxQB; O35704; -.
DR PaxDb; O35704; -.
DR PeptideAtlas; O35704; -.
DR PRIDE; O35704; -.
DR ProteomicsDB; 257058; -.
DR Antibodypedia; 2269; 402 antibodies from 37 providers.
DR DNASU; 268656; -.
DR Ensembl; ENSMUST00000021920; ENSMUSP00000021920; ENSMUSG00000021468.
DR GeneID; 268656; -.
DR KEGG; mmu:268656; -.
DR UCSC; uc007qnk.2; mouse.
DR CTD; 10558; -.
DR MGI; MGI:1099431; Sptlc1.
DR VEuPathDB; HostDB:ENSMUSG00000021468; -.
DR eggNOG; KOG1358; Eukaryota.
DR GeneTree; ENSGT00550000074872; -.
DR HOGENOM; CLU_015846_0_1_1; -.
DR InParanoid; O35704; -.
DR OMA; RNTPTFA; -.
DR OrthoDB; 438936at2759; -.
DR PhylomeDB; O35704; -.
DR TreeFam; TF314877; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR BioGRID-ORCS; 268656; 25 hits in 76 CRISPR screens.
DR PRO; PR:O35704; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; O35704; protein.
DR Bgee; ENSMUSG00000021468; Expressed in gastrula and 257 other tissues.
DR Genevisible; O35704; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017059; C:serine C-palmitoyltransferase complex; ISA:MGI.
DR GO; GO:0035339; C:SPOTS complex; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004758; F:serine C-palmitoyltransferase activity; IMP:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:MGI.
DR GO; GO:0061724; P:lipophagy; ISO:MGI.
DR GO; GO:1904504; P:positive regulation of lipophagy; ISO:MGI.
DR GO; GO:1904649; P:regulation of fat cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0046511; P:sphinganine biosynthetic process; IMP:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; ISO:MGI.
DR GO; GO:0006665; P:sphingolipid metabolic process; IMP:UniProtKB.
DR GO; GO:0006686; P:sphingomyelin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IMP:MGI.
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 Acyltransferase; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Phosphoprotein; Pyridoxal phosphate; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..473
FT /note="Serine palmitoyltransferase 1"
FT /id="PRO_0000163855"
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:0000250|UniProtKB:O15269"
FT CONFLICT 6..7
FT /note="EQ -> DE (in Ref. 2; AAC02264)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="V -> E (in Ref. 2; AAC02264)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="T -> A (in Ref. 1; CAA64897 and 2; AAC02264)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="S -> T (in Ref. 2; AAC02264)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="I -> V (in Ref. 1; CAA64897 and 2; AAC02264)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 52535 MW; 5B037E344DDEB4A7 CRC64;
MATVAEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLVF SKTYKLQERS DLTAKEKEEL
IEEWQPEPLV PPVSKNHPAL NYNIVSGPPT HNIVVNGKEC VNFASFNFLG LLANPRVKAT
AFSSLKKYGV GTCGPRGFYG TFDVHLDLEE RLAKFMKTEE AIIYSYGFST IASAIPAYSK
RGDIIFVDSA ACFAIQKGLQ ASRSDIKLFK HNDVADLERL LKEQEIEDQK NPRKARVTRR
FIVVEGLYMN TGTICPLPEL VKLKYKYKAR IFLEESLSFG VLGEHGRGVT EHYGISIDDI
DLISANMENA LASVGGFCCG RSFVVDHQRL SGQGYCFSAS LPPLLAAAAI EALNIMEENP
DIFAVLKKKC QNIHKSLQGV SGLKVVGESL SPALHLQLEE STGSREKDVK LLQAIVDQCM
DKGIALTQAR YLDKEEKCLP PPSIRVVVTV EQTEEELQRA ASTIREAAQA VLL
