ID   SPTC1_PONAB             Reviewed;         473 AA.
AC   Q5R9T5; Q5R793;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 99.
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;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Heart, and Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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
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, with
CC       a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows
CC       a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-
CC       SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs,
CC       without apparent preference (By similarity). Required for adipocyte
CC       cell viability and metabolic homeostasis (By similarity).
CC       {ECO:0000250|UniProtKB:O15269, ECO:0000250|UniProtKB:O35704}.
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   -!- ACTIVITY REGULATION: SPT complex catalytic activity is negatively
CC       regulated by ORMDL proteins, including ORMDL3, in the presence of
CC       ceramides (By similarity). 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 (By similarity).
CC       {ECO:0000250|UniProtKB:O15269, ECO:0000250|UniProtKB:Q3MHG1}.
CC   -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC   -!- SUBUNIT: Component of the serine palmitoyltransferase (SPT) complex,
CC       which is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The
CC       heterodimer with SPTLC2 or SPTLC3 forms the catalytic core of the
CC       enzyme, while SPTSSA or SPTSSB subunits determine substrate
CC       specificity. SPT also interacts with ORMDL proteins, especially ORMDL3,
CC       which negatively regulate SPT activity in the presence of ceramides.
CC       Forms dimers of heterodimers with SPTLC2 (By similarity). Interacts
CC       with RTN4 (By similarity). {ECO:0000250|UniProtKB:O15269,
CC       ECO:0000250|UniProtKB:O35704}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:O35704}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:O35704}.
CC   -!- DOMAIN: The transmembrane domain is involved in the interaction with
CC       ORMDL3. {ECO:0000250|UniProtKB:O15269}.
CC   -!- PTM: Phosphorylation at Tyr-164 inhibits activity and promotes cell
CC       survival. {ECO:0000250|UniProtKB:O15269}.
CC   -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC       aminotransferase family. {ECO:0000305}.
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DR   EMBL; CR859297; CAH91475.1; -; mRNA.
DR   EMBL; CR860225; CAH92367.1; -; mRNA.
DR   RefSeq; NP_001126393.1; NM_001132921.1.
DR   AlphaFoldDB; Q5R9T5; -.
DR   SMR; Q5R9T5; -.
DR   STRING; 9601.ENSPPYP00000021706; -.
DR   Ensembl; ENSPPYT00000022593.2; ENSPPYP00000021706.2; ENSPPYG00000019371.3.
DR   GeneID; 100173375; -.
DR   KEGG; pon:100173375; -.
DR   CTD; 10558; -.
DR   eggNOG; KOG1358; Eukaryota.
DR   GeneTree; ENSGT00550000074872; -.
DR   InParanoid; Q5R9T5; -.
DR   OMA; LTKYGCG; -.
DR   OrthoDB; 9643at2759; -.
DR   UniPathway; UPA00222; -.
DR   Proteomes; UP000001595; Chromosome 9.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR   GO; GO:0046513; P:ceramide biosynthetic process; IEA:Ensembl.
DR   GO; GO:1904504; P:positive regulation of lipophagy; IEA:Ensembl.
DR   GO; GO:1904649; P:regulation of fat cell apoptotic process; ISS:UniProtKB.
DR   GO; GO:0006665; P:sphingolipid metabolic process; ISS:UniProtKB.
DR   GO; GO:0046512; P:sphingosine biosynthetic process; IEA:Ensembl.
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.
PE   2: Evidence at transcript 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_0000327869"
FT   TRANSMEM        16..36
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..66
FT                   /note="Interaction with SPTLC2"
FT                   /evidence="ECO:0000250|UniProtKB:O15269"
FT   MOD_RES         164
FT                   /note="Phosphotyrosine; by ABL"
FT                   /evidence="ECO:0000250|UniProtKB:O15269"
FT   CONFLICT        158
FT                   /note="T -> I (in Ref. 1; CAH92367)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   473 AA;  52867 MW;  64BCBB758A79B632 CRC64;
     MATATEQWVL VEMVQALYEA PAYHLILEGI LILWIIRLLF SKTYKLQERS DLTVKEKEEL
     IEEWQPEPLV PLVPKDHPAL NYNIVSGPPS HKIVVNGKEC 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 RQIHKALQGI SGLKVVGEPL SPAFHLQLEE STGSREQDVR LLQEIVDQCM
     NRSIALTQAR YLEKEEKCLP PPSIRVVVTV EQTEEELDRA ASTIKEVAQA VLL
//