SPTLC1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred ER localization for the SPT catalytic subunit. SPTLC1 is a single-pass ER membrane protein, so ER localization is correct, though the more specific term (ER membrane) is also annotated separately. Reason: SPTLC1 is an integral ER membrane protein and the SPT complex acts at the ER; the IBA is consistent with experimental and IEA annotations. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0046512 sphingosine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that SPTLC1 is involved in sphingosine (long-chain base) biosynthesis, the initial de novo sphingolipid step catalyzed by SPT. Reason: SPT produces the long-chain base precursor of sphingosine; this represents the committed step of the pathway and is well supported. Supporting Evidence: PMID:9363775 is the key enzyme in sphingolipid
GO:0046513 ceramide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that SPTLC1 participates in ceramide biosynthesis. The SPT-catalyzed step is the entry point of the de novo pathway that produces long-chain bases, which are N-acylated to ceramide. Reason: SPT initiates the de novo pathway whose downstream product is ceramide; the involved_in relationship for the pathway entry enzyme is appropriate. Supporting Evidence: PMID:9363775 is the key enzyme in sphingolipid
GO:0004758 serine C-palmitoyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core serine C-palmitoyltransferase molecular function (EC 2.3.1.50 / RHEA:14761) to SPTLC1. This is the defining catalytic activity of the SPT complex and matches experimental annotations. Reason: The IEA correctly captures the core molecular function; it is supported by the mapped RHEA/EC and by direct experimental annotations from the same term. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt catalyzes the initial and rate-limiting step in
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of ER membrane localization, consistent with the single-pass ER membrane topology of SPTLC1. Reason: Matches the experimentally supported subcellular location; ER membrane is the core CC for this subunit. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro-based assignment of PLP binding from the class-II PLP-dependent aminotransferase signature. SPT is a PLP-dependent enzyme, but the PLP-binding catalytic lysine resides on SPTLC2, not SPTLC1; SPTLC1 retains the fold but lacks the catalytic lysine. Reason: The PLP cofactor is bound at the SPTLC2 active-site lysine within the heterodimer; the InterPro signature is over-propagated from the family fold to the non-catalytic SPTLC1 subunit. Retained but flagged as over-annotation, since PLP is not directly coordinated by SPTLC1. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt Belongs to the class-II pyridoxal-phosphate-dependent
GO:0005515 protein binding	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	MARK AS OVER ANNOTATED	Summary: IntAct-curated physical interactions of SPTLC1 with SPT complex partners (SPTLC2, SPTLC3, SPTSSA). The informative content (SPT complex membership and small-subunit interactions) is captured by GO:0017059. Reason: Bare 'protein binding' is uninformative; the specific and biologically meaningful assemblies are already represented by the serine palmitoyltransferase complex annotations. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and
GO:0005515 protein binding	IPI PMID:20182505 Orm family proteins mediate sphingolipid homeostasis.	MARK AS OVER ANNOTATED	Summary: IntAct-curated interaction of SPTLC1 with ORMDL3 (the negative regulator of SPT). Informative regulatory context is better captured by complex membership and activity-regulation terms. Reason: Bare 'protein binding' adds no functional detail beyond the ORMDL-SPT interaction already documented; retained but flagged as over-annotation. Supporting Evidence: PMID:20182505 complex with serine palmitoyltransferase, the first and rate-limiting enzyme in
GO:0005515 protein binding	IPI PMID:33558761 Structural insights into the regulation of human serine palm...	MARK AS OVER ANNOTATED	Summary: Cryo-EM/interaction evidence for SPTLC1 within the human SPT holocomplex (with SPTLC2, ssSPTa/SPTSSA, ORMDL3). The specific assembly is represented by GO:0017059. Reason: Bare 'protein binding' is uninformative relative to the structurally defined SPT holocomplex membership already annotated. Supporting Evidence: PMID:33558761 palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1
GO:0005515 protein binding	IPI PMID:33558762 Structural insights into the assembly and substrate selectiv...	MARK AS OVER ANNOTATED	Summary: Structural/interaction evidence for SPTLC1 within the SPT-ORMDL3 complex (SPTLC1-SPTLC2-SPTssa dimer of heterodimers). Captured by complex membership. Reason: Bare 'protein binding' adds nothing beyond the structurally defined SPT complex annotation; retained but flagged. Supporting Evidence: PMID:33558762 SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: OpenCell endogenous-tagging interactome detecting SPTLC1-SPTLC2 physical association at scale. Uninformative bare term. Reason: Bare protein binding is uninformative; the SPTLC1-SPTLC2 interaction is already represented by serine palmitoyltransferase complex membership. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt O15269; O15270: SPTLC2
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the broad sphingolipid metabolic process. SPT catalyzes the entry reaction of sphingolipid metabolism. Reason: Correct but general; the more specific biosynthetic terms (GO:0030148, GO:0046512, GO:0046513) are also annotated and are the core BP terms. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt PATHWAY: Lipid metabolism; sphingolipid metabolism.
GO:0006686 sphingomyelin biosynthetic process	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Electronic (ARBA/ortholog) assignment of sphingomyelin biosynthesis. Sphingomyelin synthesis (headgroup transfer onto ceramide by sphingomyelin synthases in the Golgi) is several steps downstream of the SPT-catalyzed entry reaction and is not a direct SPTLC1 function. Reason: This is a downstream pathway terminus, not the reaction SPTLC1 participates in; over-broad electronic mapping. The core biosynthetic role is captured by the LCB/ceramide biosynthesis terms. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt catalyzes the initial and rate-limiting step in
GO:1904649 regulation of fat cell apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl orthology transfer from mouse Sptlc1 (O35704) of a role in regulating adipocyte apoptosis, reflecting the requirement of de novo sphingolipid synthesis for adipocyte viability. Reason: Peripheral, physiology-level phenotype transferred by orthology; not the core molecular/biosynthetic function of the enzyme, but plausible given sphingolipid requirements for adipocyte homeostasis. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt Required for adipocyte cell
GO:0005789 endoplasmic reticulum membrane	NAS PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: ComplexPortal non-traceable assertion of ER membrane localization for the SPT complex, consistent with all other localization evidence. Reason: ER membrane is the well-established core location; corroborated by EXP, IEA and TAS annotations. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0017059 serine palmitoyltransferase complex	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: SPTLC1 is a subunit of the serine palmitoyltransferase complex, shown by identification of SPTLC1 in the SPT complex and its interaction with the small subunits SPTSSA/SPTSSB. Reason: Core cellular-component annotation; SPTLC1 is a defining, obligate subunit of the SPT enzyme complex. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and
GO:0017059 serine palmitoyltransferase complex	IPI PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: Cryo-EM of the human SPT holocomplex confirms SPTLC1 as a catalytic-core subunit of the serine palmitoyltransferase complex. Reason: Structurally validated core CC annotation for the SPT complex. Supporting Evidence: PMID:33558761 palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1
GO:0046512 sphingosine biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct assay of SPT isozymes containing SPTLC1 shows production of long-chain (sphingoid) bases with distinct acyl-CoA preferences, supporting a role in sphingosine/long-chain-base biosynthesis. Reason: Experimentally supported involvement in the LCB-producing entry step of the de novo pathway. Supporting Evidence: PMID:19416851 differences in acyl-CoA preference that offer a potential explanation for the
GO:0046512 sphingosine biosynthetic process	IDA PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: Structural and biochemical characterization of the SPT holocomplex containing SPTLC1 supports its role in long-chain base (sphingosine precursor) biosynthesis. Reason: Consistent with the enzyme's defined catalytic role at the pathway entry. Supporting Evidence: PMID:33558761 palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence localizing SPTLC1 to the endoplasmic reticulum. Reason: Direct localization evidence consistent with the ER membrane topology; the more specific ER membrane term is also annotated. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	EXP PMID:21618344 Characterization of two mutations in the SPTLC1 subunit of s...	ACCEPT	Summary: Experimental characterization of HSAN1-associated SPTLC1 mutants included determination of subcellular location at the ER membrane. Reason: Core CC annotation; SPTLC1 is a single-pass ER membrane protein. The curator read the full text; the UniProt record cites this paper for the ER membrane subcellular location. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt Endoplasmic reticulum membrane
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: SPTLC1-containing SPT isozymes were directly assayed for serine C-palmitoyltransferase activity. The contributes_to qualifier reflects that catalysis requires the SPTLC1-SPTLC2/3 heterodimer. Reason: Direct experimental support for the core molecular function; contributes_to is appropriate because SPTLC1 provides part of the active-site environment within the obligate heterodimer. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in
GO:0006686 sphingomyelin biosynthetic process	IDA PMID:30242129 Complex formation of sphingomyelin synthase 1 with glucosylc...	MARK AS OVER ANNOTATED	Summary: This annotation attributes sphingomyelin biosynthesis to SPTLC1 via a paper (PMID:30242129) that studies the SMS1 (SGMS1)-GCS (UGCG) Golgi complex. The cached full text does not mention SPTLC1 or serine palmitoyltransferase at all, and sphingomyelin synthesis (phosphocholine transfer onto ceramide) is several steps downstream of the SPT-catalyzed entry reaction. Reason: The reference does not assay SPTLC1 and sphingomyelin biosynthesis is not a direct SPTLC1 function; it is a downstream terminus of the broader pathway. Per curation policy for experimental annotations this is flagged as over-annotation rather than removed. Supporting Evidence: PMID:30242129 initiated by the condensation of serine and palmitoyl-CoA
GO:0046513 ceramide biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct characterization of SPTLC1-containing SPT isozymes and their long-chain base output supports involvement in the de novo pathway that yields ceramide. Reason: SPT initiates the pathway whose downstream product is ceramide; experimentally supported involvement. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in
GO:0006688 glycosphingolipid biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	KEEP AS NON CORE	Summary: SPT activity produces long-chain bases that feed the wider sphingolipid network, including glycosphingolipids. The direct enzymatic product is a 3-ketosphingoid, and glycosphingolipid formation is many steps downstream. Reason: Correct as a pathway-level involvement but distal to the SPTLC1-catalyzed step; retained as non-core rather than a defining function. Supporting Evidence: PMID:19416851 differences in acyl-CoA preference that offer a potential explanation for the
GO:0017059 serine palmitoyltransferase complex	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Identification of SPTLC1 in the SPT complex, including its association with SPTLC2/3 and the small subunits. Reason: Core CC annotation; SPTLC1 is an obligate subunit of the SPT complex. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and
GO:0098554 cytoplasmic side of endoplasmic reticulum membrane	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: The catalytic domain of SPTLC1 (residues 37-473) is cytoplasmic, so the SPT active site faces the cytoplasmic side of the ER membrane, where long-chain base synthesis occurs. Reason: Consistent with the single-pass topology (lumenal N-terminus, TM 16-36, cytoplasmic catalytic domain); de novo LCB synthesis is known to occur on the cytosolic ER leaflet. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt TOPO_DOM 37..473
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-428127	ACCEPT	Summary: Reactome traceable assertion placing the SPTLC complexes at the ER membrane where they transfer acyl-CoA onto serine. Reason: Consistent with all other localization evidence; ER membrane is the core CC. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:1904649 regulation of fat cell apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse Sptlc1 of a role in regulating adipocyte apoptosis, mirroring the requirement of de novo sphingolipid synthesis for adipocyte viability. Reason: Peripheral orthology-based phenotype; not the core catalytic/biosynthetic function but biologically plausible. Supporting Evidence: file:human/SPTLC1/SPTLC1-uniprot.txt Required for adipocyte cell
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: SPTLC1-containing SPT complexes were assayed for de novo sphingolipid biosynthetic (serine C-palmitoyltransferase) activity in the context of ORMDL/SPT stoichiometry experiments. Reason: Direct support for the core molecular function; contributes_to reflects the obligate heterodimeric catalytic core. Supporting Evidence: PMID:25691431 enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT).
GO:0017059 serine palmitoyltransferase complex	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: SPTLC1 shown to form stable complexes with ORMDL and the SPT machinery, confirming its membership in the serine palmitoyltransferase complex. Reason: Core CC annotation supported by direct assay of SPT/ORMDL complexes. Supporting Evidence: PMID:25691431 ORMDLs and SPT form stable
GO:0046513 ceramide biosynthetic process	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: SPTLC1/SPT activity controls flux into the de novo pathway that produces ceramide; manipulating ORMDL/SPT levels alters cellular ceramide/sphingolipid levels. Reason: Appropriate acts_upstream_of_or_within relationship for the pathway-entry enzyme whose activity determines ceramide output. Supporting Evidence: PMID:25691431 enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT).
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	ACCEPT	Summary: Overexpression of serine palmitoyltransferase (elevating de novo sphingolipid biosynthesis) was used to assay SPT-dependent flux, supporting the core serine C-palmitoyltransferase activity contributed by SPTLC1. Reason: Direct support for the core molecular function within the obligate SPT heterodimer (contributes_to). Supporting Evidence: PMID:25332431 overexpression of serine palmitoyltransferase to elevate de novo sphingolipid
GO:0030148 sphingolipid biosynthetic process	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	ACCEPT	Summary: Elevating SPT activity increases de novo sphingolipid biosynthesis in the liver, placing SPTLC1 upstream of/within the sphingolipid biosynthetic process. Reason: Core biosynthetic-process annotation; the SPT-catalyzed step is the committed entry into de novo sphingolipid synthesis. Supporting Evidence: PMID:25332431 overexpression of serine palmitoyltransferase to elevate de novo sphingolipid
GO:1904504 positive regulation of lipophagy	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	KEEP AS NON CORE	Summary: In mouse liver, elevating de novo sphingolipid synthesis by SPT overexpression induces autophagy, linking SPT activity to lipophagy/autophagy induction. This is an indirect, physiology-level consequence of elevated flux. Reason: A downstream, indirect regulatory effect of excess sphingolipid synthesis rather than a direct molecular function of SPTLC1; retained as non-core. Supporting Evidence: PMID:25332431 overexpression of serine palmitoyltransferase to elevate de novo sphingolipid
GO:0017059 serine palmitoyltransferase complex	IDA PMID:20182505 Orm family proteins mediate sphingolipid homeostasis.	ACCEPT	Summary: SPTLC1 was shown to form a conserved complex with the Orm/ORMDL proteins and serine palmitoyltransferase, confirming SPT complex membership. Reason: Core CC annotation; SPTLC1 is an obligate subunit of the SPT complex. Supporting Evidence: PMID:20182505 complex with serine palmitoyltransferase, the first and rate-limiting enzyme in
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct assay of SPTLC1-containing SPT isozymes demonstrates serine C-palmitoyltransferase (EC 2.3.1.50) activity; this UniProt annotation uses the enables qualifier for the enzymatic activity of the complex containing SPTLC1. Reason: This is the defining, experimentally demonstrated core molecular function of the SPT enzyme that SPTLC1 is part of. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in
GO:0030148 sphingolipid biosynthetic process	TAS PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Traceable assertion that SPTLC1/SPT is involved in sphingolipid biosynthesis, the pathway whose committed first step it catalyzes. Reason: Core biological-process annotation, directly reflecting the enzyme's role. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in
GO:0004758 serine C-palmitoyltransferase activity	TAS PMID:9363775 Human and murine serine-palmitoyl-CoA transferase--cloning, ...	ACCEPT	Summary: The founding cloning/characterization paper establishes SPT (EC 2.3.1.50) as the key enzyme in sphingolipid biosynthesis, catalyzing the PLP-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Reason: Core molecular-function annotation with an authoritative traceable source. Supporting Evidence: PMID:9363775 It catalyzes the pyridoxal-5'-phosphate-dependent condensation of
GO:0006665 sphingolipid metabolic process	TAS PMID:9363775 Human and murine serine-palmitoyl-CoA transferase--cloning, ...	ACCEPT	Summary: Traceable assertion that SPT is the key enzyme in sphingolipid metabolism. Reason: Correct but broad; the specific biosynthetic-process terms are the core BP annotations. Retained as supporting general context. Supporting Evidence: PMID:9363775 is the key enzyme in sphingolipid

Gene Description

Existing Annotations Review

Core Functions

Serine C-palmitoyltransferase activity as the catalytic core subunit of the serine palmitoyltransferase (SPT) complex, catalyzing the PLP-dependent condensation of L-serine and palmitoyl-CoA to 3-ketodihydrosphingosine, the first and committed step of de novo sphingolipid biosynthesis.

References

📚 Additional Documentation

Notes

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