SPTLC2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0017059 serine palmitoyltransferase complex	IBA GO_REF:0000033	ACCEPT	Summary: SPTLC2 is a subunit of the serine palmitoyltransferase (SPT) complex, forming the catalytic core together with SPTLC1. Phylogenetically inferred and strongly supported by experimental and structural evidence. Reason: Correct and core. The catalytic heterodimer of SPTLC1 and SPTLC2 is the enzymatic core of the ER-localized SPT complex, established biochemically and by multiple cryo-EM structures. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and PMID:33558762 form a dimer of heterodimers as the catalytic core
GO:0046512 sphingosine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: SPT catalyzes the first, committed step of de novo sphingoid base (long-chain base) biosynthesis, the pathway leading to sphingosine and other sphingoid bases. Reason: Correct biological process. SPTLC2 initiates the pathway that produces the sphingoid base backbone; sphingosine biosynthesis is a direct downstream consequence of SPT activity. Supporting Evidence: PMID:19416851 catalyzes the first committed step in
GO:0004758 serine C-palmitoyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Serine C-palmitoyltransferase activity is the defining molecular function of SPTLC2: PLP-dependent condensation of L-serine with palmitoyl-CoA to form 3-ketodihydrosphingosine. This is the exact current GOA MF term for this gene. Reason: Core molecular function, phylogenetically inferred and supported by direct enzymatic assays. This is the catalytic activity of the SPTLC1/SPTLC2 core. (Strictly, catalysis requires the SPTLC1/SPTLC2 heterodimer, so contributes_to is the more precise qualifier; the function itself is unambiguously correct.) Supporting Evidence: PMID:9363775 It catalyzes the pyridoxal-5'-phosphate-dependent condensation of
GO:0046513 ceramide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: SPT initiates de novo sphingolipid synthesis, the pathway that generates the sphingoid base and, via subsequent enzymes, ceramide. Reason: Correct. Ceramide biosynthesis begins with the SPT-catalyzed step; SPTLC2 is required for de novo ceramide production. Phylogenetically inferred and experimentally supported. Supporting Evidence: PMID:19416851 catalyzes the first committed step in
GO:0004758 serine C-palmitoyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of the core catalytic activity via combined automated methods (ARBA/RHEA/EC 2.3.1.50). Consistent with the experimentally verified function. Reason: Correct core molecular function, mapped from EC 2.3.1.50 / RHEA:14761, which matches the experimentally established reaction. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt condensing L-serine and activated acyl-CoA
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: SPTLC2 is a single-pass endoplasmic reticulum membrane protein, consistent with SPT acting at the ER. Reason: Correct subcellular location, mapped from the UniProt subcellular location and supported by By-similarity and structural evidence. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Endoplasmic reticulum membrane
GO:0016740 transferase activity	IEA GO_REF:0000002	MODIFY	Summary: Generic transferase activity mapped from InterPro. This is a high-level parent of the specific serine C-palmitoyltransferase activity that is already annotated. Reason: Too general to be informative. The specific, correct molecular function (GO:0004758 serine C-palmitoyltransferase activity) is well established for this gene and should be used in its place. Proposed replacements: serine C-palmitoyltransferase activity Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt condensing L-serine and activated acyl-CoA
GO:0017059 serine palmitoyltransferase complex	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (ARBA) annotation that SPTLC2 is part of the serine palmitoyltransferase complex. Consistent with experimental and structural evidence. Reason: Correct and core; duplicates the well-supported IBA/IDA complex annotations. Supporting Evidence: PMID:33558761 which consists of catalytic components (SPTLC1
GO:0030170 pyridoxal phosphate binding	IEA GO_REF:0000002	ACCEPT	Summary: SPTLC2 binds the PLP cofactor required for catalysis; the catalytic lysine (Lys379) forms a Schiff base with PLP. Mapped from InterPro and consistent with the cofactor requirement and structural/mutagenesis data. Reason: Correct secondary molecular function. SPT is a PLP-dependent class-II aminotransferase; Lys379 is the PLP-binding N6-(pyridoxal phosphate)lysine, and K379A abolishes activity. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt N6-(pyridoxal phosphate)lysine file:human/SPTLC2/SPTLC2-uniprot.txt Name=pyridoxal 5'-phosphate;
GO:0046512 sphingosine biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: Electronic (ARBA) annotation to sphingoid base biosynthesis, consistent with the SPT catalytic role at the head of the pathway. Reason: Correct; duplicates the IBA/IDA sphingosine biosynthetic process annotations. Supporting Evidence: PMID:19416851 catalyzes the first committed step in
GO:0005515 protein binding	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	MARK AS OVER ANNOTATED	Summary: IntAct-derived binary interaction with SPTLC1 (O15269). The biologically meaningful capture of this interaction is membership in the serine palmitoyltransferase complex (GO:0017059), which is separately annotated. Reason: Bare 'protein binding' is uninformative and does not convey the specific function. The SPTLC1-SPTLC2 interaction forms the SPT catalytic core and is already captured by the more informative part_of serine palmitoyltransferase complex annotation. Retained (not removed) per policy on experimental IPI annotations. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and
GO:0005515 protein binding	IPI PMID:33558762 Structural insights into the assembly and substrate selectiv...	MARK AS OVER ANNOTATED	Summary: IntAct-derived binary interaction with SPTLC1 (O15269), from the SPT-ORMDL3 cryo-EM study. The informative capture is complex membership (GO:0017059). Reason: Uninformative bare 'protein binding'; the specific, informative annotation is part_of the serine palmitoyltransferase complex. Retained per policy. Supporting Evidence: PMID:33558762 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: IntAct-derived binary interaction with SPTLC1 (O15269) from the OpenCell endogenous tagging / IP-MS interactome dataset. Reason: Uninformative bare 'protein binding' from a high-throughput interactome; the specific SPTLC1 interaction is already better captured by part_of serine palmitoyltransferase complex. Retained per policy. Supporting Evidence: PMID:35271311 systematically map the localization and interactions of human proteins
GO:0030148 sphingolipid biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: Automatic transfer (Ensembl Compara) from mouse ortholog of the core biological process: de novo sphingolipid biosynthesis. Reason: Correct core biological process; SPT catalyzes the first, committed, rate-limiting step of de novo sphingolipid biosynthesis. Duplicates the IDA/TAS annotations. Supporting Evidence: PMID:33558762 rate-limiting step in the de novo biosynthesis of all sphingolipids
GO:0060612 adipose tissue development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transferred from mouse ortholog (P97363); SPT/de novo sphingolipid synthesis is reported to be important for adipogenesis. This is a peripheral, tissue-level developmental role, not the core molecular function. Reason: A By-similarity/orthology-transferred developmental process. Plausible but downstream of the enzyme's catalytic role and not a core SPTLC2 function; keep as non-core. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Crucial
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway mapping to the broad sphingolipid metabolic process. This is the parent of the more specific, and already-annotated, sphingolipid biosynthetic process. Reason: Not wrong, but less informative than the biosynthetic-process child term (GO:0030148), which is separately and better annotated. Keep as non-core parent. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Lipid metabolism; sphingolipid metabolism.
GO:0005789 endoplasmic reticulum membrane	NAS PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: ER membrane localization asserted from the structural study of the human SPT complex. Reason: Correct subcellular location; the SPT holocomplex is an ER-membrane complex. Duplicates other ER membrane annotations. Supporting Evidence: PMID:33558761 and rate-limiting step of sphingolipid synthesis is catalyzed by the serine
GO:0017059 serine palmitoyltransferase complex	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: ComplexPortal-curated membership of SPTLC2 in the serine palmitoyltransferase complex, based on the biochemical characterization of the SPT complex. Reason: Correct and core complex membership. SPTLC2 forms the catalytic core with SPTLC1. 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: ComplexPortal-curated membership of SPTLC2 in the SPT complex, based on the cryo-EM structures of the human SPT holocomplex. Reason: Correct and core complex membership, established by the SPT holocomplex structures. Supporting Evidence: PMID:33558761 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: SPT isozymes containing SPTLC2 produce long-chain (sphingoid) bases; SPTLC2 is required for sphingoid base biosynthesis. Reason: Correct; SPTLC2-containing SPT generates the sphingoid base backbone. Supported by long-chain base profiling of reconstituted isozymes. Supporting Evidence: PMID:19416851 differences in acyl-CoA preference
GO:0046512 sphingosine biosynthetic process	IDA PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: Structural/biochemical study of the human SPT holocomplex confirming its role in the de novo sphingolipid (sphingoid base) synthesis pathway. Reason: Correct; SPTLC2 within the SPT holocomplex catalyzes the committed step generating sphingoid bases. Supporting Evidence: PMID:33558761 and rate-limiting step of sphingolipid synthesis is catalyzed by the serine
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: ER membrane localization inferred by sequence similarity from mouse ortholog (P97363). Reason: Correct subcellular location; consistent with the ER-membrane SPT complex. Duplicates other ER membrane annotations. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Endoplasmic reticulum membrane
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct enzymatic characterization of reconstituted SPT isozymes containing SPTLC2, demonstrating serine C-palmitoyltransferase activity. contributes_to correctly reflects that catalysis is a property of the SPTLC1/SPTLC2 heterodimer. Reason: Core molecular function with direct experimental support and the strictly correct contributes_to qualifier for a subunit of a catalytic complex. Supporting Evidence: PMID:19416851 catalyzes the first committed step in
GO:0006686 sphingomyelin biosynthetic process	IDA PMID:30242129 Complex formation of sphingomyelin synthase 1 with glucosylc...	KEEP AS NON CORE	Summary: Sphingomyelin biosynthesis is a downstream branch of the sphingolipid pathway (ceramide -> sphingomyelin, at the Golgi, via SMS1). SPT provides the initial sphingoid base/ceramide precursor at the ER but does not itself synthesize sphingomyelin. Reason: Downstream pathway involvement rather than a direct/core SPTLC2 molecular role. The cited paper concerns the SMS1-GCS complex; SM synthesis depends on the de novo ceramide supplied by SPT (condensation of serine and palmitoyl-CoA in the ER). Keep as non-core. Supporting Evidence: PMID:30242129 cytosolic leaflet of the ER bilayer
GO:0046513 ceramide biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: SPTLC2-containing SPT initiates de novo synthesis of the sphingoid base that is converted to ceramide by downstream enzymes. Reason: Correct; ceramide biosynthesis is initiated by the SPT step catalyzed by SPTLC1/SPTLC2. Supporting Evidence: PMID:19416851 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: Glycosphingolipids are downstream products of the sphingolipid pathway; the sphingoid bases generated by SPT feed into glycosphingolipid synthesis. Reason: Downstream branch of the pathway rather than a direct SPTLC2 function. SPT supplies the long-chain-base precursor; glycosphingolipid-specific steps are catalyzed by other enzymes. Keep as non-core. Supporting Evidence: PMID:19416851 differences in acyl-CoA preference
GO:0017059 serine palmitoyltransferase complex	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct identification of SPTLC2 in the SPT complex. Reason: Correct and core complex membership; duplicates other well-supported complex annotations. 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: SPT acts on the cytosolic face of the ER membrane, where de novo sphingolipid synthesis is initiated by condensation of L-serine and palmitoyl-CoA. Reason: Correct and appropriately specific location of activity; the initial condensation step occurs on the cytoplasmic/cytosolic leaflet of the ER. Supporting Evidence: PMID:30242129 cytosolic leaflet of the ER bilayer
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	ACCEPT	Summary: Study of de novo sphingolipid synthesis via SPT (mouse liver); serine C-palmitoyltransferase activity is the SPT function, with SPTLC2 contributing to the catalytic heterodimer. Reason: Correct core molecular function with the appropriate contributes_to qualifier. Supporting Evidence: PMID:25332431 overexpression of serine palmitoyltransferase to elevate de novo sphingolipid
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-428127	ACCEPT	Summary: Reactome traceable assertion placing the SPTLC complexes / acyl-CoA transfer onto serine at the ER membrane. Reason: Correct subcellular location; consistent with all other ER-membrane evidence. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Endoplasmic reticulum membrane
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:26573920 The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Heredi...	ACCEPT	Summary: Study of the HSAN1C variant p.(Arg183Trp) demonstrating SPT catalytic activity of SPTLC2 and its alteration by the disease variant (increased 1-deoxysphingolipid formation). Reason: Correct core molecular function, supported by in vitro activity measurements of WT vs variant SPTLC2. Supporting Evidence: PMID:26573920 produced elevated amounts of 1-deoxysphingolipids in vitro
GO:0030148 sphingolipid biosynthetic process	IDA PMID:26573920 The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Heredi...	ACCEPT	Summary: SPTLC2 is directly implicated in de novo sphingolipid biosynthesis; the disease variant perturbs the pathway output (accumulation of 1-deoxysphingolipids). Reason: Correct core biological process, supported by direct metabolite measurements. Supporting Evidence: PMID:26573920 produced elevated amounts of 1-deoxysphingolipids in vitro
GO:0060612 adipose tissue development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Inferred by sequence similarity from mouse ortholog (P97363); a peripheral tissue-level developmental role attributed to SPT/de novo sphingolipid synthesis. Reason: By-similarity developmental process; downstream of and secondary to the catalytic function. Keep as non-core. Supporting Evidence: file:human/SPTLC2/SPTLC2-uniprot.txt Crucial
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: SPT (with SPTLC2 in the catalytic core) catalyzes the initiating step of sphingolipid biosynthesis; this study examines ORMDL/SPT stoichiometry and its effect on that activity. Reason: Correct core molecular function with the appropriate contributes_to qualifier for a subunit of the catalytic complex. Supporting Evidence: PMID:25691431 negative homeostatic regulators of the initiating
GO:0046513 ceramide biosynthetic process	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: SPT activity (initiating step) acts upstream of ceramide biosynthesis; modulating ORMDL/SPT stoichiometry affects downstream sphingolipid (ceramide) production. Reason: Correct; SPTLC2 acts upstream of ceramide biosynthesis by generating the sphingoid base precursor. acts_upstream_of_or_within is an appropriate causal qualifier here. Supporting Evidence: PMID:25691431 negative homeostatic regulators of the initiating
GO:1904504 positive regulation of lipophagy	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	KEEP AS NON CORE	Summary: In mouse liver, overexpression of SPT to elevate de novo sphingolipid synthesis induced autophagy. This links elevated SPT/sphingolipid flux to autophagy/lipophagy, but is an indirect, downstream physiological consequence rather than a direct SPTLC2 function. Reason: Indirect regulatory effect via elevated sphingolipid/ceramide levels, from a mouse-liver overexpression study; not a direct molecular role of SPTLC2. Keep as non-core. Supporting Evidence: PMID:25332431 induces autophagy in the liver
GO:0030148 sphingolipid biosynthetic process	IDA PMID:25332431 Autophagy regulates sphingolipid levels in the liver.	ACCEPT	Summary: SPT activity (with SPTLC2) drives de novo sphingolipid biosynthesis; overexpression elevates de novo sphingolipid production in liver. Reason: Correct core biological process. acts_upstream_of_or_within is a valid causal qualifier for the enzyme initiating the pathway. Supporting Evidence: PMID:25332431 overexpression of serine palmitoyltransferase to elevate de novo sphingolipid
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:20920666 Mutations in the SPTLC2 subunit of serine palmitoyltransfera...	ACCEPT	Summary: Characterization of HSAN1C variants (V359M, G382V, I504F) demonstrating that SPTLC2 supplies SPT catalytic activity, with disease variants causing partial-to-complete loss of normal activity and accumulation of 1-deoxysphinganine. Reason: Correct core molecular function, supported by in vitro/in vivo activity measurements of WT vs disease-variant SPTLC2. Supporting Evidence: PMID:20920666 atypical and neurotoxic sphingoid metabolite 1-deoxy-sphinganine
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct enzymatic assay of reconstituted SPT isozymes containing SPTLC2 establishing serine C-palmitoyltransferase activity. Reason: Core molecular function with direct experimental support. Supporting Evidence: PMID:19416851 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 SPTLC2-containing SPT functions in de novo sphingolipid biosynthesis. Reason: Correct core biological process; duplicates the IDA/IEA sphingolipid biosynthetic process annotations. Supporting Evidence: PMID:19416851 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: Original cloning/characterization paper establishing that the human/murine LCB2 genes encode serine palmitoyltransferase, the PLP-dependent enzyme condensing L-serine and palmitoyl-CoA to 3-oxosphinganine. Reason: Correct core molecular function; foundational traceable assertion for SPTLC2 catalytic activity. Supporting Evidence: PMID:9363775 It catalyzes the pyridoxal-5'-phosphate-dependent condensation of PMID:9363775 the human and murine LCB2 genes

Gene Description

Existing Annotations Review

Core Functions

Pyridoxal 5'-phosphate binding: SPTLC2 binds the PLP cofactor essential for catalysis via the catalytic Lys379 that forms a Schiff base with PLP.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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