SPTSSA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004758 serine C-palmitoyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred contribution to serine C-palmitoyltransferase activity as a subunit of the SPT complex. SPTSSA is a non-catalytic accessory subunit that is required for full activity of the catalytic SPTLC1-SPTLC2/3 core, so the contributes_to qualifier is exactly right. Reason: SPTSSA is an accessory subunit that stimulates and shapes SPT catalysis but does not independently catalyze the reaction; the IBA contributes_to annotation captures this correctly and is supported by biochemistry and structural biology. Supporting Evidence: PMID:19416851 each substantially enhance the activity of mammalian SPT PMID:33558762 SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity
GO:0017059 serine palmitoyltransferase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred membership in the serine palmitoyltransferase complex. Cryo-EM structures directly place SPTSSA in the human SPT holocomplex with SPTLC1, SPTLC2 (or SPTLC3) and ORMDL3. Reason: SPTSSA is a bona fide subunit of the SPT complex, confirmed by multiple cryo-EM structures and ComplexPortal (CPX-6663, CPX-6665). The GO definition of GO:0017059 explicitly lists SPTSSA/SPTSSB as regulatory activator components. Supporting Evidence: PMID:33558762 SPTLC1 and SPTLC2 form a dimer of heterodimers as the catalytic core PMID:33558761 ssSPTa engages SPTLC2 and shapes the tunnel
GO:0046513 ceramide biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetically inferred involvement in ceramide biosynthesis. SPT catalyzes the first committed step upstream of ceramide, so SPTSSA (as an SPT subunit) contributes upstream to ceramide production, but ceramide synthesis itself requires several additional dedicated enzymes. Reason: SPTSSA acts only at the first step of sphingolipid biosynthesis; ceramide is a downstream product requiring 3-ketodihydrosphingosine reductase and ceramide synthases. The involvement is real but indirect, so this is best kept as a non-core downstream process, with sphingolipid biosynthetic process (GO:0030148) as the core BP. Supporting Evidence: PMID:37308477 catalyzes the first and rate-limiting step of de novo sphingolipid biosynthesis by condensation of serine and palmitoyl-CoA to generate 3-keto-dihydrosphingosine
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation to ER membrane from the UniProt subcellular-location mapping. SPTSSA is a multi-pass ER membrane protein, experimentally confirmed. Reason: Consistent with the experimental subcellular location (PubMed:23510452) and with the SPT complex residing in the ER membrane. The IEA mapping is correct. Supporting Evidence: file:human/SPTSSA/SPTSSA-uniprot.txt SUBCELLULAR LOCATION Endoplasmic reticulum membrane
GO:0005515 protein binding	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation supported by interaction with SPTLC1 (UniProtKB:O15269), the catalytic-core subunit of SPT. This is a biologically meaningful interaction, but the bare protein binding term is uninformative. Reason: The SPTSSA-SPTLC1 interaction is real and important, but GO:0005515 protein binding conveys no functional information. The meaningful content (SPT complex membership) is already captured by GO:0017059. Per curation policy the annotation is retained rather than removed, but flagged as an uninformative over-annotation. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotations from the HuRI human binary interactome map (CYSRT1, GET1, HERPUD2, RHBDL1). These are high-throughput yeast two-hybrid hits of uncertain physiological significance for this ER membrane protein. Reason: Bare protein binding is uninformative and these are large-scale binary-screen hits with no established functional consequence for SPTSSA. Retained per policy but flagged; not used for core function. Supporting Evidence: PMID:32296183 a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'
GO:0005515 protein binding	IPI PMID:33558762 Structural insights into the assembly and substrate selectiv...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation supported by the cryo-EM structure showing SPTSSA (SPTssa) as a subunit engaging the SPTLC1/SPTLC2 catalytic core within the SPT-ORMDL3 complex. Reason: The physical association is genuine and structurally defined, but the bare protein binding term is uninformative; the functional content is captured by SPT complex membership (GO:0017059) and the contributes_to catalytic annotation. Retained per policy but flagged. Supporting Evidence: PMID:33558762 SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000041	ACCEPT	Summary: Electronic annotation to sphingolipid metabolic process from the UniPathway mapping. SPTSSA participates in de novo sphingolipid metabolism as an SPT subunit. Reason: Correct but general parent process of the more specific sphingolipid biosynthetic process; consistent with SPT function at the first step of the pathway. Supporting Evidence: file:human/SPTSSA/SPTSSA-uniprot.txt PATHWAY Lipid metabolism; sphingolipid metabolism
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct-assay annotation of serine C-palmitoyltransferase activity from the original functional characterization, where reconstituted SPT isozymes containing ssSPTa were assayed for enzyme activity and acyl-CoA preference. The activity is a property of the assembled complex; SPTSSA is the accessory subunit required for full activity. Reason: The reconstituted SPT isozyme assay (with ssSPTa) demonstrates the complex-level palmitoyltransferase activity. Since SPTSSA is non-catalytic, the contributes_to form is more precise, but this enables IDA (from a curator who read the full text) is retained as reflecting the assayed complex activity. Supporting Evidence: PMID:19416851 each substantially enhance the activity of mammalian SPT
GO:0005789 endoplasmic reticulum membrane	NAS PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: Non-traceable-author-statement annotation (ComplexPortal) placing SPTSSA in the ER membrane, consistent with the SPT holocomplex residing in the ER. Reason: Consistent with the experimentally established ER membrane localization and with the structural work on the ER-resident SPT complex. Supporting Evidence: PMID:33558761 the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex
GO:0017059 serine palmitoyltransferase complex	IPI PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: SPT complex membership demonstrated by the original identification of ssSPTa as an SPT subunit that interacts with hLCB1 (SPTLC1) and hLCB2 (SPTLC2) and forms part of the SPT holoenzyme. Reason: Well-supported experimental annotation of complex membership; SPTSSA is a core structural component of SPT. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis
GO:0017059 serine palmitoyltransferase complex	IPI PMID:33558761 Structural insights into the regulation of human serine palm...	ACCEPT	Summary: SPT complex membership demonstrated by cryo-EM structures of the human SPT holocomplex containing ssSPTa together with SPTLC1, SPTLC2 and ORMDL3. Reason: Directly supported by high-resolution structures of the assembled complex. Supporting Evidence: PMID:33558761 the serine palmitoyltransferase holocomplex, which consists of catalytic components (SPTLC1 and SPTLC2) and regulatory components (ssSPTa and ORMDL3)
GO:0046512 sphingosine biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	KEEP AS NON CORE	Summary: Involvement in sphingosine biosynthesis via the SPT-catalyzed first committed step. Sphingosine is a downstream product formed after several additional enzymatic steps. Reason: SPTSSA contributes upstream (first step of the pathway) but sphingosine formation requires multiple downstream enzymes; keep as a non-core downstream process rather than the core function. Supporting Evidence: PMID:37308477 condensation of serine and palmitoyl-CoA to generate 3-keto-dihydrosphingosine
GO:0046512 sphingosine biosynthetic process	IDA PMID:33558761 Structural insights into the regulation of human serine palm...	KEEP AS NON CORE	Summary: Second IDA annotation (ComplexPortal) for involvement in sphingosine biosynthesis via the ER SPT complex characterized structurally in this paper. Reason: As above, involvement is upstream and indirect; retained as a non-core downstream process. Supporting Evidence: PMID:33558761 the first and rate-limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase holocomplex
GO:0005789 endoplasmic reticulum membrane	EXP PMID:23510452 Identification of small subunit of serine palmitoyltransfera...	ACCEPT	Summary: Experimental localization of ssSPTa to the ER membrane. This is the anchor experimental annotation supporting the ER membrane localization propagated by other evidence codes. Reason: Directly demonstrated experimentally; SPTSSA is a multi-pass ER membrane protein. Supporting Evidence: file:human/SPTSSA/SPTSSA-uniprot.txt SUBCELLULAR LOCATION Endoplasmic reticulum membrane
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Direct-assay annotation with the contributes_to qualifier, accurately capturing that SPTSSA contributes to, but does not independently enable, the serine C-palmitoyltransferase activity of the SPT complex. Reason: This is the most precise molecular-function annotation for SPTSSA, a non-catalytic accessory subunit that is required for full SPT activity and sets acyl-CoA specificity. Selected as the core molecular-function evidence. Supporting Evidence: PMID:19416851 each substantially enhance the activity of mammalian SPT PMID:33558762 SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity
GO:0006686 sphingomyelin biosynthetic process	IDA PMID:30242129 Complex formation of sphingomyelin synthase 1 with glucosylc...	MARK AS OVER ANNOTATED	Summary: IDA annotation to sphingomyelin biosynthetic process citing PMID:30242129. That paper is about the SMS1-GCS (sphingomyelin synthase 1 / glucosylceramide synthase) heteromeric complex controlling the metabolic fate of ceramide in the Golgi; SPTSSA/ssSPTa is not mentioned anywhere in the full text. Reason: The cited full-text paper does not study SPTSSA, and sphingomyelin synthesis is a distant downstream Golgi process (SM synthase acts on ceramide many steps after SPT). This is an over-annotation. Per curation policy for experimental annotations it is flagged rather than removed, but it should not be treated as a function of SPTSSA. Supporting Evidence: PMID:30242129 Sphingomyelin synthase 1 (SMS1) and glucosylceramide synthase (GCS) are key enzymes that catalyze the conversion of Cer to SM and GlcCer
GO:0046513 ceramide biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	KEEP AS NON CORE	Summary: IDA involvement in ceramide biosynthesis via the SPT first committed step characterized in the original ssSPTa paper. Reason: Involvement is upstream and indirect (ceramide requires downstream reductase and ceramide synthases); retained as a non-core downstream process, with sphingolipid biosynthetic process as the core BP. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis
GO:0006688 glycosphingolipid biosynthetic process	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	KEEP AS NON CORE	Summary: IDA involvement in glycosphingolipid biosynthesis via the SPT first committed step. Glycosphingolipids are far-downstream products built on glucosylceramide. Reason: SPTSSA contributes only at the pathway entry point; glycosphingolipid synthesis requires many additional, dedicated glycosyltransferases. Retained as a non-core downstream process. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis
GO:0017059 serine palmitoyltransferase complex	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: IDA SPT complex membership from the original ssSPTa identification, where ssSPTa was shown to be part of the SPT holoenzyme and to interact with both catalytic subunits. Reason: Well-supported experimental complex-membership annotation. Supporting Evidence: PMID:19416851 each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis
GO:0098554 cytoplasmic side of endoplasmic reticulum membrane	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Localization to the cytoplasmic face of the ER membrane, consistent with the SPT catalytic reaction (condensation of L-serine and cytosolic palmitoyl-CoA) occurring on the cytosolic leaflet of the ER, and with the SPTSSA topology (both termini cytoplasmic). Reason: Consistent with SPTSSA membrane topology (cytoplasmic N- and C-termini, two TM helices) and with the cytosolic-leaflet site of SPT catalysis. Supporting Evidence: PMID:30242129 Cer is synthesized de novo in the cytosolic leaflet of the ER bilayer by sequential enzyme reactions that are initiated by the condensation of serine and palmitoyl-CoA file:human/SPTSSA/SPTSSA-uniprot.txt TOPO_DOM 58..71
GO:0005515 protein binding	IPI PMID:23510452 Identification of small subunit of serine palmitoyltransfera...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation supported by interaction with MBOAT7/LPIAT1 (UniProtKB:Q96N66). This is a functionally meaningful, SPT-independent interaction relevant to MBOAT7 localization, but the bare protein binding term is uninformative. Reason: The MBOAT7 interaction is genuine and biologically interesting, but GO:0005515 protein binding is uninformative; the functional content is better captured by the intracellular protein localization (GO:0008104) annotation. Retained per policy but flagged. Supporting Evidence: PMID:23510452 ssSPTa co-immunoprecipitated and colocalized with LPIAT1 in cultured mammalian cells
GO:0005783 endoplasmic reticulum	IDA PMID:23510452 Identification of small subunit of serine palmitoyltransfera...	ACCEPT	Summary: Direct-assay localization to the endoplasmic reticulum, the parent compartment of the more specific ER membrane annotation. Reason: Correct; consistent with the experimentally established ER membrane localization of this multi-pass membrane protein. Supporting Evidence: file:human/SPTSSA/SPTSSA-uniprot.txt SUBCELLULAR LOCATION Endoplasmic reticulum membrane
GO:0008104 intracellular protein localization	IDA PMID:23510452 Identification of small subunit of serine palmitoyltransfera...	KEEP AS NON CORE	Summary: Involvement in intracellular protein localization, reflecting ssSPTa's SPT-independent role in facilitating MBOAT7/LPIAT1 localization to mitochondria-associated ER membranes (MAM). Knockdown of ssSPTa reduced LPIAT1 protein in the crude mitochondrial fraction and reduced LPIAT1-dependent incorporation of arachidonic acid into phosphatidylinositol. Reason: This is a genuine secondary, SPT-independent function of SPTSSA supported by experimental data, but it is distinct from and subordinate to its core role in sphingolipid biosynthesis as an SPT subunit. Supporting Evidence: PMID:23510452 facilitating the MAM localization of LPIAT1
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-428127	ACCEPT	Summary: Traceable-author-statement (Reactome) localization to the ER membrane, consistent with all other localization evidence. Reason: Consistent with the experimental ER membrane localization and the Reactome sphingolipid de novo biosynthesis pathway in which SPT acts. Supporting Evidence: file:human/SPTSSA/SPTSSA-uniprot.txt SUBCELLULAR LOCATION Endoplasmic reticulum membrane
GO:0004758 serine C-palmitoyltransferase activity	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	ACCEPT	Summary: IDA annotation of serine C-palmitoyltransferase activity assigned by MGI citing PMID:25691431, a study of ORMDL/SPT stoichiometry and its effect on sphingolipid biosynthesis. The complex-level SPT activity assayed there depends on the ssSPTa-containing SPT complex. Reason: The paper assays SPT enzyme activity in the context of the SPT-ORMDL complex, which contains ssSPTa; the curator (MGI) had access to the full text. As for the other GO:0004758 entries, the contributes_to form is more precise for this non-catalytic subunit, but the annotation reflects real complex activity and is retained. Supporting Evidence: PMID:25691431 negative homeostatic regulators of the initiating enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT)
GO:0046513 ceramide biosynthetic process	IDA PMID:25691431 ORMDL/serine palmitoyltransferase stoichiometry determines e...	KEEP AS NON CORE	Summary: Involvement in ceramide biosynthesis (acts_upstream_of_or_within) via the SPT-catalyzed entry step, assigned by MGI citing the ORMDL3/SPT stoichiometry study. Reason: SPTSSA acts upstream of ceramide as the entry point of the pathway; the acts_upstream_of_or_within qualifier is appropriate, but this downstream process is non-core relative to the sphingolipid biosynthetic process. Supporting Evidence: PMID:25691431 the initiating enzyme in sphingolipid biosynthesis, serine palmitoyltransferase (SPT)
GO:0030148 sphingolipid biosynthetic process	TAS PMID:19416851 Identification of small subunits of mammalian serine palmito...	ACCEPT	Summary: Traceable-author-statement involvement in sphingolipid biosynthetic process. This is the core biological process for SPTSSA; as an SPT subunit it participates in the first, rate-limiting step of de novo sphingolipid biosynthesis. Reason: This is the most accurate and appropriately general BP for SPTSSA, directly reflecting its role in the SPT complex at the entry point of sphingolipid biosynthesis. Selected as the core biological process. Supporting Evidence: PMID:19416851 Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis
GO:0008047 enzyme activator activity	IDA PMID:19416851 Identification of small subunits of mammalian serine palmito...	NEW	Summary: Proposed molecular function capturing the subunit-specific role of SPTSSA as a non-catalytic activator of the SPT complex. SPTSSA (ssSPTa) is not itself a transferase; rather, it binds the SPTLC1-SPTLC2 catalytic core, is required for full SPT activity, and stimulates catalysis while setting acyl-CoA substrate specificity. This is more informative about SPTSSA's own function than the complex-level catalytic term (GO:0004758), which SPTSSA only contributes to. Reason: SPTSSA is an accessory activator subunit; enzyme activator activity (a molecular-function regulator that increases a catalytic activity) precisely describes its distinct role, complementing the contributes_to serine C-palmitoyltransferase activity annotation. Supported by biochemistry (activity enhancement) and structural biology (engaging SPTLC2 and shaping the substrate tunnel). Supporting Evidence: PMID:19416851 each substantially enhance the activity of mammalian SPT PMID:33558762 SPTssa participates in acyl-CoA coordination, thereby stimulating the SPT activity and regulating the substrate selectivity

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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