Dpl1 is the sphingoid long-chain base 1-phosphate lyase of Saccharomyces cerevisiae, a pyridoxal 5'-phosphate-dependent enzyme anchored in the endoplasmic reticulum membrane by a single N-terminal transmembrane segment and active as an oligomer. It irreversibly cleaves phosphorylated sphingoid bases (dihydrosphingosine-1-phosphate, preferred, and phytosphingosine-1-phosphate) at the C2-C3 bond into a long-chain fatty aldehyde (hexadecanal or 2-hydroxyhexadecanal) and phosphoethanolamine (EC 4.1.2.27). This is the only exit route from sphingolipid metabolism: it controls cellular levels of long-chain base phosphates, which act as signals, and channels phytosphingosine into odd-chain fatty acids that are incorporated into glycerophospholipids. dpl1 mutants accumulate long-chain base phosphates, are sensitive to exogenous sphingoid bases, and show altered nutrient-deprivation and Ca2+ signalling responses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005777 peroxisome | HDA PMID:35563734 Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulati... | KEEP AS NON CORE | Summary: HDA from a peroxisomal proteomics study (Pls1 paper, 2022); Dpl1 is not discussed in the main text. Dpl1 is an established integral ER membrane protein; peroxisomal detection is probably contamination or a minor pool. Reason: Proteomic detection not supported by targeted localisation. Supporting Evidence: PMID:35563734 Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulating Lysine Biosynthesis. |
| GO:0005783 endoplasmic reticulum | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the genome-wide GFP localisation screen (Huh et al. 2003) placing Dpl1 in the ER. Consistent with targeted studies. Supporting Evidence: PMID:18487605 confirm it as an integral endoplasmic reticulum-resident protein |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000242650) is_active_in ER, from human SGPL1, mouse Sgpl1, Arabidopsis DPL1 and Dpl1 itself. Correct. Supporting Evidence: PMID:18487605 confirm it as an integral endoplasmic reticulum-resident protein |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:18487605 Identifying key residues of sphinganine-1-phosphate lyase fo... | ACCEPT | Summary: EXP (Mukhopadhyay et al. 2008) - Dpl1 is an integral ER-resident membrane protein. Supporting Evidence: PMID:18487605 confirm it as an integral endoplasmic reticulum-resident protein |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0097, ER membrane). Correct. Supporting Evidence: PMID:18487605 confirm it as an integral endoplasmic reticulum-resident protein |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA placing the lyase reaction of SPHINGOLIPID-SYN-PWY-1 in the cytosol (pathway default). Dpl1 is an integral ER membrane protein, not a soluble cytosolic enzyme. Reason: Pathway-default compartment contradicted by the established ER membrane localisation. Supporting Evidence: PMID:18487605 confirm it as an integral endoplasmic reticulum-resident protein |
| GO:0006665 sphingolipid metabolic process | IEA GO_REF:0000041 | TOO GENERAL | Summary: UniPathway IEA (UPA00222 sphingolipid metabolism). Correct but general. Supporting Evidence: PMID:9334171 Sphingosine 1-phosphate degradation requires cleavage at the C2-3 carbon bond by sphingosine phosphate lyase. |
| GO:0006665 sphingolipid metabolic process | IMP PMID:9334171 The BST1 gene of Saccharomyces cerevisiae is the sphingosine... | TOO GENERAL | Summary: IMP (Saba et al. 1997) - bst1/dpl1 deletion causes sphingoid-base sensitivity and S1P accumulation. Supporting Evidence: PMID:9334171 BST1 deletion produced sensitivity to exogenous D-erythro-sphingosine and phytosphingosine and intracellular accumulation of sphingosine 1-phosphate upon exposure to exogenous sphingosine. |
| GO:0008117 sphinganine-1-phosphate aldolase activity | EXP PMID:20696404 Structure and function of sphingosine-1-phosphate lyase, a k... | ACCEPT | Summary: EXP (Bourquin et al. 2010) - structural and in vitro/in vivo functional characterisation of Dpl1 SPL activity and active-site residues. Core activity. Supporting Evidence: PMID:20696404 We structurally and functionally characterized yeast SPL (Dpl1p) |
| GO:0008117 sphinganine-1-phosphate aldolase activity | EXP PMID:25345524 Identification of the phytosphingosine metabolic pathway lea... | ACCEPT | Summary: EXP (Kondo et al. 2014) - Dpl1 lyase activity on DHS-1-P and PHS-1-P with kinetic constants; committed step of phytosphingosine catabolism. Supporting Evidence: PMID:25345524 long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids |
| GO:0008117 sphinganine-1-phosphate aldolase activity | EXP PMID:9464245 Identification of the first mammalian sphingosine phosphate ... | ACCEPT | Summary: EXP from Zhou & Saba 1998 (mouse SPL cloning, which used the yeast dpl1/bst1 deletion and yeast SPL as reference). Cited by UniProt for the Dpl1 reaction; curator judgment deferred to. Supporting Evidence: PMID:9464245 Expression of the mouse SPL gene in a yeast strain-delta bst1, which carries a deletion of the SPL gene and is hypersensitive to sphingosine, restored a sphingosine-resistant phenotype |
| GO:0008117 sphinganine-1-phosphate aldolase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000242650) for sphinganine-1-phosphate aldolase activity, seeded by SPLs from human, mouse, fly, plant, trypanosomatids and Dpl1. Correct. Supporting Evidence: PMID:9334171 A yeast genetic approach was used to clone the first sphingosine phosphate lyase gene, BST1. |
| GO:0008117 sphinganine-1-phosphate aldolase activity | IDA PMID:9334171 The BST1 gene of Saccharomyces cerevisiae is the sphingosine... | ACCEPT | Summary: IDA (Saba et al. 1997) for SPL activity of BST1/DPL1. Supporting Evidence: PMID:9334171 A yeast genetic approach was used to clone the first sphingosine phosphate lyase gene, BST1. |
| GO:0008117 sphinganine-1-phosphate aldolase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (RHEA:18593, EC 4.1.2.27). Correct. Supporting Evidence: file:yeast/DPL1/DPL1-uniprot.txt Reaction=sphinganine 1-phosphate = hexadecanal + phosphoethanolamine; |
| GO:0008117 sphinganine-1-phosphate aldolase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (sphinganine-1-P -> palmitaldehyde + phosphoethanolamine). Correct MF. Supporting Evidence: file:yeast/DPL1/DPL1-uniprot.txt Reaction=sphinganine 1-phosphate = hexadecanal + phosphoethanolamine; |
| GO:0009267 cellular response to starvation | IMP PMID:10329480 The DPL1 gene is involved in mediating the response to nutri... | KEEP AS NON CORE | Summary: IMP (Gottlieb et al. 1999) - dpl1 cells accumulate phosphorylated sphingoid bases and fail to arrest properly in G1 on nutrient deprivation. Indirect consequence of altered LCB-phosphate levels. Reason: Physiological consequence of substrate accumulation, not the enzymatic core. Supporting Evidence: PMID:10329480 implicate a role for DPL1 and phosphorylated sphingoid bases in the regulation of global responses to nutrient deprivation in yeast |
| GO:0016830 carbon-carbon lyase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR002129, PLP-dependent decarboxylase/lyase domain) for carbon-carbon lyase activity. Correct parent of the specific SPL activity. Supporting Evidence: PMID:9334171 Sphingosine 1-phosphate degradation requires cleavage at the C2-3 carbon bond by sphingosine phosphate lyase. |
| GO:0019722 calcium-mediated signaling | IMP PMID:11278643 Calcium influx and signaling in yeast stimulated by intracel... | KEEP AS NON CORE | Summary: IMP (Birchwood et al. 2001) - Dpl1 (with Lcb3) limits S1P-triggered Cch1/Mid1-dependent Ca2+ influx; dpl1 lcb3 mutants show constitutive Ca2+ signalling. Dpl1 acts by degrading the signalling lipid, an indirect, negative-regulatory role. Reason: Indirect effect through removal of the S1P-like signal. Supporting Evidence: PMID:11278643 was inhibited by the functions of S1P lyase (Dpl1p) and the S1P phosphatase (Lcb3p) |
| GO:0030148 sphingolipid biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA inherited from the yeast sphingolipid biosynthesis pathway (SPHINGOLIPID-SYN-PWY-1). Dpl1 irreversibly degrades long-chain base phosphates to fatty aldehyde and phosphoethanolamine, the exit step of sphingolipid metabolism; it does not build sphingolipids. Reason: Superpathway-inherited biosynthetic BP on a degradative enzyme; the correct process is sphingolipid catabolism. Proposed replacements: sphingolipid catabolic process Supporting Evidence: PMID:18487605 catalyzes the irreversible degradation of sphingoid base phosphates |
| GO:0030149 sphingolipid catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000242650) for sphingolipid catabolic process. Correct; the core process. Supporting Evidence: PMID:18487605 catalyzes the irreversible degradation of sphingoid base phosphates |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA for pyridoxal phosphate binding. Dpl1 is a PLP-dependent lyase (cofactor shown experimentally); correct cofactor-level annotation. Supporting Evidence: file:yeast/DPL1/DPL1-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; |
| GO:0032541 cortical endoplasmic reticulum | IDA PMID:18487605 Identifying key residues of sphinganine-1-phosphate lyase fo... | ACCEPT | Summary: IDA (Mukhopadhyay et al. 2008) - Dpl1 localises to cortical ER, part of its general ER distribution. Supporting Evidence: PMID:18487605 Results further indicate that Dpl1p is most likely not regulated spatially. |
| GO:0042802 identical protein binding | IPI PMID:20696404 Structure and function of sphingosine-1-phosphate lyase, a k... | KEEP AS NON CORE | Summary: IPI (Bourquin et al. 2010) for self-interaction; Dpl1 forms a dimer like other fold-type I PLP enzymes (oligomerisation also shown by Mukhopadhyay et al. 2008). Reason: Structural homo-oligomerisation required for PLP-enzyme architecture; not a separate function. Supporting Evidence: PMID:18487605 we demonstrate that Dpl1p exists as an oligomer |
| GO:0097038 perinuclear endoplasmic reticulum | IDA PMID:18487605 Identifying key residues of sphinganine-1-phosphate lyase fo... | ACCEPT | Summary: IDA (Mukhopadhyay et al. 2008) - perinuclear (nuclear envelope) ER localisation of Dpl1, together with cortical ER. Supporting Evidence: PMID:18487605 Results further indicate that Dpl1p is most likely not regulated spatially. |
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