Lac1 is one of two redundant catalytic subunits (with its paralog Lag1) of the acyl-CoA-dependent ceramide synthase of Saccharomyces cerevisiae, a TLC-domain multipass protein of the endoplasmic reticulum membrane. Together with the essential small subunit Lip1, Lac1 transfers very-long-chain (mainly C26:0) acyl groups from acyl-CoA onto the sphingoid bases dihydrosphingosine and phytosphingosine, forming dihydroceramide and phytoceramide (EC 2.3.1.297/2.3.1.24); the activity is fumonisin B1- and australifungin-sensitive. Loss of both LAC1 and LAG1 abolishes acyl-CoA-dependent ceramide synthesis, lowers complex sphingolipid levels, impairs ceramide remodelling of GPI anchors and slows ER-to-Golgi transport of GPI-anchored proteins. Ceramide made by this synthase is also needed for mating: haploid cells unable to synthesise ceramide fail to arrest in G1 in response to pheromone, are defective in pheromone-induced MAP kinase-dependent transcription and PI(4,5)P2 polarisation, and fail to localise the Ste5 scaffold to the plasma membrane.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | REMOVE | Summary: IPI (Vallee & Riezman 2005) with Lag1 (P38703) from co-purification of the ceramide synthase complex. Real association, represented by acyl-CoA ceramide synthase complex membership (GO:0061576). Reason: Uninformative 'protein binding' (the interaction is real); captured by GO:0061576. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0005515 protein binding | IPI PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | REMOVE | Summary: IPI (Vallee & Riezman 2005) with Lip1 (Q03579), the third ceramide synthase subunit. Captured by complex membership. Reason: Uninformative 'protein binding'; captured by GO:0061576. Supporting Evidence: PMID:15692566 SDS-PAGE analysis of purified ceramide synthase revealed the presence of a novel subunit of the enzyme, Lip1p. |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | REMOVE | Summary: IPI from a large-scale split-ubiquitin membrane interactome (Miller et al. 2005) with Lag1. Corroborates the ceramide synthase complex. Reason: Uninformative 'protein binding'; captured by GO:0061576. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: IPI from the PCA in vivo interactome (Tarassov et al. 2008) with Lag1. Corroborates the complex. Reason: Uninformative 'protein binding'; captured by GO:0061576. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI from a proteome-wide interactome (Michaelis et al. 2023) with Lag1. Corroborates the complex. Reason: Uninformative 'protein binding'; captured by GO:0061576. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: IPI from the same 2023 interactome with Lip1. Corroborates the complex. Reason: Uninformative 'protein binding'; captured by GO:0061576. Supporting Evidence: PMID:15692566 SDS-PAGE analysis of purified ceramide synthase revealed the presence of a novel subunit of the enzyme, Lip1p. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000285423) is_active_in ER, from mammalian CERS1-6, plant LOH1-3, S. pombe and yeast Lag1. Correct. Supporting Evidence: PMID:10198056 Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. |
| GO:0005783 endoplasmic reticulum | IDA PMID:10198056 Two endoplasmic reticulum (ER) membrane proteins that facili... | ACCEPT | Summary: IDA (Barz & Walter 1999) - immunofluorescence localises Lac1 (Dgt1) to the ER. Supporting Evidence: PMID:10198056 Both proteins are localized to the ER, as demonstrated by immunofluorescence microscopy. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0097 ER membrane). Correct for this multipass protein. Supporting Evidence: PMID:10198056 encoding structurally related proteins with multiple membrane-spanning domains |
| GO:0006665 sphingolipid metabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway IEA (UPA00222 sphingolipid metabolism). Correct, general. Supporting Evidence: PMID:11694577 lag1 Ξ lac1 Ξ cells have reduced sphingolipid levels due to a block of the fumonisin B1-sensitive and acyl-CoAβdependent ceramide synthase reaction |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR006634, TLC domain) for membrane. Correct, general. Supporting Evidence: PMID:10198056 encoding structurally related proteins with multiple membrane-spanning domains |
| GO:0034399 nuclear periphery | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: HDA from the SWAT-GFP library for nuclear periphery. Consistent with nuclear-envelope ER, which is continuous with the ER where Lac1 resides; not a distinct functional site. Reason: High-throughput localisation reflecting the perinuclear ER. Supporting Evidence: PMID:26928762 One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy. |
| GO:0046513 ceramide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000285423) for ceramide biosynthetic process. Correct. Supporting Evidence: PMID:11694577 LAG1 and LAC1 are the first genes to be identified that are required for the fumonisin B1-sensitive and acyl-CoAβdependent ceramide synthase reaction |
| GO:0046513 ceramide biosynthetic process | IDA PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | ACCEPT | Summary: IDA (Vallee & Riezman 2005) - purified Lac1 co-purifies with ceramide synthase activity. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0046513 ceramide biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR016439, Lag1/Lac1 family). Correct. Supporting Evidence: PMID:11694577 LAG1 and LAC1 are the first genes to be identified that are required for the fumonisin B1-sensitive and acyl-CoAβdependent ceramide synthase reaction |
| GO:0046513 ceramide biosynthetic process | IMP PMID:11694577 Lag1p and Lac1p are essential for the Acyl-CoA-dependent cer... | ACCEPT | Summary: IMP (Schorling et al. 2001) - lag1 lac1 cells are blocked in acyl-CoA-dependent ceramide synthesis. Supporting Evidence: PMID:11694577 lag1 Ξ lac1 Ξ cells have reduced sphingolipid levels due to a block of the fumonisin B1-sensitive and acyl-CoAβdependent ceramide synthase reaction |
| GO:0050291 sphingosine N-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000285423) for sphingosine N-acyltransferase (ceramide synthase) activity, seeded by CERS family members across eukaryotes including Lac1/Lag1. Correct. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0050291 sphingosine N-acyltransferase activity | IDA PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | ACCEPT | Summary: IDA (Vallee & Riezman 2005) - purified tagged Lac1 complex has acyl-CoA-dependent, FB1-sensitive ceramide synthase activity with the cellular chain-length specificity. Core activity. Supporting Evidence: PMID:15692566 In purified form, the acyl-CoA dependence, fatty acyl-CoA chain length specificity, and Fumonisin B1/Australifungin sensitivity of the ceramide synthase were the same as in cells |
| GO:0050291 sphingosine N-acyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO IEA (IPR016439). Correct. Supporting Evidence: file:yeast/LAC1/LAC1-uniprot.txt transfer of the acyl chain from acyl-CoA to a sphingoid base, with high |
| GO:0050291 sphingosine N-acyltransferase activity | IMP PMID:11387200 C26-CoA-dependent ceramide synthesis of Saccharomyces cerevi... | ACCEPT | Summary: IMP (Guillas et al. 2001) - lag1 lac1 microsomes lack C26-CoA:sphingoid base acyltransferase activity. Supporting Evidence: PMID:11387200 Here we show that microsomes or detergent extracts from lag1Ξ lac1Ξ double mutants lack an activity transferring C26 fatty acids from C26-coenzyme A onto dihydrosphingosine or phytosphingosine. |
| GO:0050291 sphingosine N-acyltransferase activity | IMP PMID:11694577 Lag1p and Lac1p are essential for the Acyl-CoA-dependent cer... | ACCEPT | Summary: IMP (Schorling et al. 2001) - lag1 lac1 cells blocked in acyl-CoA-dependent ceramide synthase reaction. Supporting Evidence: PMID:11694577 LAG1 and LAC1 are the first genes to be identified that are required for the fumonisin B1-sensitive and acyl-CoAβdependent ceramide synthase reaction |
| GO:0061576 acyl-CoA ceramide synthase complex | IDA PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | ACCEPT | Summary: IDA (Vallee & Riezman 2005) - Lac1 purified as a subunit of acyl-CoA ceramide synthase. Supporting Evidence: PMID:15692566 They copurified with ceramide synthase activity, giving unequivocal evidence that they are subunits of the enzyme. |
| GO:0061576 acyl-CoA ceramide synthase complex | IPI PMID:15692566 Lip1p: a novel subunit of acyl-CoA ceramide synthase. | ACCEPT | Summary: IPI (Vallee & Riezman 2005) - Lac1 co-purifies with Lip1 (and Lag1) in the ceramide synthase. Supporting Evidence: PMID:15692566 SDS-PAGE analysis of purified ceramide synthase revealed the presence of a novel subunit of the enzyme, Lip1p. |
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