TSC13 (YDL015C) encodes the very-long-chain enoyl-CoA reductase (trans-2-enoyl-CoA reductase, TECR orthologue) of the endoplasmic reticulum fatty acid elongation system, a polytopic ER membrane protein of the steroid 5-alpha-reductase family. It catalyses the NADPH-dependent reduction of trans-2,3-enoyl-CoA, the fourth and final step of each elongation cycle, regenerating a saturated acyl-CoA two carbons longer that can re-enter the cycle; together with the condensing enzymes Elo2/Elo3, the 3-ketoreductase Ifa38 and the dehydratase Phs1 it produces the C20-C26 very long-chain fatty acids that form the acyl chains of yeast ceramide and sphingolipids. TSC13 is essential and has no paralogue; tsc13 hypomorphs accumulate trans-2-enoyl- and 3-hydroxy-acyl-CoA intermediates, long-chain bases and ceramides with shortened fatty acids. Tsc13 co-immunoprecipitates with Elo2 and Elo3 and, besides the general ER, is enriched at nucleus-vacuole junctions through binding Nvj1, where VLCFA supply supports normal piecemeal microautophagy of the nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000038 very long-chain fatty acid metabolic process | IMP PMID:11113186 Tsc13p is required for fatty acid elongation and localizes t... | ACCEPT | Summary: Kohlwein et al. 2001: tsc13 mutants are defective in VLCFA synthesis (accumulate long-chain bases and <C26 ceramides; synthetic lethal with reduced malonyl-CoA). Correct; VLCFA biosynthesis is the more precise child term. Supporting Evidence: PMID:11113186 The tsc13 mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons PMID:11113186 Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis |
| GO:0005515 protein binding | IPI PMID:20937905 ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingol... | REMOVE | Summary: IPI with human ELOVL1 (UniProtKB:Q9BW60) from Ohno et al. 2010, a study of mammalian ELOVL substrate specificity. The interaction is consistent with conserved assembly of the condensing enzyme with the enoyl reductase, but 'protein binding' conveys no function; the yeast-relevant partners are Elo2 and Elo3. Reason: Uninformative generic binding term with a cross-species partner; removal does not mean the interaction is false. The meaningful biology (association with the condensing enzymes in the elongase) is captured by the catalytic and process annotations. Supporting Evidence: PMID:20937905 Elongases catalyze the first of four steps in the VLCFA elongation cycle PMID:11113186 Tsc13p coimmunoprecipitates with Elo2p and Elo3p, suggesting that the elongating proteins are organized in a complex |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | KEEP AS NON CORE | Summary: Sickmann et al. 2003 mitochondrial proteome (MS) detected Tsc13. Reason: Tsc13 is a polytopic ER membrane protein enriched at nucleus-vacuole junctions; detection in purified mitochondria by mass spectrometry most likely reflects ER/mitochondria contact-site co-purification. No mitochondrial function is described. Kept as non-core rather than removed because these are experimental HDA calls. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: Reinders et al. 2006 PROMITO mitochondrial proteome detected Tsc13. Reason: Tsc13 is a polytopic ER membrane protein enriched at nucleus-vacuole junctions; detection in purified mitochondria by mass spectrometry most likely reflects ER/mitochondria contact-site co-purification. No mitochondrial function is described. Kept as non-core rather than removed because these are experimental HDA calls. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS |
| GO:0005783 endoplasmic reticulum | HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein... | ACCEPT | Summary: Tkach et al. 2012 high-throughput GFP-collection imaging scored Tsc13-GFP at the ER. Supporting Evidence: PMID:22842922 high-throughput microscopic screening of the yeast GFP fusion collection file:yeast/TSC13/TSC13-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: Yofe et al. 2016 SWAT N-terminal GFP library of endomembrane proteins localised Tsc13 to the ER. Supporting Evidence: PMID:26928762 we constructed and investigated a library of βΌ1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the TECR/steroid 5-alpha reductase-family node PTN000059180; ER residence shared by characterised trans-2-enoyl-CoA reductases. Supporting Evidence: PMID:11113186 Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions file:yeast/TSC13/TSC13-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:15958487 Targeting of Tsc13p to nucleus-vacuole junctions: a role for... | ACCEPT | Summary: Kvam et al. 2005: Tsc13 is a polytopic ER membrane protein sequestered at nucleus-vacuole junctions by Nvj1. Supporting Evidence: PMID:15958487 Tsc13p is a polytopic endoplasmic reticulum (ER) membrane protein that accumulates at nucleus-vacuole (NV) junctions file:yeast/TSC13/TSC13-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:11113186 Tsc13p is required for fatty acid elongation and localizes t... | ACCEPT | Summary: Kohlwein et al. 2001: functional chromosomal Tsc13-GFP gives perinuclear and peripheral ER staining, enriched at nucleus-vacuole junctions; integral membrane behaviour by detergent extraction. Supporting Evidence: PMID:11113186 Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location keyword mapping (SL-0097) from the experimental ER membrane statement. Supporting Evidence: file:yeast/TSC13/TSC13-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways PWY-5080-1 GO-CAM conversion default 'is_active_in cytosol'. Tsc13 is a polytopic integral ER membrane protein. Reason: Computational compartment default contradicted by experimental ER membrane localisation. Supporting Evidence: PMID:15958487 Tsc13p is a polytopic endoplasmic reticulum (ER) membrane protein that accumulates at nucleus-vacuole (NV) junctions file:yeast/TSC13/TSC13-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from IPR001104 (3-oxo-5-alpha-steroid 4-dehydrogenase C-terminal domain) to lipid metabolic process; true but uninformative. Proposed replacements: very long-chain fatty acid biosynthetic process Supporting Evidence: file:yeast/TSC13/TSC13-uniprot.txt SIMILARITY: Belongs to the steroid 5-alpha reductase family. PMID:11113186 These results indicate that Tsc13p catalyzes a step in elongation subsequent to the condensation step. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000041 | MODIFY | Summary: UniPathway UPA00094 (fatty acid biosynthesis) mapping; correct but Tsc13 acts specifically in VLCFA elongation. Proposed replacements: very long-chain fatty acid biosynthetic process Supporting Evidence: PMID:11113186 These results indicate that Tsc13p catalyzes a step in elongation subsequent to the condensation step. PMID:11113186 Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis |
| GO:0006665 sphingolipid metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA for sphingolipid metabolic process. Tsc13 provides the VLCFA-CoA for C26 ceramide; tsc13 mutants accumulate long-chain bases and short-chain ceramides. Precursor-supply role, not a sphingolipid-metabolising step. Supporting Evidence: PMID:11113186 The tsc13 mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons |
| GO:0016491 oxidoreductase activity | IMP PMID:11113186 Tsc13p is required for fatty acid elongation and localizes t... | MODIFY | Summary: Kohlwein et al. 2001: tsc13 microsomes accumulate trans-2-enoyl- and 3-hydroxy-acyl-CoA intermediates, implicating the enoyl reduction step. 'Oxidoreductase activity' is far too general. Proposed replacements: very-long-chain enoyl-CoA reductase activity Supporting Evidence: PMID:11113186 These results indicate that Tsc13p catalyzes a step in elongation subsequent to the condensation step. PMID:11113186 This is consistent with the defect in Tsc13p causing reduced activity of the trans -2,3-enoyl-CoA reductase leading to accumulation of the trans -2,3-stearoyl-CoA. |
| GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping (IPR001104) to oxidoreductase acting on CH-CH donors; correct class but generic. Proposed replacements: very-long-chain enoyl-CoA reductase activity Supporting Evidence: file:yeast/TSC13/TSC13-uniprot.txt SIMILARITY: Belongs to the steroid 5-alpha reductase family. file:yeast/TSC13/TSC13-uniprot.txt Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a |
| GO:0019166 trans-2-enoyl-CoA reductase (NADPH) activity | IEA GO_REF:0000116 | MODIFY | Summary: IEA from Rhea VLC enoyl-CoA reductions mapped to trans-2-enoyl-CoA reductase (NADPH) activity (EC 1.3.1.38). The chemistry is right but GO:0102758 (EC 1.3.1.93) is the precise VLC term and is not a descendant of this one. Proposed replacements: very-long-chain enoyl-CoA reductase activity Supporting Evidence: file:yeast/TSC13/TSC13-uniprot.txt Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a |
| GO:0042761 very long-chain fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000059180) for VLCFA biosynthesis; core process for Tsc13. Supporting Evidence: PMID:11113186 Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis PMID:11113186 These results indicate that Tsc13p catalyzes a step in elongation subsequent to the condensation step. |
| GO:0042761 very long-chain fatty acid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5080-1 assignment of the enoyl-CoA reduction step to Tsc13; correct. Supporting Evidence: PMID:11113186 This is consistent with the defect in Tsc13p causing reduced activity of the trans -2,3-enoyl-CoA reductase leading to accumulation of the trans -2,3-stearoyl-CoA. PMID:17719544 Proteoliposomes reconstituted here from purified membrane components-an elongase protein (Elop), a novel dehydratase, and two reductases-catalyzed repeated rounds of two-carbon addition |
| GO:0102758 very-long-chain enoyl-CoA reductase activity | EXP PMID:11113186 Tsc13p is required for fatty acid elongation and localizes t... | ACCEPT | Summary: Kohlwein et al. 2001 showed tsc13 microsomes are defective after condensation and accumulate the trans-2-enoyl intermediate; Tsc13 is the sole enoyl reductase of the cycle in yeast. Later reconstitution (Denic and Weissman 2007) confirmed two reductases complete the cycle. Supporting Evidence: PMID:11113186 This is consistent with the defect in Tsc13p causing reduced activity of the trans -2,3-enoyl-CoA reductase leading to accumulation of the trans -2,3-stearoyl-CoA. PMID:11113186 Based on its homology to steroid-5-Ξ±-reductase, Tsc13p may directly catalyze the reduction of the enoyl intermediate in each cycle of fatty acid elongation. PMID:17719544 Proteoliposomes reconstituted here from purified membrane components-an elongase protein (Elop), a novel dehydratase, and two reductases-catalyzed repeated rounds of two-carbon addition |
| GO:0102758 very-long-chain enoyl-CoA reductase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000059180) for VLC enoyl-CoA reductase activity; the defining activity of TECR/Tsc13 orthologues, with target-specific experimental support. Supporting Evidence: PMID:11113186 This is consistent with the defect in Tsc13p causing reduced activity of the trans -2,3-enoyl-CoA reductase leading to accumulation of the trans -2,3-stearoyl-CoA. file:yeast/TSC13/TSC13-uniprot.txt Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a |
| GO:0102758 very-long-chain enoyl-CoA reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (RHEA:14473, EC 1.3.1.93) matching the UniProt-curated catalytic activity. Supporting Evidence: file:yeast/TSC13/TSC13-uniprot.txt Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a |
| GO:0102758 very-long-chain enoyl-CoA reductase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5080-1 (EC 1.3.1.93) assignment of the trans-2-enoyl-CoA reduction to Tsc13; correct. Supporting Evidence: PMID:11113186 This is consistent with the defect in Tsc13p causing reduced activity of the trans -2,3-enoyl-CoA reductase leading to accumulation of the trans -2,3-stearoyl-CoA. file:yeast/TSC13/TSC13-uniprot.txt Reaction=a very-long-chain 2,3-saturated fatty acyl-CoA + NADP(+) = a |
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Download this section (compressed HTML)Q: Why is Tsc13, unlike the other elongation enzymes, concentrated at nucleus-vacuole junctions, and does local VLCFA production there contribute directly to piecemeal microautophagy membrane formation?
Q: Does Tsc13 also act as the trans-2-enoyl-CoA reductase in sphingosine-1-phosphate/long-chain base degradation in yeast, as TECR does in mammals?
Experiment: Compare PMN bleb/vesicle diameter and VLCFA profiles in nvj1 cells expressing Tsc13 versus a Tsc13 variant fused to an Nvj1-binding domain that restores junction targeting.
Hypothesis: Nvj1-mediated sequestration of Tsc13 at nucleus-vacuole junctions is required for normal PMN vesicle size independently of bulk VLCFA levels.
Enoyl reductase; catalyzes last step in each cycle of very long chain fatty acid elongation; localizes to ER, highly enriched in a structure marking nuclear-vacuolar junctions; coimmunoprecipitates with elongases Elo2p and Elo3p; protein increases in abundance and relative distribution to ER foci increases upon DNA replication stress; human homolog TECR implicated in nonsyndromic mental retardation, can complement yeast mutant
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