HTD2 (YHR067W; also RMD12) encodes the mitochondrial 3-hydroxyacyl-thioester dehydratase 2 of type II fatty acid synthesis (FAS II). Htd2 is a hot-dog fold enzyme of the thioesterase/thioester dehydratase-isomerase superfamily that dehydrates (3R)-3-hydroxyacyl-ACP to trans-2-enoyl-ACP, the third step of each FAS II elongation cycle, between the 3-oxoacyl-ACP reductase Oar1 and the enoyl-thioester reductase Etr1. As for other FAS II components, loss of HTD2 makes cells respiratory deficient, lacking cytochromes and with abnormal mitochondrial morphology, consistent with the requirement of FAS II-derived octanoyl-ACP for lipoic acid synthesis; overexpression enlarges mitochondria. htd2 mutants were isolated as cells that could not lose a plasmid encoding a mitochondrially targeted bacterial FAS II analogue.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 GFP survey: mitochondrial. Correct, consistent with the experimental localisation. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Reinders et al. 2006 mitochondrial proteome detects Htd2. Correct. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT is_active_in mitochondrion on the fungal HTD2 node (PTN001999711) grounded on Htd2 itself. Correct. |
| GO:0005739 mitochondrion | IDA PMID:15387819 Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essen... | ACCEPT | Summary: Kastaniotis et al. 2004 localised Htd2 to mitochondria (UniProt cites this paper for the location). Core location; matrix would be more precise but is not directly shown. Supporting Evidence: file:yeast/HTD2/HTD2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095, |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro IPR026223 (HTD2 family) / SubCell mapping to mitochondrion. Correct. |
| GO:0006631 fatty acid metabolic process | ISS PMID:15387819 Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essen... | TOO GENERAL | Summary: ISS from FOX2 (SGD:S000001717), the peroxisomal multifunctional enzyme type 2 whose hydratase 2 domain shares the (R)-specific hot-dog dehydratase chemistry. The broad 'fatty acid metabolic process' is correct but Htd2 acts in mitochondrial fatty acid synthesis, not beta-oxidation; the specific biosynthetic term is preferable. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from IPR026223 (HTD2 family) to fatty acid biosynthetic process. Correct: Htd2 is the FAS II dehydratase. Core BP. Supporting Evidence: PMID:15387819 We describe here the identification of the 3-hydroxyacyl-ACP dehydratase involved in mitochondrial fatty acid synthesis. |
| GO:0019171 (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN001999710 seeded by yeast Htd2 itself (the target appearing in its own with/from reflects its experimental grounding). Sound. |
| GO:0019171 (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity | IDA PMID:15387819 Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essen... | ACCEPT | Summary: Hydratase 2 activity increased in mitochondrial extracts of HTD2-overexpressing cells, and the null mutant was isolated as requiring a mitochondrially targeted bacterial FAS II analogue. The in vitro assay used CoA thioesters (hydratase 2), the reverse direction of the ACP dehydratase reaction; the authors conclude Htd2 is the mitochondrial FAS 3-hydroxyacyl-ACP dehydratase. Accept as core MF. Supporting Evidence: PMID:15387819 Hydratase 2 activity in mitochondrial extracts from cells overexpressing YHR067w was increased. PMID:15387819 We conclude that YHR067w encodes a novel mitochondrial 3-hydroxyacyl-thioester dehydratase 2 and suggest renaming it HTD2. |
| GO:0019171 (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from IPR026223 (HTD2 family). Correct, consistent with the IDA. |
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Download this section (compressed HTML)Q: Does Htd2 act on ACP thioesters of all chain lengths produced by FAS II (C4-C16), and does it form a complex with other FAS II enzymes?
Q: Why is human HTD2 placed in a different PANTHER family (PTHR43437) from fungal Htd2, and are the mammalian and fungal enzymes convergent?
Experiment: Assay purified Htd2 with (3R)-3-hydroxyacyl-ACP substrates of different chain lengths, using holo-Acp1 acylated in vitro, to determine kinetic preference in the ACP-dependent direction.
Type: biochemistry
Mitochondrial 3-hydroxyacyl-thioester dehydratase; involved in fatty acid biosynthesis, required for respiratory growth and for normal mitochondrial morphology
UniProt P38790; module type_ii_fatty_acid_synthesis (dehydratase annoton, GO:0019171).
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