NTH2 (YBR001C) encodes a neutral (cytosolic-type) alpha,alpha-trehalase of glycoside hydrolase family 37, a paralog of the main neutral trehalase NTH1 that arose from the whole-genome duplication. Nth2 hydrolyses the disaccharide trehalose to two glucose molecules and contributes, with Nth1, to mobilisation of intracellular trehalose; its contribution is minor compared with Nth1. The protein retains the GH37 catalytic residues and the N-terminal calcium-binding region characteristic of fungal neutral trehalases. Trehalose breakdown by the neutral trehalases releases glucose from the stress-protective and reserve trehalose pool, whereas extracellular trehalose is hydrolysed by the acid trehalase Ath1. nth2 deletion mutants accumulate more intracellular trehalose than wild type, but in most strain backgrounds they survive acute heat stress as well as wild type; mild thermosensitivity is seen mainly when NTH1 is also lost.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004555 alpha,alpha-trehalase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT node PTN004635776 seeded by GH37 trehalases from E. coli (TreF/TreA), Drosophila, Arabidopsis, human, Candida, S. pombe ntp1 and yeast NTH1/ATH1. Nth2 retains the GH37 catalytic residues and has been shown to be a functional trehalase, so inheritance is sound. Supporting Evidence: PMID:18065618 NTH2, a paralog of NTH1, encodes a functional trehalase that is implicated in trehalose mobilization |
| GO:0004555 alpha,alpha-trehalase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro (IPR001661 GH37, IPR011120, IPR018232) plus RHEA:32675/EC 3.2.1.28 mapping. Correct for Nth2, whose trehalase function is experimentally supported. |
| GO:0004555 alpha,alpha-trehalase activity | IMP PMID:18065618 New insights into trehalose metabolism by Saccharomyces cere... | ACCEPT | Summary: Jules et al. 2008 showed that NTH2 encodes a functional trehalase involved in trehalose mobilisation (abstract-only cache; the curator read the full text). Core MF. Supporting Evidence: PMID:18065618 NTH2, a paralog of NTH1, encodes a functional trehalase that is implicated in trehalose mobilization |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO from IPR011120 (neutral trehalase Ca2+-binding domain). Fungal neutral trehalases such as Nth1 bind calcium through this N-terminal region; Nth2 shares the domain. Plausible cofactor binding, not shown directly for Nth2; non-core. |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 genome-wide GFP localization. Cytoplasmic localisation is consistent with Nth2 being a neutral (cytosolic) trehalase acting on intracellular trehalose. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from IPR011120 mapping the neutral trehalase Ca-binding domain to cytoplasm. Consistent with the HDA and the cytosolic function of neutral trehalases. |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | UNDECIDED | Summary: Huh et al. 2003 GFP survey reported a mitochondrial signal for Nth2 (abstract-only cache; the per-protein call cannot be checked here). No mitochondrial trehalose metabolism or functional role of Nth2 in mitochondria is known, and its paralog Nth1 acts in the cytosol. Cannot be adjudicated from the available evidence. |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from six-hairpin glycosidase superfamily domains (IPR008928, IPR012341) to the generic carbohydrate metabolic process. True but uninformative; trehalose catabolic process is the precise term. Reason: True but uninformative: the more specific GO:0005993 trehalose catabolic process is accepted in this review and entails it. TOO_GENERAL (judging the term), matching the same InterPro2GO row in the other trehalase/xylulose reviews of this PR. |
| GO:0005991 trehalose metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from GH37 trehalase entries to trehalose metabolic process. Correct parent of the more specific trehalose catabolic process. |
| GO:0005993 trehalose catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inheritance of trehalose catabolic process across GH37 trehalases. Sound for Nth2, which contributes to trehalose mobilisation. |
| GO:0005993 trehalose catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA00027072/IPR011120 mapping to trehalose catabolism. Correct for this neutral trehalase. |
| GO:0005993 trehalose catabolic process | IMP PMID:18065618 New insights into trehalose metabolism by Saccharomyces cere... | ACCEPT | Summary: Jules et al. 2008: Nth2 is implicated in trehalose mobilisation. Core BP; Nth1 is the dominant neutral trehalase and Nth2 a minor contributor. Supporting Evidence: PMID:18065618 NTH2, a paralog of NTH1, encodes a functional trehalase that is implicated in trehalose mobilization |
Loading supporting content…
Download this section (compressed HTML)Q: Is Nth2 regulated by PKA phosphorylation and 14-3-3 (Bmh1/2) binding as Nth1 is, and does it require calcium for activity?
Q: Under which conditions (heat-shock recovery, stationary phase, specific carbon sources) does Nth2 make a measurable contribution relative to Nth1?
Q: Is the reported mitochondrial GFP signal for Nth2 reproducible, and if so does it have any functional significance?
Experiment: Purify recombinant Nth2 and measure trehalase kinetics, Ca2+ dependence and PKA/Bmh-dependent activation in parallel with Nth1.
Type: biochemistry
Putative neutral trehalase, required for thermotolerance; may mediate resistance to other cellular stresses; NTH2 has a paralog, NTH1, that arose from the whole genome duplication
UniProt P35172; module trehalose_metabolism (cytosolic GH37 neutral trehalase annoton, GO:0004555).
Loading supporting content…
Download this section (compressed HTML)