Des-methyl-DIF-1 methyltransferase A (DmtA) is a soluble, S-adenosyl-L-methionine-dependent O-methyltransferase of the cation-independent COMT subfamily that catalyzes the final step of DIF-1 (differentiation-inducing factor 1) biosynthesis in Dictyostelium discoideum. DIF-1 is a chlorinated alkyl phenone polyketide morphogen. Its biosynthesis begins with assembly of the C12 polyketide (2,4,6-trihydroxyphenyl)-1-hexan-1-one (THPH) by the polyketide synthase StlB, which is dichlorinated by the flavin-dependent halogenase ChlA to give des-methyl-DIF-1 (dichloro-THPH); DmtA then O-methylates des-methyl-DIF-1 to yield mature DIF-1. DIF-1 is a diffusible signal that induces prestalk-O (pstO) cell differentiation and specifies the anterior-like cells that form the basal disc and much of the lower cup of the fruiting body. dmtA is maximally expressed in prespore cells around the first-finger/slug stage, is induced by cyclic-AMP, and is repressed by DIF-1. Loss of DmtA blocks DIF-1 production and causes accumulation of the biosynthetic intermediate des-methyl-DIF-1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008171 O-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of O-methyltransferase activity is correct. DmtA is a functionally characterized O-methyltransferase that transfers a methyl group to a hydroxyl of its dichloro-THPH substrate. Reason: The general MF term is accurate and consistent with the experimentally characterized activity, though the specific reaction is better captured by GO:0106268. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0008757 S-adenosylmethionine-dependent methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: DmtA uses S-adenosyl-L-methionine as the methyl donor, so this SAM-dependent methyltransferase grouping term is correct. Reason: Directly supported by enzymology showing the methyltransferase uses SAM as co-substrate; consistent with the class I-like SAM-binding methyltransferase superfamily assignment. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0032259 methylation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: This is a very general biological-process grouping term. DmtA does carry out methylation, but the specific and informative process is DIF-1 biosynthesis via O-methylation of des-methyl-DIF-1. Reason: The term is correct but too general to represent the core function; the specific DIF-1 biosynthetic process (GO:0031148) is the informative annotation. Supporting Evidence: PMID:9446571 Conversion requires both chlorination and methylation of THPH, and enzymatic activities able to do this exist in cell lysates |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct but general parent term for methyltransferase activity, subsumed by the more specific O-methyltransferase and dichloro-THPH methyltransferase annotations. Reason: Accurate grouping term consistent with the experimentally established methyltransferase activity; retained as an accurate but non-specific parent. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0008171 O-methyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO inference of O-methyltransferase activity from the COMT-like domain signature. This is correct for DmtA. Reason: The domain-based inference agrees with the experimentally determined O-methyltransferase activity of DmtA. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: This InterPro2GO annotation derives from the COMT dimerisation domain (PF08100) present in the protein. Many cation-independent COMT-family O-methyltransferases function as homodimers, so dimerization is plausible on structural grounds, but there is no direct experimental evidence that DmtA dimerizes and this is not an informative functional annotation. Reason: The dimerization inference is a domain-based structural prediction, not experimentally verified for DmtA, and does not describe the gene's catalytic or biological function. Retained as non-core rather than removed because the dimerisation domain is genuinely present and functionally plausible for the COMT family. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0106268 3,5-dichloro-THPH methyl transferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: This Rhea-based term captures the precise reaction catalyzed by DmtA - O-methylation of (3,5-dichloro-2,4,6-trihydroxyphenyl)hexan-1-one (des-methyl-DIF-1) using SAM to yield DIF-1. This is the core molecular function. Reason: This is the specific, biochemically demonstrated catalytic activity of DmtA and represents its core molecular function. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0106268 3,5-dichloro-THPH methyl transferase activity | EXP PMID:9446571 The biosynthesis of differentiation-inducing factor, a chlor... | ACCEPT | Summary: Experimental evidence from enzymological characterization of the DIF-1 methyltransferase activity in Dictyostelium lysates, showing SAM-dependent O-methylation of dichloro-THPH with strong substrate preference. This is the core catalytic function of DmtA. Reason: Direct experimental characterization of the methyltransferase catalyzing the final step of DIF-1 biosynthesis; the defining core function of the gene. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues PMID:9446571 Conversion requires both chlorination and methylation of THPH, and enzymatic activities able to do this exist in cell lysates |
| GO:0010623 programmed cell death involved in cell development | IMP PMID:28055008 Early nucleolar disorganization in Dictyostelium cell death. | KEEP AS NON CORE | Summary: In this study the DmtA-null (DIF-1-deficient) strain was used as a tool to test whether endogenous DIF-1 is required for developmental cell death. Vacuolar developmental cell death and its early hallmarks were induced in DmtA-null cells by an exogenous second signal (DIF-1 or c-di-GMP), and initial priming did not require endogenous DIF-1. Thus DmtA itself is not directly required for the death program; the connection to cell death is indirect, via the DIF-1 morphogen it produces. Reason: The annotation reflects a downstream developmental role of the DmtA-produced DIF-1 signal rather than a core molecular or biosynthetic function of the protein. DmtA-null cells still undergo developmental cell death when supplied exogenous DIF-1, so this is a non-core developmental context. Supporting Evidence: PMID:28055008 DH1.DmtA- mutant cells (Figure 2) unable to synthesize DIF-1 |
| GO:0031149 sorocarp stalk cell differentiation | IMP PMID:18402932 DIF-1 induces the basal disc of the Dictyostelium fruiting b... | KEEP AS NON CORE | Summary: The dmtA-null mutant, blocked in the last step of DIF-1 synthesis, shows delayed tip formation and fewer prestalk-O cells, and (like other DIF-1 pathway mutants) a defective basal disc, consistent with a role of DmtA-produced DIF-1 in prestalk/stalk cell differentiation. This is a downstream developmental consequence of DIF-1 production. Reason: Correct developmental phenotype attributable to loss of the DIF-1 signal made by DmtA, but this is a downstream morphogenetic role rather than the core catalytic function of the gene product. Supporting Evidence: PMID:18402932 The dmtA(-) methyltransferase mutant, blocked in the last step of DIF-1 synthesis, resembles the stlB(-) mutant but has delayed tip formation and fewer prestalk-O cells |
| GO:0031288 sorocarp morphogenesis | IMP PMID:18402932 DIF-1 induces the basal disc of the Dictyostelium fruiting b... | KEEP AS NON CORE | Summary: Loss of DmtA (and hence DIF-1) produces fruiting-body morphogenesis defects shared with other DIF-1 signaling mutants, including near-absence of the basal disc. This is a downstream developmental role of the DIF-1 signal. Reason: The morphogenesis phenotype is a valid developmental consequence of loss of DmtA-produced DIF-1, but is downstream of and non-core relative to the enzyme's biosynthetic function. Supporting Evidence: PMID:18402932 This is a common feature of DIF-1 signaling mutants also found in dmtA, dimA, and mybE strains PMID:18402932 DIF-1 is required for slug migration and specifies the anterior-like cells forming the basal disc |
| GO:0030435 sporulation resulting in formation of a cellular spore | IMP PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | KEEP AS NON CORE | Summary: This IMP annotation derives from characterization of the DIF-1 biosynthesis mutant during multicellular development. The cached record for this reference is abstract-only and the abstract focuses on prestalk (pstO) cell induction rather than sporulation, so the specific sporulation phenotype cannot be independently verified here; the curator annotation is from the full text. This is at most a downstream developmental role of the DIF-1 pathway, not a core function. Reason: Retained as a non-core developmental annotation, deferring to the curator's reading of the full text; DmtA's core function is DIF-1 biosynthesis, and any effect on spore formation is downstream and indirect. |
| GO:0031154 culmination involved in sorocarp development | IMP PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | KEEP AS NON CORE | Summary: DIF-1 pathway loss affects late multicellular development including culmination; the related study of the DIF-1 synthesis (PKS) mutant notes that the basal-disc defect may cause culmination to initiate along the substratum. This is a downstream developmental role of the DIF-1 signal produced by DmtA rather than a core molecular function. Reason: A valid downstream developmental context attributable to loss of the DIF-1 morphogen, but non-core relative to the enzyme's biosynthetic activity. Supporting Evidence: PMID:18402932 which perhaps in consequence initiates culmination along the substratum |
| GO:0031148 DIF-1 biosynthetic process | IDA PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | ACCEPT | Summary: DmtA catalyzes the final O-methylation step of DIF-1 biosynthesis, so it is directly involved in the DIF-1 biosynthetic process. Construction of a mutant blocked in DIF-1 biosynthesis established this pathway role. This is a core biological-process annotation. Reason: DmtA performs the terminal methylation reaction of the DIF-1 biosynthetic pathway; this is a core annotation directly supported by enzymology and mutant analysis. Supporting Evidence: PMID:11163223 a mutant blocked in the biosynthesis of DIF-1, a chlorinated signal molecule proposed to induce differentiation of both major prestalk cell types PMID:18402932 and then methylated to produce DIF-1, with methylation catalyzed by the DmtA methyl transferase |
| GO:0045595 regulation of cell differentiation | IMP PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | KEEP AS NON CORE | Summary: By producing the DIF-1 morphogen, DmtA acts upstream of prestalk/stalk cell differentiation. The DIF-1 biosynthesis mutant fails to make pstO cells, which are restored by exogenous DIF-1. This is a general downstream developmental-regulatory role rather than a core function. Reason: The gene influences cell differentiation only indirectly, through the DIF-1 signal it synthesizes; the term is general and downstream, so it is retained as non-core. Supporting Evidence: PMID:11163223 Normal pstO cell differentiation and their patterning in the slug are restored by development on a uniform concentration of DIF-1 |
| GO:0008171 O-methyltransferase activity | IDA PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | ACCEPT | Summary: Direct-assay annotation of O-methyltransferase activity for DmtA, consistent with the enzymological characterization of the DIF-1 methyltransferase. Correct core-level molecular function (specific reaction captured by GO:0106268). Reason: Agrees with the experimentally established O-methyltransferase activity of DmtA on the des-methyl-DIF-1 substrate. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
| GO:0008757 S-adenosylmethionine-dependent methyltransferase activity | IDA PMID:11163223 The role of DIF-1 signaling in Dictyostelium development. | ACCEPT | Summary: Direct-assay annotation that DmtA is a SAM-dependent methyltransferase, consistent with the demonstration that the DIF-1 methyltransferase uses S-adenosyl-L-methionine as co-substrate. Reason: Correct molecular function supported by enzymology showing SAM dependence of the methyltransferase. Supporting Evidence: PMID:9446571 The methyltransferase is soluble, uses S-adenosyl-L-methionine as a co-substrate, has a Km for dichloro-THPH of about 1.1 microM, and strongly prefers this substrate to close analogues |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)