IMD2 (PUR5; YHR216W) encodes one of three expressed inosine-5'-monophosphate dehydrogenases (IMPDH; EC 1.1.1.205) of S. cerevisiae (with IMD3 and IMD4; IMD1 is a poorly expressed subtelomeric paralog). IMPDH oxidises IMP to XMP with NAD+, the first committed and rate-limiting step of guanine nucleotide synthesis, followed by Gua1 (XMP -> GMP). IMD2 is the uniquely regulated paralog: its transcription is induced by guanine nucleotide depletion (e.g. by mycophenolic acid or 6-azauracil) through promoter elements that respond to nucleotide pools, and is coupled to growth rate, and its enzyme is intrinsically resistant to mycophenolic acid; loss of IMD2, but not of the other paralogs, causes drug sensitivity. IMPDH tetramers can contain more than one paralog. Imd2 is cytoplasmic; it has also been detected on transcribed chromatin and in mRNP complexes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: IEA from HAMAP MF_03156. IMP and NAD+ are nucleotide substrates; true but subsumed by IMP dehydrogenase activity. Reason: Substrate/cofactor binding implied by the catalytic MF. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0000785 chromatin | IDA PMID:20097157 IMP dehydrogenase is recruited to the transcription complex ... | KEEP AS NON CORE | Summary: IDA (Park & Ahn 2010): IMPDH (Imd2) was recruited to actively transcribed genes via Ser2-phosphorylated RNA Pol II CTD by ChIP. Abstract-only; accept as non-core, secondary to the metabolic role. Reason: Experimental ChIP-based association; moonlighting role with unclear function. Supporting Evidence: PMID:20097157 IMPDHs were recruited to elongating RNApII only when serine 2 of the CTD was phosphorylated by Ctk1 PMID:20097157 identified that Imd2 genetically interacts with Ctk1 |
| GO:0003682 chromatin binding | IDA PMID:20097157 IMP dehydrogenase is recruited to the transcription complex ... | KEEP AS NON CORE | Summary: IDA (Park & Ahn 2010): ChIP shows Imd2 association with transcribed chromatin dependent on Ctk1-mediated CTD Ser2 phosphorylation, i.e. probably via the elongation complex rather than direct chromatin binding. Non-core. Reason: ChIP-based association; binding is likely indirect via elongating Pol II. Supporting Evidence: PMID:20097157 IMPDHs were recruited to elongating RNApII only when serine 2 of the CTD was phosphorylated by Ctk1 |
| GO:0003729 mRNA binding | HDA PMID:23222640 Global analysis of yeast mRNPs. | KEEP AS NON CORE | Summary: HDA from global mRNP capture (Mitchell et al. 2013), which recovered all three IMPDHs among metabolic proteins bound to poly(A) RNA. IMPDH CBS domains bind nucleic acids in other species, but no specific mRNA-related role is established for IMD2. Reason: High-throughput mRNP capture; no defined RNA-related function. Supporting Evidence: PMID:23222640 Various metabolic proteins were observed (Imd2, Imd3, Imd4, Cys4, Cpr1) |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA from InterPro IPR001093 (IMPDH/GMPR). True but uninformative. Reason: Uninformative root MF. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PANTHER PTN000226903 (IMPDH). IMD2 is one of the three expressed yeast IMPDH paralogs; core MF. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0003938 IMP dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:11708 / EC 1.1.1.205, InterPro IPR005990 and HAMAP MF_03156. Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways), assigning IMD2 (with Imd3/Imd4) to IMP + NAD+ -> XMP + NADH (EC 1.1.1.205). Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0003938 IMP dehydrogenase activity | TAS PMID:11441018 Regulation of an IMP dehydrogenase gene and its overexpressi... | ACCEPT | Summary: TAS (Shaw et al. 2001): IMD1-4 encode IMPDH family members; IMPDH is rate-limiting for GTP synthesis. Accept; IMD2 carries the conserved catalytic residues (Cys335 active site). Supporting Evidence: PMID:11441018 IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the Huh et al. 2003 GFP screen: IMD2-GFP is cytoplasmic. Correct. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in cytoplasm) from PTN000226902. Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:23222640 Global analysis of yeast mRNPs. | ACCEPT | Summary: IDA from the global mRNP study (Mitchell et al. 2013), which identified the IMPDHs among novel mRNA-binding proteins and imaged mRNA-binding proteins in the cytoplasm; the specific IMD2 image is not in the cached text, so defer to the curator. Consistent with GFP and HAMAP data. Supporting Evidence: PMID:23222640 Various metabolic proteins were observed (Imd2, Imd3, Imd4, Cys4, Cpr1) file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from UniProt subcellular location SL-0086 / HAMAP. Correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: RCA (is_active_in cytosol) from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). IMPDH is a soluble cytoplasmic enzyme; cytosol is appropriate. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0006164 purine nucleotide biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR005990. Correct general BP. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0006164 purine nucleotide biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE2-PWY (superpathway of purine nucleotides de novo biosynthesis II). IMP -> XMP is the committed step of guanine nucleotide synthesis; correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0006164 purine nucleotide biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways DENOVOPURINE3-PWY (de novo biosynthesis of purine nucleotides). IMP -> XMP is the committed step of guanine nucleotide synthesis; correct. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0006177 GMP biosynthetic process | IEA GO_REF:0000104 | ACCEPT | Summary: IEA from HAMAP MF_03156. Correct; 'de novo GMP biosynthetic process' is more precise. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0006183 GTP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000226903. IMPDH is rate-limiting for guanine nucleotide (GTP) synthesis; correct, acting through GMP. Supporting Evidence: PMID:11441018 IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP |
| GO:0006183 GTP biosynthetic process | TAS PMID:11441018 Regulation of an IMP dehydrogenase gene and its overexpressi... | ACCEPT | Summary: TAS (Shaw et al. 2001): IMPDH is the rate-limiting enzyme for GTP synthesis. Correct. Supporting Evidence: PMID:11441018 IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP |
| GO:0009165 nucleotide biosynthetic process | RCA GO_REF:0000123 | TOO GENERAL | Summary: RCA from YeastPathways superpathway PRPP-PWY-1 (superpathway of histidine, purine, and pyrimidine biosynthesis). True but uninformative. Reason: True but very general parent from a superpathway. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: IEA from InterPro IPR015875 (IMPDH/GMPR conserved site). True but uninformative. Reason: Uninformative parent of the core MF. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+) |
| GO:0043101 purine-containing compound salvage | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: RCA from YeastPathways PWY3O-285 (superpathway of purine biosynthesis and salvage pathways). IMP produced by hypoxanthine salvage (Hpt1) or from adenine (Apt1/Amd1) reaches guanine nucleotides only via IMPDH, so IMPDH acts downstream of these salvage routes; guanine salvage by Hpt1 produces GMP directly. Non-core. Reason: IMPDH routes salvaged IMP to guanine nucleotides, but guanine salvage itself bypasses it. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides |
| GO:0046872 metal ion binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: IEA from HAMAP MF_03156: IMPDHs bind a monovalent K+ activator at the subunit interface. Correct but secondary to the catalytic MF. Reason: Cofactor binding; correct but secondary. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Name=K(+) |
| GO:0106387 'de novo' GMP biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-6125 (superpathway of guanosine nucleotides de novo biosynthesis II). IMP -> XMP is the first committed step of GMP synthesis via IMP; the most precise BP. Core BP. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides PMID:11441018 IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP |
| GO:0106387 'de novo' GMP biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-7221 (guanosine ribonucleotides de novo biosynthesis). IMP -> XMP is the first committed step of GMP synthesis via IMP; the most precise BP. Core BP. Supporting Evidence: file:yeast/IMD2/IMD2-uniprot.txt Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides PMID:11441018 IMP dehydrogenase is a rate-limiting enzyme involved in the synthesis of GTP |
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Download this section (compressed HTML)Q: Does IMPDH recruitment to elongating RNA Pol II reflect a catalytic role (local GTP supply) or a non-catalytic nucleic-acid-binding role?
Q: What fraction of total cellular IMPDH activity is contributed by Imd2 versus Imd3/Imd4 under normal growth?
Experiment: Express catalytically inactive (Cys335Ala) Imd2 and test whether it restores Ctk1 promoter association and chromatin recruitment in imd2 cells.
Inosine monophosphate dehydrogenase; catalyzes the rate-limiting step in GTP biosynthesis, expression is induced by mycophenolic acid resulting in resistance to the drug, expression is repressed by nutrient limitation; IMD2 has a paralog, YAR073W/YAR075W, that arose from a segmental duplication
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