IDI1 (isopentenyl-diphosphate delta-isomerase 1) is a small (227 aa) metalloenzyme of the type-1 IPP isomerase family (Nudix hydrolase fold) that catalyzes the reversible 1,3-allylic rearrangement interconverting the two five-carbon isoprene units of the mevalonate/isoprenoid pathway: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) (EC 5.3.3.2). By generating DMAPP, it provides the allylic primer that farnesyl diphosphate synthase and other prenyltransferases use to initiate and elongate prenyl chains, and it balances the cellular IPP/DMAPP pools that feed sterol (cholesterol), dolichol, ubiquinone, and protein-prenylation branches of isoprenoid metabolism. Catalysis requires a divalent metal cofactor (Mg2+, with Mn2+ also bound); the enzyme is a monomer with active-site residues His86 and Glu148. Human IDI1 is broadly (housekeeping) expressed and localizes to both the cytosol and the peroxisome, carrying a C-terminal PTS1-type microbody targeting signal. A paralogous isozyme, IDI2, is expressed only in skeletal muscle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment that IDI1 is active in the peroxisome. This is concordant with direct experimental localization of human IDI1 to the peroxisome (PMID:17180682, PMID:17202134) and the C-terminal PTS1-type targeting signal, so it is retained as a genuine location. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0004452 isopentenyl-diphosphate delta-isomerase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the family's defining molecular function. This is the correct core catalytic activity of IDI1, independently established experimentally (PMID:8806705). Retained as core. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt Reaction=isopentenyl diphosphate = dimethylallyl diphosphate; |
| GO:0009240 isopentenyl diphosphate biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment for the IPP isomerase family. IDI1 interconverts IPP and DMAPP rather than synthesizing IPP de novo, so this process term is somewhat imprecise for the reaction direction, but the isomerase does contribute to maintaining the IPP pool and this is the standard PAN-GO family term. Kept as a valid, if non-core, process; the more precise process is DMAPP biosynthesis (GO:0050992). Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt Reaction=isopentenyl diphosphate = dimethylallyl diphosphate; |
| GO:0004452 isopentenyl-diphosphate delta-isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (InterPro IPR011876 / RHEA:23284 / EC:5.3.3.2) of the core molecular function. Redundant with the experimental IDA and phylogenetic IBA annotations to the same term, and correct; accepted as representing the core function. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt EC=5.3.3.2 {ECO:0000269|PubMed:8806705} |
| GO:0005777 peroxisome | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic location assignment (ARBA / UniProtKB-SubCell SL-0204). Consistent with the direct experimental peroxisomal localization (PMID:17180682, PMID:17202134) and the PTS1-type microbody targeting signal; accepted as a genuine location. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt MOTIF 225..227 |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the overarching isoprenoid biosynthetic process. IDI1 provides the DMAPP allylic primer required for prenyl-chain elongation, so this is a correct core process for the gene; accepted. Supporting Evidence: PMID:8806705 Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes an essential activation step in the isoprenoid biosynthetic pathway. |
| GO:0016860 intramolecular oxidoreductase activity | IEA GO_REF:0000117 | MODIFY | Summary: Electronic (ARBA) assignment to a general isomerase-branch parent term. Verified via OLS that GO:0004452 is a descendant of GO:0016860 (GO:0004452 -> GO:0016863 -> GO:0016860 -> GO:0016853 isomerase activity), so this is not wrong, just less specific than the established activity. Replace with the specific term. Reason: Correct but overly general; the specific, experimentally established activity is isopentenyl-diphosphate delta-isomerase activity (GO:0004452). Proposed replacements: isopentenyl-diphosphate delta-isomerase activity |
| GO:0035634 response to stilbenoid | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-transferred (Ensembl Compara) annotation from mouse Idi1 (UniProtKB:P58044), reflecting transcriptional responsiveness of Idi1 to stilbenoid compounds (e.g. resveratrol) that modulate the cholesterol/isoprenoid pathway. This is a peripheral stimulus-response annotation, not a core catalytic or biosynthetic function of the enzyme; retained as non-core. |
| GO:0050992 dimethylallyl diphosphate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway-derived (UPA00059) electronic assignment. This is the precise process IDI1 performs — the single-step biosynthesis of DMAPP from IPP ("dimethylallyl diphosphate from isopentenyl diphosphate: step 1/1"). Correct core process; accepted. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt dimethylallyl diphosphate from isopentenyl diphosphate: |
| GO:0006695 cholesterol biosynthetic process | IC PMID:8806705 Human isopentenyl diphosphate: dimethylallyl diphosphate iso... | ACCEPT | Summary: Curator inference (IC, from the GO:0004452 activity) that IDI1 participates in cholesterol biosynthesis. The IPP/DMAPP interconversion is an essential activation step upstream of squalene and sterol synthesis, and IDI1 localizes to the pre-squalene peroxisomal segment of the cholesterol pathway (PMID:17180682). Correct core process; accepted. Supporting Evidence: PMID:8806705 Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes an essential activation step in the isoprenoid biosynthetic pathway. |
| GO:0004452 isopentenyl-diphosphate delta-isomerase activity | IDA PMID:8806705 Human isopentenyl diphosphate: dimethylallyl diphosphate iso... | ACCEPT | Summary: Direct experimental (IDA) demonstration of the core molecular function: recombinant human enzyme catalyzed isomerization of IPP to DMAPP, maximally active at pH 7.0 in the presence of Mg2+, Km(IPP)=33 uM. This is the definitive assay for the gene's core catalytic activity. Accepted as core. Supporting Evidence: PMID:8806705 recombinant protein catalyzed the isomerization of IPP to dimethylallyl diphosphate and was maximally active at pH 7.0 in the presence of Mg2+. |
| GO:0005777 peroxisome | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of peroxisomal localization from rat Idi1 (UniProtKB:O35586). Concordant with direct experimental human data (PMID:17180682, PMID:17202134) and the PTS1-type microbody targeting motif; accepted as a genuine location. Supporting Evidence: file:human/IDI1/IDI1-uniprot.txt SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:O35586} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1655823 | KEEP AS NON CORE | Summary: Reactome (TAS) cytosolic localization. Reactome models the IPP-to-DMAPP isomerase step as cytosolic (R-HSA-191382) while noting peroxisomal localization is also reported. Cytosolic activity of the mevalonate/isoprenoid pathway is well established, so this is retained as a genuine, if non-core, location alongside the peroxisome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-191382 | KEEP AS NON CORE | Summary: Reactome (TAS) cytosolic localization associated with the reaction event "Isopentenyl pyrophosphate rearranges to dimethylallyl pyrophosphate". Duplicate of the other Reactome cytosol annotation; retained as a genuine non-core location. |
| GO:0005777 peroxisome | IDA PMID:17180682 Localization of the pre-squalene segment of the isoprenoid b... | ACCEPT | Summary: Direct experimental (IDA) localization: immunofluorescence and cell-permeabilization analysis confirmed that the pre-squalene segment of the cholesterol biosynthetic pathway (which includes IDI1) localizes to peroxisomes in human cells. Accepted as a core location. Supporting Evidence: PMID:17180682 the pre-squalene segment of the cholesterol biosynthetic pathway is localized to peroxisomes |
| GO:0005777 peroxisome | IDA PMID:17202134 IDI2, a second isopentenyl diphosphate isomerase in mammals. | ACCEPT | Summary: Direct experimental (IDA) localization: IDI1 (and the paralog IDI2) shown to be targeted to the peroxisome via a PTS1-dependent pathway. Strong experimental support for peroxisomal localization of IDI1. Accepted as a core location. Supporting Evidence: PMID:17202134 Both isozymes, IDI1 and IDI2 are localized to the peroxisome by a PTS1-dependent pathway. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)