IDI2 (isopentenyl-diphosphate delta-isomerase 2) is a small (227 aa) metalloenzyme of the type-1 IPP isomerase family (Nudix hydrolase fold) and the paralog of IDI1. It catalyzes the reversible 1,3-allylic rearrangement that interconverts 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 the allylic isomer DMAPP, it supplies the primer that farnesyl diphosphate synthase and other prenyltransferases use to initiate prenyl-chain synthesis, feeding the sterol (cholesterol), dolichol, ubiquinone, and protein-prenylation branches of isoprenoid metabolism. Catalysis requires a divalent metal cofactor (Mg2+), and the enzyme carries a C-terminal PTS1-type microbody-targeting signal that directs it to the peroxisome. In contrast to the ubiquitously expressed IDI1, human IDI2 expression is restricted essentially to skeletal muscle, and it is regulated independently, possibly via PPARalpha.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment that IDI2 is active in the peroxisome. Concordant with the direct experimental localization of human IDI2 to the peroxisome via a PTS1-dependent pathway (PMID:17202134) and with the C-terminal PTS1-type microbody-targeting motif on the protein; retained as a genuine location. Supporting Evidence: file:human/IDI2/IDI2-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 IDI2, independently established by direct enzyme assay (PMID:17202134). Retained as core. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt Reaction=isopentenyl diphosphate = dimethylallyl diphosphate; |
| GO:0009240 isopentenyl diphosphate biosynthetic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA at PANTHER:PTN000853999 from Arabidopsis thaliana IPP1 (AGI_LocusCode:AT5G16440). In the mammalian mevalonate pathway, isopentenyl diphosphate (IPP) is synthesized by mevalonate diphosphate decarboxylase (MVD), and IDI2 isomerizes IPP to produce dimethylallyl diphosphate (DMAPP; GO:0050992) rather than synthesizing IPP. Reason: The PAINT node PANTHER:PTN000853999 is seeded from plant plastid/MEP-pathway curation (Arabidopsis IPP1, AGI_LocusCode:AT5G16440) where IPP/DMAPP equilibration is annotated under IPP biosynthesis. In the human mevalonate pathway, IPP is the substrate produced by MVD and DMAPP is the product of IDI2; the specific process GO:0050992 (dimethylallyl diphosphate biosynthetic process) is already present and ACCEPTed on this record, consistent with the curation of S. pombe idi1 and human IDI1. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000853999 · PTN000853999 SUPPORTS SOURCE BUT NOT TARGET Node carries GO:0009240 from Arabidopsis IPP1 (AGI_LocusCode:AT5G16440); in the mammalian mevalonate pathway IDI2 consumes IPP to synthesize DMAPP (GO:0050992). AGI_LocusCode:AT5G16440 · IPP1 SUPPORTS SOURCE BUT NOT TARGET Arabidopsis thaliana IPP1 donor for PTN000853999; in the human mevalonate pathway IPP is the substrate of IDI2 and DMAPP is the product (GO:0050992). Supporting Evidence: file:human/IDI2/IDI2-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/IDI2/IDI2-uniprot.txt EC=5.3.3.2 {ECO:0000269|PubMed:17202134} |
| 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:17202134) and the C-terminal PTS1-type microbody-targeting signal; accepted as a genuine location. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt MOTIF 225..227 |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the overarching isoprenoid biosynthetic process. IDI2 produces the DMAPP allylic primer required for prenyl-chain elongation, so this is a correct core process for the gene; accepted. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt PATHWAY: Isoprenoid biosynthesis |
| GO:0016860 intramolecular oxidoreductase activity | IEA GO_REF:0000117 | MODIFY | Summary: Electronic (ARBA) assignment to a general isomerase-branch parent term. Verified against go.db that GO:0004452 is a descendant of GO:0016860 (GO:0004452 -> GO:0016863 intramolecular oxidoreductase activity, transposing C=C bonds -> 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:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: High-throughput affinity-capture/interactome (IntAct) IPI annotation recording a binary interaction between IDI2 and LDB1 (isoform Q86U70-2), also captured in the UniProt INTERACTION block. Bare "protein binding" (GO:0005515) is uninformative about IDI2's molecular function, and no functional consequence of this interaction is established, so it is marked as an over-annotation rather than treated as a core function. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt Q9BXS1; Q86U70-2: LDB1; NbExp=4; IntAct=EBI-766127, EBI-11979761; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Yeast two-hybrid binary interactome (IntAct/HuRI) IPI annotation for the same IDI2-LDB1 (Q86U70-2) interaction recorded in the UniProt INTERACTION block. As a bare "protein binding" term with no established functional role, it is uninformative about IDI2's molecular function and is marked as an over-annotation. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt Q9BXS1; Q86U70-2: LDB1; NbExp=4; IntAct=EBI-766127, EBI-11979761; |
| GO:0050992 dimethylallyl diphosphate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway-derived (UPA00059) electronic assignment. This is the precise process IDI2 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/IDI2/IDI2-uniprot.txt dimethylallyl diphosphate from isopentenyl diphosphate: |
| GO:0004452 isopentenyl-diphosphate delta-isomerase activity | IDA PMID:17202134 IDI2, a second isopentenyl diphosphate isomerase in mammals. | ACCEPT | Summary: Direct experimental (IDA) demonstration of the core molecular function: partially purified human IDI2 catalyzed isomerization of [14C]IPP to [14C]DMAPP, with a maximal relative specific activity of 1.2 x 10^-1 umol/min/mg at pH 8.0 and Km(IPP)=22.8 uM, and human IDI2 complemented an idi1-deficient yeast strain. This is the definitive assay for the gene's core catalytic activity. Accepted as core. Supporting Evidence: PMID:17202134 IDI2 has the ability to catalyze the isomerization of [(14)C]IPP to [(14)C]DMAPP. |
| GO:0005777 peroxisome | IDA PMID:17202134 IDI2, a second isopentenyl diphosphate isomerase in mammals. | ACCEPT | Summary: Direct experimental (IDA) localization: IDI2 (and the paralog IDI1) shown to be targeted to the peroxisome via a PTS1-dependent pathway. Strong experimental support for peroxisomal localization; accepted as a core location. Supporting Evidence: PMID:17202134 Both isozymes, IDI1 and IDI2 are localized to the peroxisome by a PTS1-dependent pathway. |
| GO:0046490 isopentenyl diphosphate metabolic process | IDA PMID:17202134 IDI2, a second isopentenyl diphosphate isomerase in mammals. | MODIFY | Summary: Direct experimental (IDA) assignment of IPP metabolism, based on the demonstrated IPP-to-DMAPP isomerase activity of IDI2. Modified to the more specific process GO:0050992 (dimethylallyl diphosphate biosynthetic process), which is already present on this record. Reason: GO:0046490 (isopentenyl diphosphate metabolic process) is a general parent process; PMID:17202134 directly demonstrates isomerization of IPP to synthesize DMAPP, which is more precisely captured by GO:0050992 (dimethylallyl diphosphate biosynthetic process, already ACCEPTed on this record). Proposed replacements: dimethylallyl diphosphate biosynthetic process Supporting Evidence: PMID:17202134 IDI2 has the ability to catalyze the isomerization of [(14)C]IPP to [(14)C]DMAPP. |
| 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", which Reactome models as cytosolic while noting that IPP isomerase may also be peroxisomal. Cytosolic activity of the mevalonate/isoprenoid pathway is well established, so this is retained as a genuine, non-core location alongside the experimentally supported peroxisome. |
| GO:0008299 isoprenoid biosynthetic process | IDA PMID:17202134 IDI2, a second isopentenyl diphosphate isomerase in mammals. | ACCEPT | Summary: Direct experimental (IDA) assignment of the overarching isoprenoid biosynthetic process, based on the demonstrated IPP-to-DMAPP isomerase activity that primes prenyl-chain synthesis. Correct core process; accepted. Supporting Evidence: file:human/IDI2/IDI2-uniprot.txt PATHWAY: Isoprenoid biosynthesis |
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