id: Q13907
gene_symbol: IDI1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q13907-1
- name: '2'
  id: Q13907-2
  sequence_note: VSP_037889
existing_annotations:
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Peroxisome"
- term:
    id: GO:0004452
    label: isopentenyl-diphosphate delta-isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "Reaction=isopentenyl diphosphate = dimethylallyl diphosphate;"
- term:
    id: GO:0009240
    label: isopentenyl diphosphate biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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).
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "Reaction=isopentenyl diphosphate = dimethylallyl diphosphate;"
- term:
    id: GO:0004452
    label: isopentenyl-diphosphate delta-isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "EC=5.3.3.2 {ECO:0000269|PubMed:8806705}"
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "MOTIF           225..227"
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8806705
      supporting_text: "Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes an \nessential activation step in the isoprenoid biosynthetic pathway."
- term:
    id: GO:0016860
    label: intramolecular oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    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.
    action: MODIFY
    reason: >-
      Correct but overly general; the specific, experimentally established activity is
      isopentenyl-diphosphate delta-isomerase activity (GO:0004452).
    proposed_replacement_terms:
    - id: GO:0004452
      label: isopentenyl-diphosphate delta-isomerase activity
- term:
    id: GO:0035634
    label: response to stilbenoid
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0050992
    label: dimethylallyl diphosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "dimethylallyl diphosphate from isopentenyl diphosphate:"
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: IC
  original_reference_id: PMID:8806705
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8806705
      supporting_text: "Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes an \nessential activation step in the isoprenoid biosynthetic pathway."
- term:
    id: GO:0004452
    label: isopentenyl-diphosphate delta-isomerase activity
  evidence_type: IDA
  original_reference_id: PMID:8806705
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8806705
      supporting_text: "recombinant protein catalyzed the isomerization of IPP to dimethylallyl \ndiphosphate and was maximally active at pH 7.0 in the presence of Mg2+."
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IDI1/IDI1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:O35586}"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1655823
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191382
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:17180682
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17180682
      supporting_text: "the pre-squalene \nsegment of the cholesterol biosynthetic pathway is localized to peroxisomes"
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:17202134
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17202134
      supporting_text: "Both isozymes, IDI1 and IDI2 are localized \nto the peroxisome by a PTS1-dependent pathway."
core_functions:
- description: >-
    Catalyzes the reversible interconversion of isopentenyl diphosphate (IPP) and
    dimethylallyl diphosphate (DMAPP), producing the allylic DMAPP primer required to
    initiate isoprenoid/prenyl-chain biosynthesis. Requires a divalent metal cofactor
    (Mg2+).
  supported_by:
  - reference_id: PMID:8806705
    supporting_text: "recombinant protein catalyzed the isomerization of IPP to dimethylallyl \ndiphosphate and was maximally active at pH 7.0 in the presence of Mg2+."
  - reference_id: file:human/IDI1/IDI1-uniprot.txt
    supporting_text: "Reaction=isopentenyl diphosphate = dimethylallyl diphosphate;"
  molecular_function:
    id: GO:0004452
    label: isopentenyl-diphosphate delta-isomerase activity
  directly_involved_in:
  - id: GO:0050992
    label: dimethylallyl diphosphate biosynthetic process
  - id: GO:0008299
    label: isoprenoid biosynthetic process
  - id: GO:0006695
    label: cholesterol biosynthetic process
  locations:
  - id: GO:0005777
    label: peroxisome
  - id: GO:0005829
    label: cytosol
  substrates:
  - id: CHEBI:128769
    label: isopentenyl diphosphate(3-)
  - id: CHEBI:57623
    label: prenyl diphosphate(3-)
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:17180682
  title: Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway
    in mammalian peroxisomes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; abstract-only in cache. Supports peroxisomal localization of the
      pre-squalene cholesterol biosynthetic segment (including IDI1) in human cells; basis
      for the IDA peroxisome annotation.
- id: PMID:17202134
  title: IDI2, a second isopentenyl diphosphate isomerase in mammals.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; abstract-only. Although titled for the paralog IDI2, the abstract
      explicitly states both IDI1 and IDI2 are localized to the peroxisome by a
      PTS1-dependent pathway, directly supporting the IDI1 peroxisome IDA annotation.
- id: PMID:8806705
  title: 'Human isopentenyl diphosphate: dimethylallyl diphosphate isomerase: overproduction,
    purification, and characterization.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; abstract-only. Definitive biochemical characterization of
      recombinant human IDI1 (IPP->DMAPP isomerization, Mg2+ dependence, Km/Vmax);
      experimental basis for GO:0004452 (IDA) and the IC cholesterol biosynthesis
      annotation.
- id: Reactome:R-HSA-1655823
  title: Expression of Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)
  findings: []
- id: Reactome:R-HSA-191382
  title: Isopentenyl pyrophosphate rearranges to dimethylallyl pyrophosphate
  findings: []