IDI1

UniProt ID: P15496
Organism: Saccharomyces cerevisiae S288C
Review Status: COMPLETE
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Gene Description

IDI1 (BOT2, YPL117C) encodes the type I isopentenyl-diphosphate delta-isomerase of Saccharomyces cerevisiae, a Mg2+-dependent Nudix-fold enzyme that catalyses the reversible antarafacial [1,3]-allylic rearrangement of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP) (EC 5.3.3.2). In yeast IPP is made only by the mevalonate pathway (Erg19), so Idi1 is the source of the allylic DMAPP primer that Erg20 condenses with IPP to form geranyl and farnesyl diphosphate, and the enzyme is required for synthesis of ergosterol and all downstream isoprenoids. Cys139 is the active-site nucleophile and Glu207 is also essential for catalysis. Idi1 is a soluble cytosolic protein (with some nuclear signal in GFP surveys).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
EXP
PMID:2223785
Isopentenyldiphosphate:dimethylallyldiphosphate isomerase: c...
ACCEPT
Summary: Street & Poulter 1990 over-expressed yeast IPP isomerase in E. coli (>100,000-fold activity), purified it and identified Cys139 as the active-site nucleophile. Core MF.
Supporting Evidence:
PMID:2223785
IPP isomerase activity was increased by over 100,000-fold relative to that of the untransformed host strain
PMID:2223785
The primary site of attachment was Cys-139.
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
EXP
PMID:7908830
Identification of Cys139 and Glu207 as catalytically importa...
ACCEPT
Summary: Street et al. 1994 kinetic analysis of Idi1 site-directed mutants (C139, E207) of the IPP to DMAPP isomerisation. Core MF.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
PMID:7908830
The E207Q and E207V mutants were inactive, suggesting a role for the E207 carboxylate moiety in catalysis.
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from type I IDI node PTN000853999 (human IDI1/IDI2, mouse, Arabidopsis IPP1/IPP2, S. pombe, SGD Idi1). Correct.
Supporting Evidence:
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase) is an enzyme in the isoprenoid biosynthetic pathway which catalyzes the interconversion of the primary five-carbon homoallylic and allylic diphosphate building blocks.
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
IDA
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase....
ACCEPT
Summary: Anderson et al. 1989 purified IPP isomerase from yeast, sequenced it, cloned the gene and showed increased activity on over-expression. Core MF.
Supporting Evidence:
PMID:2681212
Upon transformation with plasmids containing the insert, a 5-6-fold increase in IPP isomerase activity was seen in transformed cells relative to YRp17 controls, confirming the identity of the cloned gene.
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined IEA (ARBA, InterPro IPR011876 IPP isomerase type 1, RHEA:23284, EC 5.3.3.2). Correct.
Supporting Evidence:
file:yeast/IDI1/IDI1-uniprot.txt
-!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 assignment of IPP <-> DMAPP. Correct.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways IPPSYN-PWY (mevalonate pathway) assignment. Correct.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways PWY-5123 (trans,trans-FPP biosynthesis) assignment. Correct.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0004452 isopentenyl-diphosphate delta-isomerase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways PWY-922 (mevalonate pathway I) assignment. Correct.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0005634 nucleus
HDA
PMID:14562095
Global analysis of protein localization in budding yeast.
KEEP AS NON CORE
Summary: Huh et al. 2003 GFP survey scored Idi1-GFP as cytoplasmic and nuclear. A small soluble protein can equilibrate into the nucleus; no nuclear function is known, so this is non-core.
Supporting Evidence:
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005737 cytoplasm
HDA
PMID:14562095
Global analysis of protein localization in budding yeast.
ACCEPT
Summary: Huh et al. 2003 GFP survey; cytoplasmic. Consistent with Idi1 being a soluble enzyme.
Supporting Evidence:
PMID:14562095
Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt subcellular location mapping (SL-0086, Cytoplasm). Correct.
Supporting Evidence:
file:yeast/IDI1/IDI1-uniprot.txt
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
GO:0005773 vacuole
NAS
PMID:28904410
Recent Advances in Ergosterol Biosynthesis and Regulation Me...
MARK AS OVER ANNOTATED
Summary: Vacuole NAS from the Hu et al. 2017 ergosterol review, echoed in UniProt's function text ("the second module is carried out in the vacuole"). No primary data place Idi1 in the vacuole; GFP surveys place it in the cytosol (and nucleus).
Reason: Review-level statement without primary support, at odds with GFP localisation data.
Supporting Evidence:
file:yeast/IDI1/IDI1-uniprot.txt
module is carried out in the vacuole and involves the formation of
PMID:28904410
The biosynthesis of ergosterol can be divided into three modules: mevalonate, farnesyl pyrophosphate (farnesyl-PP) and ergosterol biosynthesis.
GO:0005829 cytosol
HDA
PMID:26928762
One library to make them all: streamlining the creation of y...
ACCEPT
Summary: Yofe et al. 2016 SWAT N-terminal GFP library scored Idi1 as cytosolic. Correct.
Supporting Evidence:
PMID:26928762
we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 cytosolic compartment; correct for Idi1.
Supporting Evidence:
PMID:26928762
we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways IPPSYN-PWY cytosolic compartment; correct.
Supporting Evidence:
PMID:26928762
we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways PWY-5123 cytosolic compartment; correct.
Supporting Evidence:
PMID:26928762
we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins
GO:0005829 cytosol
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways PWY-922 cytosolic compartment; correct.
Supporting Evidence:
PMID:26928762
we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins
GO:0006696 ergosterol biosynthetic process
IDA
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase....
ACCEPT
Summary: Anderson et al. 1989 identify IPP isomerase as an enzyme of the isoprenoid (sterol) pathway; Idi1 catalyses a step of the yeast mevalonate/ergosterol pathway (DMAPP supply). Correct; the more specific process is DMAPP biosynthesis.
Supporting Evidence:
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase) is an enzyme in the isoprenoid biosynthetic pathway which catalyzes the interconversion of the primary five-carbon homoallylic and allylic diphosphate building blocks.
GO:0006696 ergosterol biosynthetic process
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 membership. Idi1 catalyses a step of this pathway. Correct.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0008299 isoprenoid biosynthetic process
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro IPR011876 mapping to isoprenoid biosynthetic process. Correct, general.
Supporting Evidence:
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase) is an enzyme in the isoprenoid biosynthetic pathway which catalyzes the interconversion of the primary five-carbon homoallylic and allylic diphosphate building blocks.
GO:0008299 isoprenoid biosynthetic process
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways IPPSYN-PWY membership. Correct, general.
Supporting Evidence:
PMID:2681212
Isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase) is an enzyme in the isoprenoid biosynthetic pathway which catalyzes the interconversion of the primary five-carbon homoallylic and allylic diphosphate building blocks.
GO:0009240 isopentenyl diphosphate biosynthetic process
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: IBA from the eukaryotic Type I IDI root node PANTHER:PTN000853999 (from Arabidopsis IPP1, AGI_LocusCode:AT5G16440). In plastids the MEP pathway makes both IPP and DMAPP and IDI can run DMAPP -> IPP, so IPP biosynthesis is meaningful there. In S. cerevisiae IPP is made exclusively by Erg19 (mevalonate pathway) and Idi1 converts it to DMAPP, so the yeast enzyme consumes rather than produces IPP. The reaction is reversible, so the term is not strictly wrong, but it misrepresents Idi1's physiological role.
Reason: PANTHER:PTN000853999 (which has an empty taxon field in the PTHR10885 PAINT file) spans plastidial MEP-pathway and cytosolic/peroxisomal mevalonate-pathway Type I IDI enzymes across plants, fungi, and metazoans (as reflected by its GO:0004452 IBD donors AT3G02780, AT5G16440, MGI:2442264, SPBC106.15, S000006038, Q13907, and Q9BXS1). In S. cerevisiae, diphosphomevalonate decarboxylase (Erg19) synthesizes IPP exclusively via the mevalonate pathway, and Idi1 catalyzes its isomerization to DMAPP (GO:0004452 / GO:0050992 dimethylallyl diphosphate biosynthetic process). Treating IPP as the biosynthetic product (GO:0009240) reflects plastidial MEP-pathway context (Arabidopsis IPP1, AGI_LocusCode:AT5G16440) rather than yeast physiological flux, matching sibling reviews human/IDI1, human/IDI2, and SCHPO/idi1.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: FUNCTIONAL DIVERGENCE ROLE CONFLATION
Sources checked:
PANTHER:PTN000853999 Β· PTN000853999 SUPPORTS SOURCE BUT NOT TARGET
Root Type I IDI node in PTHR10885 (empty taxon field in the PAINT file; spanning plant, fungal, and metazoan GO:0004452 IBD donors) groups plastidial MEP-pathway and cytosolic/peroxisomal MVA-pathway enzymes; in yeast MVA metabolism, IPP is the substrate produced by Erg19 and DMAPP is the product of Idi1.
AGI_LocusCode:AT5G16440 Β· Arabidopsis thaliana IPP1 SUPPORTS SOURCE BUT NOT TARGET
Arabidopsis IPP1 participates in plant isoprenoid metabolism where plastidial MEP enzymes co-produce IPP and DMAPP; yeast Idi1 operates exclusively in the MVA pathway converting IPP to DMAPP.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
file:yeast/IDI1/IDI1-uniprot.txt
-!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process
IDA
PMID:7858969
Enzymatic synthesis of isotopically labeled isoprenoid dipho...
KEEP AS NON CORE
Summary: Christensen & Poulter 1994 used recombinant yeast Idi1 together with avian FPPS to make labelled FPP in vitro. Idi1 supplies DMAPP, the allylic primer for FPP synthesis, a genuine step in the FPP pathway (MetaCyc PWY-5123 includes it), but the condensations are carried out by FPPS (Erg20).
Supporting Evidence:
PMID:7858969
Recombinant yeast isopentenyl diphosphate (IPP) isomerase and avian farnesyl diphosphate (FPP) synthase from overproducing strains of Escherichia coli were used to synthesize FPP from IPP and dimethylallyl diphosphate (DMAPP).
GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process
RCA
GO_REF:0000123
KEEP AS NON CORE
Summary: YeastPathways PWY-5123 (trans,trans-FPP biosynthesis) membership; the pathway includes the IDI step. Acceptable but non-core; DMAPP biosynthesis is the direct process.
Supporting Evidence:
PMID:7858969
Recombinant yeast isopentenyl diphosphate (IPP) isomerase and avian farnesyl diphosphate (FPP) synthase from overproducing strains of Escherichia coli were used to synthesize FPP from IPP and dimethylallyl diphosphate (DMAPP).
GO:0050992 dimethylallyl diphosphate biosynthetic process
IEA
GO_REF:0000041
ACCEPT
Summary: UniPathway UPA00059 (DMAPP biosynthesis from IPP, step 1/1) mapping. This is exactly Idi1's role; core process.
Supporting Evidence:
file:yeast/IDI1/IDI1-uniprot.txt
-!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
GO:0050993 dimethylallyl diphosphate metabolic process
IEA
GO_REF:0000117
MODIFY
Summary: ARBA annotation to the DMAPP metabolic process parent. Correct but less specific than the biosynthetic term, which is already annotated.
Supporting Evidence:
PMID:7908830
catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)

Core Functions

IPP isomerisation: Mg2+-dependent [1,3]-allylic rearrangement of isopentenyl diphosphate to dimethylallyl diphosphate (EC 5.3.3.2), supplying the allylic primer for Erg20 prenyl chain elongation and hence for ergosterol and all yeast isoprenoids.

Supporting Evidence:
  • PMID:7908830
    catalyzes the antarafacial [1.3] allylic rearrangement of isopentenyl diphosphate (IPP) to its electrophilic allylic isomer dimethylallyl diphosphate (DMAPP)
  • PMID:2681212
    Upon transformation with plasmids containing the insert, a 5-6-fold increase in IPP isomerase activity was seen in transformed cells relative to YRp17 controls, confirming the identity of the cloned gene.
  • PMID:2223785
    The primary site of attachment was Cys-139.
  • PMID:26928762
    we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins

References

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Suggested Questions for Experts

Q: Is there any primary evidence for a vacuolar pool of Idi1 (or Erg20) supporting the "second module in the vacuole" statement propagated from the Hu et al. 2017 review into UniProt and GO?

Suggested Experiments

Experiment: Quantify the nuclear Idi1-GFP pool and test whether it has any function, e.g. by tethering Idi1 to the cytosol with an NES and assaying growth and sterol levels.

Deep Research

SGD

(IDI1-deep-research-sgd.md)
SGD gene description for IDI1 (yeast) SGD

SGD gene description for IDI1 (yeast)

Isopentenyl diphosphate:dimethylallyl diphosphate isomerase; catalyzes an essential activation step in the isoprenoid biosynthetic pathway; required for viability; isopentenyl diphosphate:dimethylallyl diphosphate isomerase is also known as IPP isomerase

πŸ“š Additional Documentation

Notes

(IDI1-notes.md)

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