Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1; EC 1.1.1.205) catalyses the NAD+-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP) (IMP + NAD+ + H2O -> XMP + NADH + H+), the first committed and rate-limiting step of de novo guanine-nucleotide (GMP) biosynthesis; XMP is subsequently aminated to GMP by GMP synthase (GMPS). The enzyme is a cytosolic homotetramer built from a catalytic (beta/alpha)8 TIM-barrel domain plus a regulatory subdomain of two tandem CBS (Bateman) domains, uses a monovalent cation (K+) cofactor, and can assemble into higher-order filaments ("rods and rings"/cytoophidia). IMPDH1 is broadly expressed but strongly enriched in retinal photoreceptors; a reported single-stranded nucleic-acid-binding activity mediated by the CBS subdomain suggests an additional, less well-defined role in nucleic-acid metabolism. Because guanine-nucleotide supply is coupled to cell proliferation, IMPDH is a validated target of immunosuppressive (mycophenolic acid, mizoribine), antiviral (ribavirin) and antitumour drugs. Dominant IMPDH1 mutations, many clustered in the CBS subdomain, cause retinitis pigmentosa 10 (RP10) and Leber congenital amaurosis (LCA11), degenerative diseases of the retina.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005737
cytoplasm
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Phylogenetically inferred cytoplasmic localization. IMPDH1 is a soluble cytosolic enzyme, consistent with its role in the cytosolic de novo purine pathway.
Reason: IBA is_active_in cytoplasm is correct and consistent with the UniProt subcellular location and with the more specific IDA cytosol annotation. This is a core localization for the enzyme's catalytic activity.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0003938
IMP dehydrogenase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IMP dehydrogenase activity (EC 1.1.1.205) is the defining, experimentally and phylogenetically well-supported molecular function of IMPDH1: NAD+-dependent oxidation of IMP to XMP.
Reason: This is the core molecular function. Supported by the enzyme name, EC number, catalytic-activity reaction in UniProt, and by direct biochemical characterization of human type I IMPDH; the IBA is at the correct level of specificity.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)
PMID:1969416
IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP
|
|
GO:0006183
GTP biosynthetic process
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: IMPDH1 contributes to GTP biosynthesis only indirectly: it makes XMP (->GMP), and GMP is subsequently phosphorylated (GMP->GDP->GTP) by other enzymes.
Reason: The direct committed step catalysed by IMPDH1 produces XMP en route to GMP, not GTP. GTP biosynthesis is several enzymatic steps downstream, so this term overstates the enzyme's direct role. It is biologically defensible as a broader pathway contribution but is not the core function; the more precise BP terms are XMP/GMP biosynthetic process.
Supporting Evidence:
PMID:1969416
IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP
|
|
GO:0000166
nucleotide binding
|
IEA
GO_REF:0000104 |
MODIFY |
Summary: IMPDH1 binds the nucleotide cofactor NAD+ and the nucleotide substrate IMP; a generic "nucleotide binding" annotation captures this but at a very shallow level.
Reason: The term is not wrong but is uninformative given that the specific ligands (NAD+, IMP) and the catalytic activity are known. Replace with the specific cofactor-binding molecular function NAD binding (GO:0051287); the catalytic activity term already covers IMP as substrate.
Proposed replacements:
NAD binding
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)
|
|
GO:0003824
catalytic activity
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: Root-level catalytic activity term derived from an InterPro domain mapping. IMPDH1 is an enzyme, so this is true but maximally uninformative.
Reason: "catalytic activity" is the top of the MF catalytic branch and adds nothing beyond the specific, well-established IMP dehydrogenase activity. Replace with GO:0003938 (IMP dehydrogenase activity).
Proposed replacements:
IMP dehydrogenase activity
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)
|
|
GO:0003938
IMP dehydrogenase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Electronic (UniRule/RHEA/EC-based) assertion of the core IMP dehydrogenase activity, duplicating the IBA and TAS annotations of the same term.
Reason: Correct and specific core molecular function; the IEA mapping from EC 1.1.1.205 / RHEA:11708 is well grounded. Duplicate of GO:0003938 by other evidence codes, which is acceptable.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000120 |
KEEP AS NON CORE |
Summary: Nuclear localization transferred electronically, ultimately reflecting the reported nuclear pool of IMPDH linked to its nucleic-acid-binding activity.
Reason: IMPDH is detected in the nucleus (PMID:14766016), but the enzyme's core catalytic role in de novo GMP synthesis operates in the cytosol. Nuclear localization relates to the moonlighting single-stranded nucleic-acid-binding activity and is a non-core feature.
Supporting Evidence:
PMID:14766016
IMPDH is found in the nucleus of human cells, as
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Electronic cytoplasmic localization, consistent with the enzyme's soluble cytosolic distribution.
Reason: Correct core localization; duplicates the IBA/IDA cytoplasm and IDA cytosol annotations. The cytosol is where IMPDH1 performs its catalytic function.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0006164
purine nucleotide biosynthetic process
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: Broad "purine nucleotide biosynthetic process" from an InterPro mapping. IMPDH1 does act in de novo purine (guanine) nucleotide biosynthesis, but this is a high-level parent term.
Reason: Correct branch but too general; the specific, well-defined role is in guanosine (GMP)/XMP biosynthesis. Replace with the more precise GMP biosynthetic process (GO:0006177), which is the committed step catalysed by IMPDH1.
Proposed replacements:
GMP biosynthetic process
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
step in the de novo synthesis of guanine nucleotides
|
|
GO:0006177
GMP biosynthetic process
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: GMP biosynthetic process, the pathway in which IMPDH1 catalyses the committed, rate-limiting step (IMP -> XMP -> GMP).
Reason: This is the correct, appropriately specific core biological process for IMPDH1. The enzyme makes XMP, the immediate committed precursor of GMP, in the de novo guanine-nucleotide pathway.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
step in the de novo synthesis of guanine nucleotides
|
|
GO:0016491
oxidoreductase activity
|
IEA
GO_REF:0000002 |
MODIFY |
Summary: Parent oxidoreductase activity from an InterPro mapping. IMPDH1 is an NAD+-dependent oxidoreductase, but this is a broad ancestor of its specific activity.
Reason: True but too general; the specific dehydrogenase activity is IMP dehydrogenase activity (GO:0003938), a descendant of oxidoreductase activity. Replace with the specific term.
Proposed replacements:
IMP dehydrogenase activity
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)
|
|
GO:0046872
metal ion binding
|
IEA
GO_REF:0000104 |
MODIFY |
Summary: Metal-ion binding assigned by UniRule. IMPDH1 requires a monovalent cation (K+) cofactor, with several structurally defined K+ binding sites at the tetramer interface.
Reason: The generic "metal ion binding" understates the specific, functionally important requirement for a monovalent cation (potassium). Replace with potassium ion binding (GO:0030955), which the UniProt COFACTOR and K+ BINDING site annotations support.
Proposed replacements:
potassium ion binding
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
Name=K(+)
|
|
GO:0097294
'de novo' XMP biosynthetic process
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: 'de novo' XMP biosynthetic process is the most precise biological process for the reaction IMPDH1 actually catalyses: IMP -> XMP is the single committed step of de novo XMP synthesis.
Reason: Directly matches the UniProt pathway annotation ("XMP biosynthesis via de novo pathway; XMP from IMP: step 1/1") and the catalytic reaction. This is arguably the single most accurate BP term for IMPDH1 and a core process.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
XMP biosynthesis via de novo pathway
|
|
GO:0005829
cytosol
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: Direct immunofluorescence localization (HPA) to the cytosol, the compartment where IMPDH1 carries out de novo GMP synthesis.
Reason: Experimental (IDA) cytosolic localization is the most specific and accurate core location, consistent with the soluble cytosolic purine pathway and the broader cytoplasm annotations.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0005576
extracellular region
|
TAS
Reactome:R-HSA-6798748 |
MARK AS OVER ANNOTATED |
Summary: Extracellular localization inferred from a Reactome neutrophil-degranulation exocytosis event (secretory granule proteins), not from a dedicated function of IMPDH1.
Reason: IMPDH1 is a soluble cytosolic enzyme. Its appearance in the extracellular region derives from bulk proteomic detection of the neutrophil granule/secretome and does not reflect a genuine secreted function. This is a bystander over-annotation, not a core localization.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0005576
extracellular region
|
TAS
Reactome:R-HSA-6798751 |
MARK AS OVER ANNOTATED |
Summary: Duplicate extracellular-region localization from a Reactome azurophil-granule exocytosis event.
Reason: Same rationale as the other extracellular-region Reactome annotations: IMPDH1 is cytosolic, and its granule-lumen/extracellular assignment reflects neutrophil-degranulation proteomics rather than a genuine secreted role.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0005576
extracellular region
|
TAS
Reactome:R-HSA-6800434 |
MARK AS OVER ANNOTATED |
Summary: Duplicate extracellular-region localization from a Reactome ficolin-rich granule exocytosis event.
Reason: As with the other Reactome degranulation-derived localizations, this reflects bulk granule/secretome proteomics rather than a genuine extracellular function of the cytosolic enzyme IMPDH1.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0034774
secretory granule lumen
|
TAS
Reactome:R-HSA-6798748 |
MARK AS OVER ANNOTATED |
Summary: Secretory granule lumen localization from the Reactome neutrophil-degranulation pathway.
Reason: Cytosolic IMPDH1 is detected in neutrophil granule proteomes, but this is a bystander/contaminant-type localization from degranulation datasets rather than a genuine granule-lumen residence relevant to its enzymatic function.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0035578
azurophil granule lumen
|
TAS
Reactome:R-HSA-6798751 |
MARK AS OVER ANNOTATED |
Summary: Azurophil granule lumen localization from the Reactome neutrophil-degranulation pathway.
Reason: As above: derives from neutrophil granule proteomics of the cytosolic enzyme IMPDH1 and does not reflect a core, functionally meaningful granule-lumen localization.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:1904813
ficolin-1-rich granule lumen
|
TAS
Reactome:R-HSA-6800434 |
MARK AS OVER ANNOTATED |
Summary: Ficolin-1-rich granule lumen localization from the Reactome neutrophil-degranulation pathway.
Reason: Same bystander-proteomics rationale: cytosolic IMPDH1 appearing in a granule lumen dataset does not constitute a genuine, core subcellular location for the enzyme.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-73794 |
ACCEPT |
Summary: Cytosolic localization asserted by the Reactome IMP -> XMP reaction, the core catalytic event of IMPDH1.
Reason: Correct core localization tied directly to the catalytic reaction; consistent with the IDA cytosol and cytoplasm annotations.
Supporting Evidence:
Reactome:R-HSA-73794
IMP dehydrogenase 1 and 2 (IMPDH1,2) catalyze the irreversible dehydrogenation of inosine 5'-monophosphate (IMP) to form xanthosine 5'-monophosphate (XMP)
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9678749 |
ACCEPT |
Summary: Cytosolic localization from the Reactome "IMPDH tetramers bind IMPDH inhibitors" reaction (drug-binding context).
Reason: The cytosol is the correct core compartment for IMPDH1; the annotation arises from a drug/inhibitor-binding reaction but the localization itself is accurate and duplicates the other cytosol annotations.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9748945 |
ACCEPT |
Summary: Cytosolic localization from the Reactome "IMPDH tetramers dehydrogenate 6TIMP to 6TXMP" reaction (thiopurine metabolism context).
Reason: Correct core localization. The reaction reflects IMPDH turnover of a thiopurine metabolite, but the cytosolic assignment is accurate and duplicates the other cytosol annotations.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0003676
nucleic acid binding
|
IDA
PMID:14766016 Inosine 5'-monophosphate dehydrogenase binds nucleic acids i... |
KEEP AS NON CORE |
Summary: Direct demonstration that IMPDH (both human isoforms) binds single-stranded nucleic acids with nanomolar affinity via its CBS subdomain, with ~100 nucleotides bound per tetramer.
Reason: This is a genuine, experimentally supported moonlighting activity of IMPDH1 mediated by the regulatory CBS (Bateman) subdomain, and several RP10/LCA disease variants alter this nucleic-acid affinity. However, the enzyme's core function is IMP dehydrogenase catalysis; the nucleic-acid-binding role is regulatory/moonlighting and best retained as non-core.
Supporting Evidence:
PMID:14766016
bind single-stranded nucleic acids with nanomolar affinity via the
|
|
GO:0003677
DNA binding
|
IDA
PMID:14766016 Inosine 5'-monophosphate dehydrogenase binds nucleic acids i... |
KEEP AS NON CORE |
Summary: IMPDH was shown by immunoprecipitation to bind DNA (and RNA) in vivo, an extension of its single-stranded nucleic-acid-binding activity.
Reason: Experimentally supported (IDA) but represents the moonlighting nucleic-acid interaction rather than a sequence-specific transcription-factor-type DNA binding. It is a non-core, regulatory activity distinct from the enzyme's committed metabolic role; retained as non-core per curation policy for experimental annotations.
Supporting Evidence:
PMID:14766016
immunoprecipitation experiments show that IMPDH binds both RNA and DNA in vivo
|
|
GO:0005634
nucleus
|
IDA
PMID:14766016 Inosine 5'-monophosphate dehydrogenase binds nucleic acids i... |
KEEP AS NON CORE |
Summary: Direct detection of IMPDH in the nucleus of human cells, consistent with its nucleic-acid-binding activity.
Reason: Experimentally supported nuclear pool, but the enzyme's core catalytic function in de novo GMP synthesis is cytosolic. Nuclear localization is tied to the moonlighting nucleic-acid-binding role and is non-core.
Supporting Evidence:
PMID:14766016
IMPDH is found in the nucleus of human cells, as
|
|
GO:0005737
cytoplasm
|
IDA
PMID:14766016 Inosine 5'-monophosphate dehydrogenase binds nucleic acids i... |
ACCEPT |
Summary: Direct localization of IMPDH to the cytoplasm, its principal compartment.
Reason: Experimental (IDA) cytoplasmic localization corroborates the core cytosolic residence where IMPDH1 catalyses IMP -> XMP; consistent with the IDA cytosol and IBA/IEA cytoplasm annotations.
Supporting Evidence:
file:human/IMPDH1/IMPDH1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
|
|
GO:0003938
IMP dehydrogenase activity
|
TAS
PMID:1969416 Two distinct cDNAs for human IMP dehydrogenase. |
ACCEPT |
Summary: Traceable author statement (original cloning paper) that the two human IMPDH cDNAs encode IMP dehydrogenase, the rate-limiting enzyme of de novo guanine nucleotide synthesis.
Reason: Core molecular function supported by the foundational cloning/characterization paper for human IMPDH1 (type I). Duplicates GO:0003938 by other evidence codes, which is acceptable.
Supporting Evidence:
PMID:1969416
IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP
|
Q: Is the single-stranded nucleic-acid-binding activity of the CBS subdomain a physiologically regulated function of IMPDH1 in photoreceptors, and does its disruption (as by RP10/LCA CBS-domain variants) cause disease independently of catalytic activity?
Q: What is the functional significance of IMPDH1 filament ("rods and rings"/ cytoophidia) assembly for guanine-nucleotide homeostasis in the retina?
Experiment: Separate-of-function IMPDH1 alleles that abolish catalysis while preserving nucleic-acid binding (and vice versa) expressed in photoreceptor models, to test whether RP10/LCA phenotypes arise from loss of catalysis, loss/alteration of nucleic-acid binding, or a dominant-negative filament defect.
Experiment: Cryo-EM and cellular imaging of retina-specific IMPDH1 isoforms to determine how the extended N-terminal retinal isoforms modulate filament assembly and GTP/GDP-dependent allosteric regulation.
IMPDH1 = inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205). Catalyzes the
committed, rate-limiting step of de novo guanine-nucleotide synthesis:
IMP + NAD+ + H2O -> XMP + NADH + H+ (RHEA:11708). XMP is then aminated to GMP by
GMPS. UniProt FUNCTION: "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:14766016 (McLean et al. 2004, abstract only): IMPDHs (T. foetus, E. coli, both human
isoforms) bind single-stranded nucleic acids with nanomolar affinity via the CBS subdomain;
~100 nt per tetramer. IMPDH found in nucleus; immunoprecipitation shows binding of RNA and
DNA in vivo. Concluded "a previously unappreciated role in replication, transcription or
translation." This is a moonlighting/regulatory activity, NOT the core catalytic function.
UniProt hedges: "Could also have a single-stranded nucleic acid-binding activity and could
play a role in RNA and/or DNA metabolism." => treat DNA/nucleic-acid binding and the nucleus
localization associated with it as KEEP_AS_NON_CORE.
Core MF: GO:0003938 IMP dehydrogenase activity (IBA, IEA, TAS PMID:1969416).
Core BP: GO:0006177 GMP biosynthetic process (IEA); GO:0097294 'de novo' XMP biosynthetic
process (IEA/Ensembl orthology) — most precise BP for the actual reaction; GO:0006183 GTP
biosynthetic process (IBA) — one step removed (XMP->GMP->GDP->GTP), keep as non-core;
GO:0006164 purine nucleotide biosynthetic process (IEA, broad parent).
CC: GO:0005829 cytosol (IDA HPA; TAS Reactome) — core location; GO:0005737 cytoplasm
(IBA is_active_in, IEA, IDA) — core; GO:0005634 nucleus (IEA, IDA PMID:14766016) — non-core
moonlighting. Extracellular/granule-lumen (Reactome neutrophil degranulation) = bystander
secretome, non-core.
R-HSA-73794 is the actual IMP->XMP reaction (core). R-HSA-9678749/9748945 concern IMPDH
inhibitor binding / thiopurine (6TIMP) turnover (drug-metabolism context). R-HSA-6798748/
6798751/6800434 are neutrophil-degranulation exocytosis events (extracellular/granule lumen
localization by mass-spec proteomics of granules) — bystander, non-core.
id: P20839
gene_symbol: IMPDH1
product_type: PROTEIN
status: INITIALIZED
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1; EC 1.1.1.205) catalyses the
NAD+-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine
5'-monophosphate (XMP) (IMP + NAD+ + H2O -> XMP + NADH + H+), the first
committed and rate-limiting step of de novo guanine-nucleotide (GMP)
biosynthesis; XMP is subsequently aminated to GMP by GMP synthase (GMPS). The
enzyme is a cytosolic homotetramer built from a catalytic (beta/alpha)8 TIM-barrel
domain plus a regulatory subdomain of two tandem CBS (Bateman) domains, uses a
monovalent cation (K+) cofactor, and can assemble into higher-order filaments
("rods and rings"/cytoophidia). IMPDH1 is broadly expressed but strongly enriched
in retinal photoreceptors; a reported single-stranded nucleic-acid-binding
activity mediated by the CBS subdomain suggests an additional, less well-defined
role in nucleic-acid metabolism. Because guanine-nucleotide supply is coupled to
cell proliferation, IMPDH is a validated target of immunosuppressive (mycophenolic
acid, mizoribine), antiviral (ribavirin) and antitumour drugs. Dominant IMPDH1
mutations, many clustered in the CBS subdomain, cause retinitis pigmentosa 10
(RP10) and Leber congenital amaurosis (LCA11), degenerative diseases of the retina.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000104
title: Electronic Gene Ontology annotations created by transferring manual GO annotations
between related proteins based on shared sequence features
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to
orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:14766016
title: Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in
vivo.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
PubMed-verified (Hedstrom lab, Biochem J 2004). Establishes the CBS-subdomain
single-stranded nucleic-acid-binding activity for both human IMPDH isoforms
and IMPDH nuclear localization. Supports a moonlighting/regulatory (non-core)
role rather than the enzyme's principal catalytic function; abstract-only in
the cache.
- id: PMID:1969416
title: Two distinct cDNAs for human IMP dehydrogenase.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified (Natsumeda et al., J Biol Chem 1990). Original cloning of the
two human IMPDH cDNAs (type I = IMPDH1, type II = IMPDH2); identifies IMP
dehydrogenase (EC 1.1.1.205) as the rate-limiting enzyme of de novo guanine
nucleotide biosynthesis. Directly supports the core catalytic function.
- id: Reactome:R-HSA-6798748
title: Exocytosis of secretory granule lumen proteins
findings: []
- id: Reactome:R-HSA-6798751
title: Exocytosis of azurophil granule lumen proteins
findings: []
- id: Reactome:R-HSA-6800434
title: Exocytosis of ficolin-rich granule lumen proteins
findings: []
- id: Reactome:R-HSA-73794
title: IMP + H2O + NAD+ => XMP + NADH + H+ [IMPDH1,2]
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
Reactome reaction for the human IMP -> XMP dehydrogenation catalysed by IMPDH1
and IMPDH2; the summary confirms this is the rate-limiting step in GMP synthesis
from IMP. Directly supports the core molecular function.
- id: Reactome:R-HSA-9678749
title: IMPDH tetramers bind IMPDH inhibitors
findings: []
- id: Reactome:R-HSA-9748945
title: IMPDH tetramers dehydrogenate 6TIMP to 6TXMP
findings: []
- id: file:human/IMPDH1/IMPDH1-uniprot.txt
title: UniProtKB P20839 (IMDH1_HUMAN) curated entry
findings: []
existing_annotations:
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: >-
Phylogenetically inferred cytoplasmic localization. IMPDH1 is a soluble
cytosolic enzyme, consistent with its role in the cytosolic de novo purine
pathway.
action: ACCEPT
reason: >-
IBA is_active_in cytoplasm is correct and consistent with the UniProt
subcellular location and with the more specific IDA cytosol annotation. This
is a core localization for the enzyme's catalytic activity.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0003938
label: IMP dehydrogenase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: >-
IMP dehydrogenase activity (EC 1.1.1.205) is the defining, experimentally and
phylogenetically well-supported molecular function of IMPDH1: NAD+-dependent
oxidation of IMP to XMP.
action: ACCEPT
reason: >-
This is the core molecular function. Supported by the enzyme name, EC number,
catalytic-activity reaction in UniProt, and by direct biochemical
characterization of human type I IMPDH; the IBA is at the correct level of
specificity.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- reference_id: PMID:1969416
supporting_text: "IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP"
- term:
id: GO:0006183
label: GTP biosynthetic process
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: >-
IMPDH1 contributes to GTP biosynthesis only indirectly: it makes XMP (->GMP),
and GMP is subsequently phosphorylated (GMP->GDP->GTP) by other enzymes.
action: KEEP_AS_NON_CORE
reason: >-
The direct committed step catalysed by IMPDH1 produces XMP en route to GMP,
not GTP. GTP biosynthesis is several enzymatic steps downstream, so this term
overstates the enzyme's direct role. It is biologically defensible as a broader
pathway contribution but is not the core function; the more precise BP terms are
XMP/GMP biosynthetic process.
supported_by:
- reference_id: PMID:1969416
supporting_text: "IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP"
- term:
id: GO:0000166
label: nucleotide binding
evidence_type: IEA
original_reference_id: GO_REF:0000104
qualifier: enables
review:
summary: >-
IMPDH1 binds the nucleotide cofactor NAD+ and the nucleotide substrate IMP; a
generic "nucleotide binding" annotation captures this but at a very shallow
level.
action: MODIFY
reason: >-
The term is not wrong but is uninformative given that the specific ligands
(NAD+, IMP) and the catalytic activity are known. Replace with the specific
cofactor-binding molecular function NAD binding (GO:0051287); the catalytic
activity term already covers IMP as substrate.
proposed_replacement_terms:
- id: GO:0051287
label: NAD binding
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- term:
id: GO:0003824
label: catalytic activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
Root-level catalytic activity term derived from an InterPro domain mapping.
IMPDH1 is an enzyme, so this is true but maximally uninformative.
action: MODIFY
reason: >-
"catalytic activity" is the top of the MF catalytic branch and adds nothing
beyond the specific, well-established IMP dehydrogenase activity. Replace with
GO:0003938 (IMP dehydrogenase activity).
proposed_replacement_terms:
- id: GO:0003938
label: IMP dehydrogenase activity
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- term:
id: GO:0003938
label: IMP dehydrogenase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: >-
Electronic (UniRule/RHEA/EC-based) assertion of the core IMP dehydrogenase
activity, duplicating the IBA and TAS annotations of the same term.
action: ACCEPT
reason: >-
Correct and specific core molecular function; the IEA mapping from EC 1.1.1.205
/ RHEA:11708 is well grounded. Duplicate of GO:0003938 by other evidence codes,
which is acceptable.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: >-
Nuclear localization transferred electronically, ultimately reflecting the
reported nuclear pool of IMPDH linked to its nucleic-acid-binding activity.
action: KEEP_AS_NON_CORE
reason: >-
IMPDH is detected in the nucleus (PMID:14766016), but the enzyme's core
catalytic role in de novo GMP synthesis operates in the cytosol. Nuclear
localization relates to the moonlighting single-stranded nucleic-acid-binding
activity and is a non-core feature.
supported_by:
- reference_id: PMID:14766016
supporting_text: "IMPDH is found in the nucleus of human cells, as"
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: >-
Electronic cytoplasmic localization, consistent with the enzyme's soluble
cytosolic distribution.
action: ACCEPT
reason: >-
Correct core localization; duplicates the IBA/IDA cytoplasm and IDA cytosol
annotations. The cytosol is where IMPDH1 performs its catalytic function.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0006164
label: purine nucleotide biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: >-
Broad "purine nucleotide biosynthetic process" from an InterPro mapping.
IMPDH1 does act in de novo purine (guanine) nucleotide biosynthesis, but this
is a high-level parent term.
action: MODIFY
reason: >-
Correct branch but too general; the specific, well-defined role is in guanosine
(GMP)/XMP biosynthesis. Replace with the more precise GMP biosynthetic process
(GO:0006177), which is the committed step catalysed by IMPDH1.
proposed_replacement_terms:
- id: GO:0006177
label: GMP biosynthetic process
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "step in the de novo synthesis of guanine nucleotides"
- term:
id: GO:0006177
label: GMP biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: >-
GMP biosynthetic process, the pathway in which IMPDH1 catalyses the committed,
rate-limiting step (IMP -> XMP -> GMP).
action: ACCEPT
reason: >-
This is the correct, appropriately specific core biological process for
IMPDH1. The enzyme makes XMP, the immediate committed precursor of GMP, in the
de novo guanine-nucleotide pathway.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "step in the de novo synthesis of guanine nucleotides"
- term:
id: GO:0016491
label: oxidoreductase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
Parent oxidoreductase activity from an InterPro mapping. IMPDH1 is an
NAD+-dependent oxidoreductase, but this is a broad ancestor of its specific
activity.
action: MODIFY
reason: >-
True but too general; the specific dehydrogenase activity is IMP dehydrogenase
activity (GO:0003938), a descendant of oxidoreductase activity. Replace with
the specific term.
proposed_replacement_terms:
- id: GO:0003938
label: IMP dehydrogenase activity
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- term:
id: GO:0046872
label: metal ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000104
qualifier: enables
review:
summary: >-
Metal-ion binding assigned by UniRule. IMPDH1 requires a monovalent cation
(K+) cofactor, with several structurally defined K+ binding sites at the
tetramer interface.
action: MODIFY
reason: >-
The generic "metal ion binding" understates the specific, functionally
important requirement for a monovalent cation (potassium). Replace with
potassium ion binding (GO:0030955), which the UniProt COFACTOR and K+ BINDING
site annotations support.
proposed_replacement_terms:
- id: GO:0030955
label: potassium ion binding
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Name=K(+)"
- term:
id: GO:0097294
label: "'de novo' XMP biosynthetic process"
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: >-
'de novo' XMP biosynthetic process is the most precise biological process for
the reaction IMPDH1 actually catalyses: IMP -> XMP is the single committed step
of de novo XMP synthesis.
action: ACCEPT
reason: >-
Directly matches the UniProt pathway annotation ("XMP biosynthesis via de novo
pathway; XMP from IMP: step 1/1") and the catalytic reaction. This is arguably
the single most accurate BP term for IMPDH1 and a core process.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "XMP biosynthesis via de novo pathway"
- term:
id: GO:0005829
label: cytosol
evidence_type: IDA
original_reference_id: GO_REF:0000052
qualifier: located_in
review:
summary: >-
Direct immunofluorescence localization (HPA) to the cytosol, the compartment
where IMPDH1 carries out de novo GMP synthesis.
action: ACCEPT
reason: >-
Experimental (IDA) cytosolic localization is the most specific and accurate
core location, consistent with the soluble cytosolic purine pathway and the
broader cytoplasm annotations.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798748
qualifier: located_in
review:
summary: >-
Extracellular localization inferred from a Reactome neutrophil-degranulation
exocytosis event (secretory granule proteins), not from a dedicated function
of IMPDH1.
action: MARK_AS_OVER_ANNOTATED
reason: >-
IMPDH1 is a soluble cytosolic enzyme. Its appearance in the extracellular
region derives from bulk proteomic detection of the neutrophil granule/secretome
and does not reflect a genuine secreted function. This is a bystander
over-annotation, not a core localization.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798751
qualifier: located_in
review:
summary: >-
Duplicate extracellular-region localization from a Reactome azurophil-granule
exocytosis event.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Same rationale as the other extracellular-region Reactome annotations: IMPDH1
is cytosolic, and its granule-lumen/extracellular assignment reflects
neutrophil-degranulation proteomics rather than a genuine secreted role.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6800434
qualifier: located_in
review:
summary: >-
Duplicate extracellular-region localization from a Reactome ficolin-rich
granule exocytosis event.
action: MARK_AS_OVER_ANNOTATED
reason: >-
As with the other Reactome degranulation-derived localizations, this reflects
bulk granule/secretome proteomics rather than a genuine extracellular function
of the cytosolic enzyme IMPDH1.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0034774
label: secretory granule lumen
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798748
qualifier: located_in
review:
summary: >-
Secretory granule lumen localization from the Reactome neutrophil-degranulation
pathway.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Cytosolic IMPDH1 is detected in neutrophil granule proteomes, but this is a
bystander/contaminant-type localization from degranulation datasets rather than
a genuine granule-lumen residence relevant to its enzymatic function.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0035578
label: azurophil granule lumen
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798751
qualifier: located_in
review:
summary: >-
Azurophil granule lumen localization from the Reactome neutrophil-degranulation
pathway.
action: MARK_AS_OVER_ANNOTATED
reason: >-
As above: derives from neutrophil granule proteomics of the cytosolic enzyme
IMPDH1 and does not reflect a core, functionally meaningful granule-lumen
localization.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:1904813
label: ficolin-1-rich granule lumen
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6800434
qualifier: located_in
review:
summary: >-
Ficolin-1-rich granule lumen localization from the Reactome
neutrophil-degranulation pathway.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Same bystander-proteomics rationale: cytosolic IMPDH1 appearing in a granule
lumen dataset does not constitute a genuine, core subcellular location for the
enzyme.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-73794
qualifier: located_in
review:
summary: >-
Cytosolic localization asserted by the Reactome IMP -> XMP reaction, the core
catalytic event of IMPDH1.
action: ACCEPT
reason: >-
Correct core localization tied directly to the catalytic reaction; consistent
with the IDA cytosol and cytoplasm annotations.
supported_by:
- reference_id: Reactome:R-HSA-73794
supporting_text: "IMP dehydrogenase 1 and 2 (IMPDH1,2) catalyze the irreversible dehydrogenation of inosine 5'-monophosphate (IMP) to form xanthosine 5'-monophosphate (XMP)"
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9678749
qualifier: located_in
review:
summary: >-
Cytosolic localization from the Reactome "IMPDH tetramers bind IMPDH inhibitors"
reaction (drug-binding context).
action: ACCEPT
reason: >-
The cytosol is the correct core compartment for IMPDH1; the annotation arises
from a drug/inhibitor-binding reaction but the localization itself is accurate
and duplicates the other cytosol annotations.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9748945
qualifier: located_in
review:
summary: >-
Cytosolic localization from the Reactome "IMPDH tetramers dehydrogenate 6TIMP
to 6TXMP" reaction (thiopurine metabolism context).
action: ACCEPT
reason: >-
Correct core localization. The reaction reflects IMPDH turnover of a thiopurine
metabolite, but the cytosolic assignment is accurate and duplicates the other
cytosol annotations.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0003676
label: nucleic acid binding
evidence_type: IDA
original_reference_id: PMID:14766016
qualifier: enables
review:
summary: >-
Direct demonstration that IMPDH (both human isoforms) binds single-stranded
nucleic acids with nanomolar affinity via its CBS subdomain, with ~100
nucleotides bound per tetramer.
action: KEEP_AS_NON_CORE
reason: >-
This is a genuine, experimentally supported moonlighting activity of IMPDH1
mediated by the regulatory CBS (Bateman) subdomain, and several RP10/LCA
disease variants alter this nucleic-acid affinity. However, the enzyme's core
function is IMP dehydrogenase catalysis; the nucleic-acid-binding role is
regulatory/moonlighting and best retained as non-core.
supported_by:
- reference_id: PMID:14766016
supporting_text: "bind single-stranded nucleic acids with nanomolar affinity via the"
- term:
id: GO:0003677
label: DNA binding
evidence_type: IDA
original_reference_id: PMID:14766016
qualifier: enables
review:
summary: >-
IMPDH was shown by immunoprecipitation to bind DNA (and RNA) in vivo, an
extension of its single-stranded nucleic-acid-binding activity.
action: KEEP_AS_NON_CORE
reason: >-
Experimentally supported (IDA) but represents the moonlighting nucleic-acid
interaction rather than a sequence-specific transcription-factor-type DNA
binding. It is a non-core, regulatory activity distinct from the enzyme's
committed metabolic role; retained as non-core per curation policy for
experimental annotations.
supported_by:
- reference_id: PMID:14766016
supporting_text: "immunoprecipitation experiments show that IMPDH binds both RNA and DNA in vivo"
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:14766016
qualifier: located_in
review:
summary: >-
Direct detection of IMPDH in the nucleus of human cells, consistent with its
nucleic-acid-binding activity.
action: KEEP_AS_NON_CORE
reason: >-
Experimentally supported nuclear pool, but the enzyme's core catalytic function
in de novo GMP synthesis is cytosolic. Nuclear localization is tied to the
moonlighting nucleic-acid-binding role and is non-core.
supported_by:
- reference_id: PMID:14766016
supporting_text: "IMPDH is found in the nucleus of human cells, as"
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:14766016
qualifier: located_in
review:
summary: >-
Direct localization of IMPDH to the cytoplasm, its principal compartment.
action: ACCEPT
reason: >-
Experimental (IDA) cytoplasmic localization corroborates the core cytosolic
residence where IMPDH1 catalyses IMP -> XMP; consistent with the IDA cytosol
and IBA/IEA cytoplasm annotations.
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
id: GO:0003938
label: IMP dehydrogenase activity
evidence_type: TAS
original_reference_id: PMID:1969416
qualifier: enables
review:
summary: >-
Traceable author statement (original cloning paper) that the two human IMPDH
cDNAs encode IMP dehydrogenase, the rate-limiting enzyme of de novo guanine
nucleotide synthesis.
action: ACCEPT
reason: >-
Core molecular function supported by the foundational cloning/characterization
paper for human IMPDH1 (type I). Duplicates GO:0003938 by other evidence codes,
which is acceptable.
supported_by:
- reference_id: PMID:1969416
supporting_text: "IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP"
core_functions:
- description: >-
NAD+-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine
5'-monophosphate (XMP), the committed and rate-limiting step of de novo
guanine-nucleotide biosynthesis, performed in the cytosol.
molecular_function:
id: GO:0003938
label: IMP dehydrogenase activity
directly_involved_in:
- id: GO:0097294
label: "'de novo' XMP biosynthetic process"
locations:
- id: GO:0005829
label: cytosol
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "Reaction=IMP + NAD(+) + H2O = XMP + NADH + H(+)"
- reference_id: PMID:1969416
supporting_text: "IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP"
- description: >-
Committed step of de novo GMP biosynthesis: by producing XMP, IMPDH1 supplies
the immediate precursor that GMP synthase aminates to GMP, thereby providing
guanine nucleotides for the cell.
molecular_function:
id: GO:0003938
label: IMP dehydrogenase activity
directly_involved_in:
- id: GO:0006177
label: GMP biosynthetic process
locations:
- id: GO:0005829
label: cytosol
supported_by:
- reference_id: file:human/IMPDH1/IMPDH1-uniprot.txt
supporting_text: "step in the de novo synthesis of guanine nucleotides"
proposed_new_terms: []
suggested_questions:
- question: >-
Is the single-stranded nucleic-acid-binding activity of the CBS subdomain a
physiologically regulated function of IMPDH1 in photoreceptors, and does its
disruption (as by RP10/LCA CBS-domain variants) cause disease independently of
catalytic activity?
- question: >-
What is the functional significance of IMPDH1 filament ("rods and rings"/
cytoophidia) assembly for guanine-nucleotide homeostasis in the retina?
suggested_experiments:
- description: >-
Separate-of-function IMPDH1 alleles that abolish catalysis while preserving
nucleic-acid binding (and vice versa) expressed in photoreceptor models, to test
whether RP10/LCA phenotypes arise from loss of catalysis, loss/alteration of
nucleic-acid binding, or a dominant-negative filament defect.
- description: >-
Cryo-EM and cellular imaging of retina-specific IMPDH1 isoforms to determine how
the extended N-terminal retinal isoforms modulate filament assembly and
GTP/GDP-dependent allosteric regulation.