ODC1 is ornithine decarboxylase (EC 4.1.1.17), the pyridoxal 5'-phosphate (PLP)-dependent lyase that catalyzes the first and rate-limiting step of polyamine biosynthesis: decarboxylation of L-ornithine to putrescine plus CO2. Putrescine is the precursor of the higher polyamines spermidine and spermine, which are essential for cell proliferation, growth and differentiation. The enzyme is an obligate homodimer whose two active sites are built from residues of both subunits (Lys69 covalently binds the PLP cofactor; Cys360 acts as the proton donor), so only the dimer is catalytically active. ODC is among the most tightly regulated enzymes in eukaryotes: it has an exceptionally short half-life and its degradation is triggered by ornithine decarboxylase antizymes (OAZ1/2/3), which bind ODC monomers, prevent productive dimerization and target ODC for ubiquitin-independent destruction by the 26S proteasome; antizyme inhibitors (AZIN1/AZIN2) counteract this. ODC acts in the cytosol (and nucleus). In humans, gain-of-function C-terminal truncating variants that escape nonsense-mediated decay cause Bachmann-Bupp syndrome, and ODC/polyamine metabolism is a well-established cancer drug target (irreversibly inhibited by alpha-difluoromethylornithine/eflornithine).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009446 putrescine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the rate-limiting step of putrescine biosynthesis. This is a core biological process for ODC1 and is well supported by the enzyme's catalytic activity and pathway placement. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) is_active_in cytoplasm. ODC is a cytosolic enzyme; cytoplasm/cytosol is its correct localization. The more precise cytosol (GO:0005829) is also annotated by Reactome. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0004586 ornithine decarboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation of the defining catalytic activity of ODC1. This is the core molecular function and is directly supported by experimental structural/kinetic characterization of human ODC. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Reaction=L-ornithine + H(+) = putrescine + CO2 |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IEA) annotation of the generic root-level catalytic activity. This is correct but far too general given that the specific activity (ornithine decarboxylase, GO:0004586) is experimentally established. Replace with the specific molecular function. Proposed replacements: ornithine decarboxylase activity Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Reaction=L-ornithine + H(+) = putrescine + CO2 |
| GO:0004586 ornithine decarboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA, combined-method / EC 4.1.1.17 mapping) annotation of the core catalytic activity. Correct and redundant with the experimental GO:0004586 annotations. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt EC=4.1.1.17 |
| GO:0006595 polyamine metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation to the broad parent process. Correct but general; the specific putrescine/polyamine biosynthetic process better captures ODC's role. Kept as a non-core, correct-but-general grouping term. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt which is the precursor for the polyamines, spermidine and spermine |
| GO:0006596 polyamine biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IEA) annotation to polyamine biosynthetic process. Correct; ODC catalyzes the committed first step of polyamine biosynthesis. Slightly more general than the specific putrescine biosynthetic process but accurate. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Catalyzes the first and rate-limiting step of polyamine biosynthesis |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale binary interactome screen (partner Q92993 = KAT5). Uninformative as a molecular function; not removed per policy for IPI protein-binding, but flagged as over-annotated. ODC's biologically meaningful binding (antizyme OAZ and antizyme inhibitor AZIN) is captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a large-scale AP-MS interactome study (partner Q9UMX2 = OAZ3, an antizyme). The uninformative "protein binding" term is marked over-annotated; the underlying OAZ interaction is biologically real and captured by the antizyme-binding function in core_functions. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from an interactome-perturbation screen (partner Q9H8Y8 = GORASP2). Uninformative molecular-function term; marked over-annotated per policy (IPI protein binding not removed). |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a variant-effect interactome study (partner Q9UMX2 = OAZ3). Uninformative term; over-annotated. The OAZ (antizyme) interaction itself is meaningful and captured in core_functions. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from the HuRI reference binary interactome (partners include Q92993 = KAT5, Q9H8Y8 = GORASP2, Q9UMX2-2 = OAZ3). Uninformative MF term; over-annotated per policy. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a cell-specific AP-MS interactome study (partner Q9UMX2 = OAZ3). Uninformative term; over-annotated. OAZ binding is real and captured separately. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-projected (IEA) cytoplasm localization from mouse ortholog (P00860). Consistent with the established cytosolic localization of ODC. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0009446 putrescine biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-projected (IEA) putrescine biosynthetic process from mouse ortholog. Core biological process; correct. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt converts ornithine into putrescine |
| GO:0042176 regulation of protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl-projected (IEA) "regulation of protein catabolic process". This reflects the fact that ODC is itself a substrate of antizyme-directed ubiquitin-independent proteasomal degradation and that its C-terminal degradation elements are the target of that pathway. As a process ascribed to ODC it reads as ODC regulating catabolism, which over-interprets the biology (ODC is the regulated target, not the regulator). Not a core function; retained as a non-core, indirect involvement. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-projected (IEA) homodimerization activity. Well supported: ODC is an obligate homodimer and only the dimer is catalytically active, with active sites built from residues of both subunits. Core to the enzyme's function. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Homodimer. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers |
| GO:0006595 polyamine metabolic process | TAS Reactome:R-HSA-351202 | KEEP AS NON CORE | Summary: Reactome TAS annotation to the broad polyamine metabolic process ("Metabolism of polyamines"). Correct but general; kept as a non-core grouping term, subsumed by the specific putrescine/polyamine biosynthetic process annotations. Supporting Evidence: Reactome:R-HSA-351202 Polyamine levels are tightly regulated at the level of the enzyme ornithine decarboxylase (ODC) |
| GO:0042978 ornithine decarboxylase activator activity | EXP PMID:10623504 Crystal structure of human ornithine decarboxylase at 2.1 A ... | MARK AS OVER ANNOTATED | Summary: This term means "binds to and increases ornithine decarboxylase activity", i.e. it describes an activator OF ODC (the role of antizyme inhibitors AZIN1/AZIN2), not the decarboxylase itself. ODC1 is the enzyme, not its activator, so this is a wrong-direction over-annotation. The cited reference (PMID:10623504) is the human ODC crystal structure and concerns antizyme-binding/structure, not an activator activity of ODC. Per policy an experimental (EXP) annotation is not removed; marked as over-annotated. The genuine molecular function is ornithine decarboxylase activity (GO:0004586). Supporting Evidence: PMID:10623504 Ornithine decarboxylase (ODC, EC 4.1.1.17) performs the first step in polyamine biosynthesis, the decarboxylation of ornithine to putrescine. |
| GO:0004586 ornithine decarboxylase activity | EXP PMID:17407445 A structural insight into the inhibition of human and Leishm... | ACCEPT | Summary: Experimental (EXP) annotation of the core ornithine decarboxylase activity, supported by structural and kinetic characterization of human ODC (KM 0.08 mM for L-ornithine; EC 4.1.1.17 assigned from this study). Core molecular function. Supporting Evidence: PMID:17407445 the first committed enzyme in the polyamine biosynthesis pathway |
| GO:0005829 cytosol | TAS Reactome:R-HSA-350567 | ACCEPT | Summary: Reactome TAS cytosol localization (antizyme-binding reaction context). ODC is cytosolic; correct core localization. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-350578 | ACCEPT | Summary: Reactome TAS cytosol localization (NQO1-ODC interaction context). Redundant with other cytosol annotations; correct core localization. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-353125 | ACCEPT | Summary: Reactome TAS cytosol localization (proteasomal degradation-of-ODC context). Redundant with other cytosol annotations; correct. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-70692 | ACCEPT | Summary: Reactome TAS cytosol localization tied directly to the ornithine => putrescine + CO2 reaction. Correct core localization for the enzymatic activity. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9955574 | ACCEPT | Summary: Reactome TAS cytosol localization (ODC dimerization context). Consistent with cytosolic dimeric holoenzyme; correct. Supporting Evidence: Reactome:R-HSA-9955574 Cytosolic pyridoxal phosphate-conjugated ornithine decarboxylase 1 (PXLP-K69-ODC1) monomers dimerize to form catalytically active ODC |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ISS transfer (from mouse ortholog P00860) of cytoplasm localization. Consistent with established cytosolic localization; correct. Supporting Evidence: Reactome:R-HSA-70692 L-ornithine is converted into putrescine by cytosolic ornithine decarboxylase (ODC). |
| GO:0004586 ornithine decarboxylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ISS transfer (from mouse ortholog P00860) of the core ornithine decarboxylase activity. Correct and redundant with the experimental GO:0004586 annotations. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Reaction=L-ornithine + H(+) = putrescine + CO2 |
| GO:0004586 ornithine decarboxylase activity | IDA PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym... | ACCEPT | Summary: Direct-assay (IDA) annotation of ornithine decarboxylase activity. The cited study measured ODC activity and ODC degradation to characterize the ODC/antizyme/antizyme-inhibitor system, using human ODC as the enzyme. Core molecular function. Supporting Evidence: PMID:17900240 ODC (ornithine decarboxylase), the rate-limiting enzyme in polyamine biosynthesis |
| GO:0009446 putrescine biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ISS transfer (from mouse ortholog) of putrescine biosynthetic process. Core biological process; correct. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt converts ornithine into putrescine |
| GO:0042176 regulation of protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator ISS transfer of "regulation of protein catabolic process". As with the IEA version, this reflects ODC being the target of antizyme-directed proteasomal degradation (its C-terminus carries degradation determinants) rather than ODC actively regulating catabolism. Not a core function; kept as non-core indirect involvement. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ISS transfer (from mouse ortholog) of homodimerization activity. Strongly supported: ODC functions only as a homodimer with shared active sites. Core to activity. Supporting Evidence: file:human/ODC1/ODC1-uniprot.txt Homodimer. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers |
| GO:0009615 response to virus | IEP PMID:16548883 Transcriptomic and proteomic analyses of rhabdomyosarcoma ce... | KEEP AS NON CORE | Summary: IEP annotation from a transcriptomic/proteomic study reporting that ODC1 protein and mRNA are down-regulated upon enterovirus 71 infection of rhabdomyosarcoma cells. This is a differential-expression observation in one viral context, not evidence of a dedicated antiviral function of ODC1. Kept as a non-core annotation. Supporting Evidence: PMID:16548883 Western blot analyses of APOB, CLU, DCAMKL1 and ODC1 proteins correlated protein and transcript levels. |
| GO:0004586 ornithine decarboxylase activity | TAS PMID:2317811 Expression of human chromosome 2 ornithine decarboxylase gen... | ACCEPT | Summary: TAS annotation of ornithine decarboxylase activity. The cited study demonstrated that the human chromosome-2 ODC gene encodes functional ODC by expressing it in ODC-deficient CHO cells, restoring 70-400-fold ODC activity. Core molecular function; correct. Supporting Evidence: PMID:2317811 the ODC gene from human chromosome 2 encodes functional ODC protein |
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Download this section (compressed HTML)Q: Beyond the cytosol, under what conditions does ODC1 localize to or act in the nucleus, and is any nuclear pool functionally distinct?
Experiment: Structure-guided mutagenesis of the ODC1 C-terminal degradation elements to dissect how Bachmann-Bupp gain-of-function truncations increase enzyme stability/activity and putrescine output, paired with polyamine metabolomics in patient-derived cells.
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