SMOX

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (PAN-GO) inference placing SMOX in the cytoplasm. Consistent with the experimentally determined localization of isoform 1 (IDA, PMID:18422650) and UniProt, which report SMOX in the cytoplasm/cytosol. A more specific experimentally supported location (cytosol, GO:0005829) is also annotated; keep this general cytoplasm location as non-core. Reason: Correct cellular component but general; the specific cytosol location (GO:0005829, IDA) better captures where the soluble enzyme acts.
GO:0046592 polyamine oxidase activity	IBA GO_REF:0000033	MODIFY	Summary: Phylogenetic inference of the general family activity (polyamine oxidase). SMOX's specific, experimentally demonstrated activity is spermine oxidase activity (GO:0052901), a child of polyamine oxidase activity. The general term is not wrong but the specific term is available and directly supported, so it should be used instead. Reason: A more specific and experimentally supported term (spermine oxidase activity, GO:0052901) exists and is the enzyme's characterized activity. Proposed replacements: spermine oxidase activity
GO:0046208 spermine catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that SMOX participates in spermine catabolism. This is the core biological process for SMOX, which oxidatively degrades spermine to spermidine. Directly supported by experimental data (isoform 1 IDA, PMID:18422650) and the UniProt spermine-degradation pathway. Reason: Correctly captures the enzyme's core catabolic role; consistent with experimental annotations.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Electronic mapping from the UniProt Subcellular Location vocabulary (Nucleus). Consistent with experimental evidence that SMOX isoforms localize to the nucleus (isoform 1 IDA, PMID:18422650), where spermine oxidation generates H2O2 near DNA. Reason: Nuclear localization is experimentally supported (PMID:18422650) and biologically important for the DNA-damage phenotype.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic mapping from the UniProt Subcellular Location vocabulary (Cytoplasm). Consistent with experimental evidence (isoform 1 IDA, PMID:18422650) and the annotated cytosol location. Keep as a general, non-core location alongside the more specific cytosol term. Reason: Correct but general; the specific cytosol location (GO:0005829) is the core location for this soluble enzyme.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro-to-GO mapping from the amine oxidase domain (IPR002937) to the broad parent term oxidoreductase activity. While SMOX is an oxidoreductase, this term is far more general than the specific, experimentally established spermine oxidase activity (GO:0052901) that is also annotated. Reason: Uninformatively general parent of the characterized spermine oxidase activity; the specific term is available and directly supported.
GO:0046592 polyamine oxidase activity	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning electronic annotation to the general family activity. As with the IBA polyamine oxidase annotation, the specific characterized activity spermine oxidase activity (GO:0052901) is available and directly supported, so the more specific term should be used. Reason: A more specific, experimentally supported term (GO:0052901) exists and is the enzyme's characterized activity. Proposed replacements: spermine oxidase activity
GO:0052901 spermine oxidase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation derived from the RHEA:25804 / EC 1.5.3.16 mapping to spermine oxidase activity. This is the correct, specific molecular function of SMOX and is independently supported by multiple experimental annotations (EXP: PMID:11454677, PMID:12141946, PMID:12398765; IDA: PMID:12477380). Reason: Correct specific molecular function, matching the UniProt catalytic activity and the experimentally established reaction.
GO:0052901 spermine oxidase activity	IDA PMID:12477380 Genomic identification and biochemical characterization of t...	ACCEPT	Summary: Direct-assay annotation of spermine oxidase activity. The paper's abstract foregrounds the N1-acetylpolyamine oxidase (PAO/PAOX) that prefers N1-acetylspermine, explicitly contrasting it with the spermine oxidase (SMO) which prefers spermine over N1-acetylspermine; the curator (FlyBase) had the full text and attributed the spermine oxidase activity to SMOX. This is the enzyme's core, experimentally verified molecular function. Reason: Core molecular function; experimental (IDA) annotation consistent with all other biochemical characterizations of SMOX.
GO:0052901 spermine oxidase activity	IDA Q9NWM0-1 PMID:18422650 Nuclear localization of human spermine oxidase isoforms - po...	ACCEPT	Summary: Direct-assay annotation showing isoform 1 (SMO/PAOh1) oxidizes spermine; the paper also characterizes the SMO5/isoform 6 splice variant with substrate specificities and affinities comparable to those of SMO/PAOh1. Core molecular function of SMOX; the isoform tag marks what was assayed, not an isoform-restricted activity. Reason: Core molecular function directly demonstrated for the displayed isoform.
GO:0006596 polyamine biosynthetic process	TAS Reactome:R-HSA-351200	MARK AS OVER ANNOTATED	Summary: TAS annotation propagated from the Reactome Interconversion of polyamines pathway, which groups both biosynthetic aminopropyltransferase steps and catabolic oxidase steps. SMOX is a catabolic enzyme that degrades spermine to spermidine; it does not biosynthesize polyamines. Its role in the interconversion pathway recycles spermine to spermidine (a catabolic / back-conversion event), so polyamine biosynthetic process mis-frames the enzyme's direction and is an over-annotation arising from the mixed-content Reactome pathway. Reason: SMOX is catabolic (spermine to spermidine + H2O2); biosynthesis is the wrong process direction. The correct catabolic processes are separately annotated.
GO:0006805 xenobiotic metabolic process	TAS Reactome:R-HSA-141334	MARK AS OVER ANNOTATED	Summary: TAS annotation from the Reactome PAOs oxidise polyamines to amines reaction, whose summary notes that PAOs act on endogenous polyamines as well as some xenobiotics. SMOX's characterized, physiological substrate is endogenous spermine; there is no experimental evidence that SMOX metabolizes xenobiotics. This is a family-level generalization that does not reflect the specific biology of SMOX. Reason: No SMOX-specific evidence for xenobiotic metabolism; the enzyme acts on the endogenous polyamine spermine.
GO:0046208 spermine catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (ARBA / UniPathway UPA00211 spermine degradation) to spermine catabolic process. This is the core biological process of SMOX and matches the UniProt PATHWAY assignment and the experimental IDA annotation (PMID:18422650). Reason: Correct core catabolic process, consistent with experimental evidence.
GO:0052901 spermine oxidase activity	TAS Reactome:R-HSA-141341	ACCEPT	Summary: TAS annotation from the Reactome reaction SMOX-3 oxidises SPN to SPM (spermine oxidase flavoenzyme catalysing oxidation of spermine to spermidine). Correct specific molecular function, corroborating the experimental spermine oxidase activity annotations. Reason: Correct specific molecular function, consistent with experimental evidence.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence localization to the nucleoplasm. Consistent with the experimentally demonstrated nuclear localization of SMOX isoforms (PMID:18422650), where nuclear spermine oxidation generates H2O2 near DNA. A more specific sub-nuclear compartment than the core nucleus location. Reason: Supported sub-nuclear localization; retained as a specific, non-core location alongside the core nucleus annotation.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence localization to the cytosol. SMOX is a soluble flavoenzyme lacking membrane- or organelle-targeting signals, and the cytosol is where much of its spermine oxidation occurs. This is a core location for the enzyme's activity. Reason: Core cytosolic location for a soluble amine oxidase, supported by direct immunofluorescence.
GO:0031965 nuclear membrane	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: HPA immunofluorescence signal at the nuclear membrane. SMOX is a soluble protein with no known transmembrane domain or membrane anchor; a nuclear-membrane assignment likely reflects perinuclear / nuclear-envelope staining rather than integral nuclear-membrane residence. It is at best a minor, non-core localization compared with the well-supported cytosol and nucleoplasm/nucleus locations. Reason: SMOX has no membrane-targeting features; the nuclear-membrane signal is likely perinuclear and is not a core location of the soluble enzyme.
GO:0052901 spermine oxidase activity	EXP PMID:11454677 Cloning and characterization of a human polyamine oxidase th...	ACCEPT	Summary: Original cloning and biochemical characterization of human SMOX (PAOh1). The cDNA product has PAO activity that is inhibited by MDL 72,527, a specific inhibitor of mammalian PAO, but not by monoamine- or diamine-oxidase inhibitors, establishing the FAD-dependent polyamine / spermine oxidase activity that defines SMOX (UniProt cites this reference for EC 1.5.3.16). Core molecular function. Reason: Core, experimentally established molecular function from the founding characterization of the enzyme.
GO:0052901 spermine oxidase activity	EXP PMID:12141946 Identification and characterization of a novel flavin-contai...	ACCEPT	Summary: Biochemical identification of SMOX as a novel flavin-containing spermine oxidase of mammalian cell origin that strongly favoured spermine over N1-acetylspermine and failed to act on N1-acetylspermidine, spermidine or the preferred PAO substrate N1,N12-diacetylspermine, directly defining spermine oxidase activity. Core molecular function. Reason: Core molecular function; direct biochemical demonstration of spermine oxidase activity and its substrate preference.
GO:0052901 spermine oxidase activity	EXP PMID:12398765 Cloning and characterization of multiple human polyamine oxi...	ACCEPT	Summary: Cloning and characterization of multiple human SMOX splice variants coding for isoenzymes with distinct biochemical characteristics but efficient oxidation of polyamines (spermine). UniProt cites this reference for the EC 1.5.3.16 catalytic activity and the spermine-degradation pathway. Core molecular function. Reason: Core molecular function; experimentally established across the isoform set.
GO:0005829 cytosol	TAS Reactome:R-HSA-141341	ACCEPT	Summary: TAS cytosol location from the Reactome SMOX oxidation reaction. Consistent with the direct HPA immunofluorescence cytosol annotation. Core location for the soluble enzyme. Reason: Corroborates the core cytosolic location of the enzyme.
GO:0006598 polyamine catabolic process	IDA PMID:12477380 Genomic identification and biochemical characterization of t...	KEEP AS NON CORE	Summary: Direct-assay annotation placing SMOX in polyamine catabolism. The paper characterizes the polyamine back-conversion pathway (SSAT acetylation then oxidation by PAO) and contrasts it with SMO, which directly oxidizes spermine. Involvement in polyamine catabolism is correct; the more specific spermine catabolic process (GO:0046208) is separately annotated and better captures the exact substrate. Reason: Correct but more general than the specific spermine catabolic process; kept as a valid, broader catabolic annotation.
GO:0005634 nucleus	IDA Q9NWM0-1 PMID:18422650 Nuclear localization of human spermine oxidase isoforms - po...	ACCEPT	Summary: Direct demonstration that overexpressed SMO/PAOh1 (isoform 1) shows significant localization in the nucleus by confocal microscopy, with increased spermine oxidation in the nucleus producing H2O2 close to DNA. Core, functionally important nuclear localization. Reason: Experimentally demonstrated core nuclear localization with direct functional (DNA-damage) relevance.
GO:0005737 cytoplasm	IDA Q9NWM0-1 PMID:18422650 Nuclear localization of human spermine oxidase isoforms - po...	KEEP AS NON CORE	Summary: Direct-assay cytoplasmic localization of isoform 1. Consistent with the soluble nature of the enzyme and the cytosol annotations. Keep as a valid general location; the specific cytosol term is treated as core. Reason: Correct but general cytoplasmic location; specific cytosol (GO:0005829) is the core location term.
GO:0046208 spermine catabolic process	IDA Q9NWM0-1 PMID:18422650 Nuclear localization of human spermine oxidase isoforms - po...	ACCEPT	Summary: Direct-assay annotation that isoform 1 participates in spermine catabolism, based on increased spermine oxidation in the nucleus with accompanying alterations in individual nuclear polyamine concentrations. This is the core biological process of SMOX. Reason: Core catabolic process, experimentally demonstrated for the displayed isoform.

Gene Description

Existing Annotations Review

Core Functions

FAD-dependent oxidation of the free polyamine spermine to spermidine, with production of 3-aminopropanal and hydrogen peroxide (spermine oxidase activity; EC 1.5.3.16), the direct back-conversion step of polyamine catabolism.

Binding of the FAD cofactor required for the amine-oxidase catalytic cycle; SMOX binds one FAD per subunit as a member of the flavin monoamine oxidase family.

References

📚 Additional Documentation

Notes

📄 View Raw YAML