PAOX is the human peroxisomal N(1)-acetylpolyamine oxidase (also called polyamine oxidase, PAO/APAO; EC 1.5.3.13), an FAD-dependent flavoenzyme of the flavin monoamine oxidase family. It catalyzes the oxidative arm of polyamine back-conversion: acting on N(1)-acetylated polyamines produced by spermidine/spermine N1-acetyltransferase (SAT1), it oxidizes N(1)-acetylspermine to spermidine and N(1)-acetylspermidine to putrescine, in each case releasing 3-acetamidopropanal and hydrogen peroxide. Its substrate preference is N(1)-acetylspermine = N(1)-acetylspermidine > N(1),N(12)-diacetylspermine, and it does not oxidize free spermidine; its requirement for the acetylated substrate distinguishes it from spermine oxidase (SMOX), which oxidizes free spermine. By interconverting higher and lower polyamines, PAOX helps set intracellular polyamine concentrations. The protein carries a C-terminal PTS1 microbody targeting signal and localizes to the peroxisomal matrix, with a cytosolic (pre-import) pool. It is widely expressed and induced by polyamine analogs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) cytoplasm annotation. PAOX is a peroxisomal matrix enzyme bearing a C-terminal PTS1 microbody targeting signal; UniProt lists both Peroxisome and Cytoplasm. The cytoplasmic pool most plausibly reflects the newly-synthesized, pre-import protein. This is true but non-core; the functional compartment is the peroxisome. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0046592 polyamine oxidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) polyamine oxidase activity, the parent molecular function. Consistent with the experimentally demonstrated FAD-dependent oxidation of N(1)-acetylated polyamines. Correct; retained as a core MF (the more specific term GO:0052903 is also annotated experimentally). Supporting Evidence: PMID:12477380 rapidly oxidized N1-acetylspermine to |
| GO:0046203 spermidine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) spermidine catabolic process. PAOX oxidizes N(1)-acetylspermidine (a spermidine derivative) and, via the back-conversion pathway, participates in spermidine turnover. Correct and core to the back-conversion arm of polyamine catabolism. Supporting Evidence: PMID:16354669 one of the key enzymes in |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation mapped from the UniProt "Cytoplasm" subcellular location keyword. As with the IBA cytoplasm annotation, this reflects a pre-import/cytosolic pool; the functional compartment is the peroxisomal matrix. True but non-core. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from the UniProt "Peroxisome" subcellular location. Strongly supported: PAOX carries a C-terminal PTS1 microbody targeting signal (residues 509-511) and is imported as a PEX5 cargo. Core cellular component. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Microbody targeting signal |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic (ARBA/InterPro) oxidoreductase activity. Correct in essence (PAOX is an FAD-dependent oxidoreductase) but far too general; the specific, experimentally supported activity is N(1)-acetylpolyamine oxidase activity. Proposed replacements: N(1)-acetylpolyamine oxidase activity Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Reaction=N(1)-acetylspermine + O2 + H2O = 3-acetamidopropanal + |
| GO:0052903 N(1)-acetylpolyamine oxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (EC/Rhea) mapping of the exact reaction PAOX catalyzes. Matches the experimental EXP annotation from PMID:12477380 (same term). This is the core molecular function. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Reaction=N(1)-acetylspermidine + O2 + H2O = 3-acetamidopropanal + |
| GO:0005782 peroxisomal matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transfer (Ensembl Compara) peroxisomal matrix localization, consistent with the PTS1 signal and Reactome's placement of PAOX activity in the peroxisomal matrix. Core compartment (more specific than GO:0005777). Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Microbody targeting signal |
| GO:0006598 polyamine catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transfer polyamine catabolic process. This is the overarching biological process for PAOX in the back-conversion pathway; matches the experimental IDA evidence. Core. Supporting Evidence: PMID:16354669 one of the key enzymes in |
| GO:0010509 intracellular polyamine homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-transfer intracellular polyamine homeostasis. Biologically true (overexpression shifts spermine/spermidine pools), but this is a high-level systemic outcome rather than the direct molecular/pathway role. Kept as non-core. Supporting Evidence: PMID:12477380 intracellular spermine pools decreased by approx. 30%, whereas |
| GO:0046203 spermidine catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transfer spermidine catabolic process, duplicating the IBA and IDA annotations to the same term. Core back-conversion process. Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:0046208 spermine catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transfer spermine catabolic process. PAOX contributes to spermine turnover by oxidizing N(1)-acetylspermine (the SAT1-acetylated spermine) to spermidine, the committed step of spermine back-conversion. Core. Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:0046592 polyamine oxidase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-transfer polyamine oxidase activity, duplicating the IBA and IDA MF annotations. Correct core molecular function (parent of GO:0052903). Supporting Evidence: PMID:12477380 rapidly oxidized N1-acetylspermine to |
| GO:0008215 spermine metabolic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: UniPathway-derived spermine metabolic process, matching UniProt's PATHWAY "spermine metabolism". Correct but a general parent process; the specific, directional roles are captured by the spermine/spermidine catabolic process terms. Kept as non-core. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Amine and polyamine metabolism; spermine metabolism. |
| GO:0052903 N(1)-acetylpolyamine oxidase activity | EXP PMID:12477380 Genomic identification and biochemical characterization of t... | ACCEPT | Summary: Experimental (EXP) N(1)-acetylpolyamine oxidase activity from Vujcic et al. 2003. Lysates of human PAOX-transfected HEK-293 cells rapidly oxidized N1-acetylspermine to spermidine, with the diagnostic substrate ranking (N1-acetylspermine = N1-acetylspermidine > N1,N12-diacetylspermine >> spermine; spermidine not a substrate). This is the defining core molecular function of PAOX. Supporting Evidence: PMID:12477380 a preference ranking of N1-acetylspermine= N1-acetylspermidine> N1,N12-diacetylspermine>>spermine; spermidine was not acted upon |
| GO:0005782 peroxisomal matrix | TAS Reactome:R-HSA-141348 | ACCEPT | Summary: Reactome TAS peroxisomal matrix, from the reaction "PAO:FAD oxidises NASPM to PTCN" (N1-acetylspermidine to putrescine). Consistent with the PTS1 signal and UniProt peroxisome localization. Core compartment. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Microbody targeting signal |
| GO:0005782 peroxisomal matrix | TAS Reactome:R-HSA-141351 | ACCEPT | Summary: Reactome TAS peroxisomal matrix, from the reaction "PAOX:FAD oxidises NASPN to SPM" (N1-acetylspermine to spermidine). Same well-supported peroxisomal localization. Core compartment (duplicate of the other Reactome/Ensembl matrix annotations). Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Microbody targeting signal |
| GO:0005782 peroxisomal matrix | TAS Reactome:R-HSA-9033235 | ACCEPT | Summary: Reactome TAS peroxisomal matrix, associated with PAOX being imported as a PTS1 cargo into the peroxisomal matrix (PEX5-mediated translocation). Consistent with the functional localization. Core compartment. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Microbody targeting signal |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033235 | KEEP AS NON CORE | Summary: Reactome TAS cytosol, reflecting the pre-import (cytosolic) state of PAOX before PEX5-mediated translocation into the peroxisome. Represents a transit pool rather than the functional site. Non-core. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9033236 | KEEP AS NON CORE | Summary: Reactome TAS cytosol, from the step where the PEX5:PAOX (PTS1 cargo) complex binds the peroxisomal docking/translocation module. Again a pre-import transit state; non-core relative to the peroxisomal matrix. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0009446 putrescine biosynthetic process | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | KEEP AS NON CORE | Summary: Experimental (IDA) putrescine biosynthetic process from Järvinen et al. 2006. Putrescine is a reaction product of PAOX-catalyzed oxidation of N(1)-acetylspermidine, so this "biosynthetic" framing describes product formation within the catabolic back-conversion pathway rather than a dedicated biosynthetic role of PAOX. Retained as experimental evidence but marked non-core (the core is the catabolic oxidase activity). Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:1901307 positive regulation of spermidine biosynthetic process | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | KEEP AS NON CORE | Summary: Experimental (IDA) positive regulation of spermidine biosynthesis. PAOX generates spermidine as a product of N(1)-acetylspermine oxidation, and its overexpression raises spermidine pools 2-4 fold; this term captures that downstream effect on spermidine levels rather than a distinct regulatory mechanism. Kept as non-core; the direct function is the oxidase activity. Supporting Evidence: PMID:12477380 intracellular spermine pools decreased by approx. 30%, whereas |
| GO:0009447 putrescine catabolic process | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | KEEP AS NON CORE | Summary: Experimental (IDA) putrescine catabolic process. In the context of PAOX, putrescine is a product of back-conversion rather than a substrate; the broader amine-oxidase activity may act on some derivatives, but PAOX is not a canonical putrescine-degrading enzyme. Retained as experimental evidence but marked non-core. Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:0046203 spermidine catabolic process | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | ACCEPT | Summary: Experimental (IDA) spermidine catabolic process. PAOX oxidizes N(1)-acetylspermidine (the acetylated spermidine derivative), the committed catabolic step of the back-conversion arm. Core biological process. Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:0046208 spermine catabolic process | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | ACCEPT | Summary: Experimental (IDA) spermine catabolic process. PAOX oxidizes N(1)-acetylspermine (SAT1-acetylated spermine) to spermidine, executing the committed oxidative step of spermine back-conversion. Core biological process. Supporting Evidence: PMID:16354669 the catabolism of polyamines spermidine and spermine. The natural substrates for |
| GO:0046592 polyamine oxidase activity | IDA PMID:16354669 Guide molecule-driven stereospecific degradation of alpha-me... | ACCEPT | Summary: Experimental (IDA) polyamine oxidase activity from Järvinen et al. 2006, an enzymology study confirming FAD-dependent oxidation of N1-acetylspermidine, N1-acetylspermine and N1,N12-diacetylspermine. Core molecular function (parent of the more specific GO:0052903). Supporting Evidence: PMID:16354669 is one of the key enzymes in |
| GO:0050660 flavin adenine dinucleotide binding | IEA file:human/PAOX/PAOX-uniprot.txt | NEW | Summary: Not present in the current GOA seed, but PAOX is an FAD-dependent flavoenzyme that binds one FAD per subunit (UniProt COFACTOR, with multiple FAD-binding residues annotated by similarity to mouse Paox). FAD binding is a core molecular function required for its oxidase activity and is proposed as a NEW annotation. Supporting Evidence: file:human/PAOX/PAOX-uniprot.txt Note=Binds 1 FAD per subunit. |
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