Antizyme inhibitor 2 (AZIN2, also ADC/ODC-paralogue) is a catalytically dead member of the Orn/Lys/Arg decarboxylase class-II family. Despite early reports of ornithine or arginine decarboxylase activity, it has neither. Its function is regulatory: AZIN2 binds ornithine-decarboxylase antizymes (OAZ1/2/3) and sequesters them, thereby relieving antizyme-mediated inhibition and degradation of ornithine decarboxylase (ODC), positively regulating polyamine biosynthesis. AZIN2 is expressed in brain and testis, associates with the ER-Golgi/secretory and vesicular compartments, and has roles in vesicle trafficking and spermatogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009446 putrescine biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: putrescine biosynthetic process: process annotation for AZIN2. Reason: Valid but non-core / secondary. |
| GO:0004586 ornithine decarboxylase activity | IBA NOT GO_REF:0000033 | ACCEPT | Summary: NOT: AZIN2 does not have ornithine decarboxylase activity. It is a catalytically dead paralog of ODC in the Orn/Lys/Arg decarboxylase family. Reason: Correct, important negation. Retain. Supporting Evidence: file:human/AZIN2/AZIN2-uniprot.txt but it was later found that the mouse ortholog does not possess either of them |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0042177 negative regulation of protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of protein catabolic process: by sequestering antizyme, AZIN2 prevents antizyme-mediated proteasomal degradation of ODC. Reason: Core process tied to the antizyme-inhibitor function. Retain. |
| GO:1902269 positive regulation of polyamine transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: positive regulation of polyamine transmembrane transport: a core biological process for AZIN2. Reason: Core process consistent with AZIN2's established function. |
| GO:0042978 ornithine decarboxylase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ornithine decarboxylase activator activity: AZIN2's real molecular function - it binds antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC. Reason: Core molecular function (a regulatory, non-catalytic activity). Retain. |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | REMOVE | Summary: Generic 'catalytic activity' (IEA) from the decarboxylase-family signature. AZIN2 has no demonstrated catalytic activity; its function (antizyme inhibition / ODC activation) is regulatory, not catalytic. Reason: Electronic over-propagation onto a catalytically dead paralog. Remove. Supporting Evidence: file:human/AZIN2/AZIN2-uniprot.txt but it was later found that the mouse ortholog does not possess either of them |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: nucleus: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: cytoplasm: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: endoplasmic reticulum-Golgi intermediate compartment: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Golgi apparatus: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0006596 polyamine biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: polyamine biosynthetic process: process annotation for AZIN2. Reason: Valid but non-core / secondary. |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: membrane: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0016831 carboxy-lyase activity | IEA GO_REF:0000117 | REMOVE | Summary: Positive 'carboxy-lyase activity' (IEA), the parent of decarboxylase activity, from the family signature. Reason: Electronic over-propagation of decarboxylase activity onto AZIN2, which lacks it (curated NOT|ODC). Remove. |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: axon: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: dendrite: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytoplasmic vesicle: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: perikaryon: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183). Reason: High-throughput protein binding is uninformative about molecular function (curation guideline). Over-annotation. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: mitochondrion: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005801 cis-Golgi network | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cis-Golgi network: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: endoplasmic reticulum-Golgi intermediate compartment membrane: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0042978 ornithine decarboxylase activator activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ornithine decarboxylase activator activity: AZIN2's real molecular function - it binds antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC. Reason: Core molecular function (a regulatory, non-catalytic activity). Retain. |
| GO:1902269 positive regulation of polyamine transmembrane transport | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of polyamine transmembrane transport: a core biological process for AZIN2. Reason: Core process consistent with AZIN2's established function. |
| GO:0097055 agmatine biosynthetic process | TAS Reactome:R-HSA-351143 | REMOVE | Summary: Agmatine biosynthetic process (TAS, Reactome) - the product of arginine decarboxylase, an activity AZIN2 lacks. Reason: Process annotation dependent on the defunct arginine-decarboxylase activity (UniProt CAUTION). Remove. Supporting Evidence: file:human/AZIN2/AZIN2-uniprot.txt but it was later found that the mouse ortholog does not possess either of them |
| GO:0008792 arginine decarboxylase activity | TAS Reactome:R-HSA-350598 | REMOVE | Summary: Legacy positive arginine decarboxylase activity (TAS, Reactome). The CAUTION notes AZIN2 was initially reported to have ODC/ADC activity but the ortholog has neither. Reason: Superseded enzymatic claim, contradicted by the CAUTION. Remove. Supporting Evidence: file:human/AZIN2/AZIN2-uniprot.txt but it was later found that the mouse ortholog does not possess either of them |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: cytosol: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0005634 nucleus | IDA PMID:19832840 Brain neurons express ornithine decarboxylase-activating ant... | ACCEPT | Summary: nucleus: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0030424 axon | IDA PMID:19832840 Brain neurons express ornithine decarboxylase-activating ant... | KEEP AS NON CORE | Summary: axon: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0030425 dendrite | IDA PMID:19832840 Brain neurons express ornithine decarboxylase-activating ant... | KEEP AS NON CORE | Summary: dendrite: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0031410 cytoplasmic vesicle | IDA PMID:19832840 Brain neurons express ornithine decarboxylase-activating ant... | KEEP AS NON CORE | Summary: cytoplasmic vesicle: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0043204 perikaryon | IDA PMID:19832840 Brain neurons express ornithine decarboxylase-activating ant... | KEEP AS NON CORE | Summary: perikaryon: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005801 cis-Golgi network | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cis-Golgi network: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005802 trans-Golgi network | IDA PMID:20188728 Ornithine decarboxylase antizyme inhibitor 2 regulates intra... | KEEP AS NON CORE | Summary: trans-Golgi network: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0030133 transport vesicle | IMP PMID:20188728 Ornithine decarboxylase antizyme inhibitor 2 regulates intra... | KEEP AS NON CORE | Summary: transport vesicle: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0031410 cytoplasmic vesicle | IDA PMID:20188728 Ornithine decarboxylase antizyme inhibitor 2 regulates intra... | KEEP AS NON CORE | Summary: cytoplasmic vesicle: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: endoplasmic reticulum-Golgi intermediate compartment membrane: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20188728 Ornithine decarboxylase antizyme inhibitor 2 regulates intra... | KEEP AS NON CORE | Summary: perinuclear region of cytoplasm: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0098629 trans-Golgi network membrane organization | IMP PMID:20188728 Ornithine decarboxylase antizyme inhibitor 2 regulates intra... | KEEP AS NON CORE | Summary: trans-Golgi network membrane organization: process annotation for AZIN2. Reason: Valid but non-core / secondary. |
| GO:0005515 protein binding | IPI PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym... | KEEP AS NON CORE | Summary: Specific protein interaction (PMID:17900240) consistent with AZIN2's scaffold/adapter role. Reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term is itself uninformative. |
| GO:0042177 negative regulation of protein catabolic process | IDA PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym... | ACCEPT | Summary: Negative regulation of protein catabolic process: by sequestering antizyme, AZIN2 prevents antizyme-mediated proteasomal degradation of ODC. Reason: Core process tied to the antizyme-inhibitor function. Retain. |
| GO:0042978 ornithine decarboxylase activator activity | ISS GO_REF:0000024 | ACCEPT | Summary: Ornithine decarboxylase activator activity: AZIN2's real molecular function - it binds antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC. Reason: Core molecular function (a regulatory, non-catalytic activity). Retain. |
| GO:0042978 ornithine decarboxylase activator activity | IDA PMID:17900240 Human ornithine decarboxylase paralogue (ODCp) is an antizym... | ACCEPT | Summary: Ornithine decarboxylase activator activity: AZIN2's real molecular function - it binds antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC. Reason: Core molecular function (a regulatory, non-catalytic activity). Retain. |
| GO:0043085 positive regulation of catalytic activity | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of catalytic activity: AZIN2 increases ODC activity by relieving antizyme inhibition. Reason: Core regulatory process consistent with the activator function. Retain. |
| GO:1902269 positive regulation of polyamine transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: positive regulation of polyamine transmembrane transport: a core biological process for AZIN2. Reason: Core process consistent with AZIN2's established function. |
| GO:0005634 nucleus | IDA PMID:19718454 Expression of antizyme inhibitor 2 in mast cells and role of... | ACCEPT | Summary: nucleus: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:1990005 granular vesicle | IDA PMID:19718454 Expression of antizyme inhibitor 2 in mast cells and role of... | KEEP AS NON CORE | Summary: granular vesicle: a secondary/broad localization for AZIN2. Reason: Plausible but non-core (broad term or context-specific). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-350598 | ACCEPT | Summary: cytosol: a core subcellular location for AZIN2. Reason: Correct core localization. |
| GO:0007283 spermatogenesis | NAS PMID:11587527 Expression of a novel human ornithine decarboxylase-like pro... | ACCEPT | Summary: spermatogenesis: a core biological process for AZIN2. Reason: Core process consistent with AZIN2's established function. |
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Download this section (compressed HTML)Q: Do the AZIN1 and AZIN2 paralogs have distinct antizyme preferences or subcellular sites of ODC activation?
Experiment: Assay purified AZIN2 for ODC/ADC activity (negative control) and measure ODC stabilization in cells co-expressing AZIN2 and antizyme.
Hypothesis: AZIN2 activates ODC purely by antizyme sequestration, with no intrinsic decarboxylase activity.
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