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 | MARK AS OVER ANNOTATED | Summary: Ensembl ortholog projection of a mouse Azin2 mitochondrion annotation that rests on a crude mitochondrial/membrane fraction and was later contradicted by the same group's localization study. Reason: ORGANELLES check (2026-10-24), as a synthesis row. GO_REF:0000107 projects mouse Azin2 (Q8BVM4); QuickGO shows its positive mitochondrion row is an MGI IDA on PMID:16916800, whose only location datum is that the transfected protein was mainly in the "mitochondrial/membrane fraction", a crude pellet that cannot separate mitochondria from ER, Golgi or vesicle membranes. The same group then localized AZIN2 in transfected cells to the ERGIC and cis-Golgi network (PMID:19449338), and UniProt curators gave mouse Azin2 a NOT located_in mitochondrion IDA on that paper; the projection carried the positive row but not the negation. The human UniProt record lists nucleus, cytoplasm, ERGIC, Golgi, vesicle and granule locations but not mitochondrion, and no cached study places human AZIN2 in mitochondria. The organelle claim is not supported, so no sub-compartment is considered. Marked as over-annotation rather than removed because the projection faithfully copies a real (if superseded) experimental row. Supporting Evidence: PMID:16916800 ODCp protein was mainly localized in the mitochondrial/membrane fraction PMID:19449338 AZIN2 was located in the ER-Golgi intermediate compartment (ERGIC) and in the cis-Golgi network |
| 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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