AZIN2

# yaml-language-server: $schema=../../../src/ai_gene_review/schema/gene_review.yaml
id: Q96A70
gene_symbol: AZIN2
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: '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.'
alternative_products:
- name: '1'
  id: Q96A70-1
- name: '2'
  id: Q96A70-2
  sequence_note: VSP_003756
- name: '3'
  id: Q96A70-3
  sequence_note: VSP_003757, VSP_003758
- name: '4'
  id: Q96A70-4
  sequence_note: VSP_003755, VSP_003757, VSP_003758
- name: '6'
  id: Q96A70-5
  sequence_note: VSP_003754, VSP_003757, VSP_003758
existing_annotations:
- term:
    id: GO:0009446
    label: putrescine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'putrescine biosynthetic process: process annotation for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0004586
    label: ornithine decarboxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  negated: true
  review:
    summary: 'NOT: AZIN2 does not have ornithine decarboxylase activity. It is a catalytically dead paralog
      of ODC in the Orn/Lys/Arg decarboxylase family.'
    action: ACCEPT
    reason: Correct, important negation. Retain.
    supported_by:
    - reference_id: file:human/AZIN2/AZIN2-uniprot.txt
      supporting_text: but it was later found that the mouse ortholog does not possess either of them
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: 'cytoplasm: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0042177
    label: negative regulation of protein catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'Negative regulation of protein catabolic process: by sequestering antizyme, AZIN2 prevents
      antizyme-mediated proteasomal degradation of ODC.'
    action: ACCEPT
    reason: Core process tied to the antizyme-inhibitor function. Retain.
- term:
    id: GO:1902269
    label: positive regulation of polyamine transmembrane transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'positive regulation of polyamine transmembrane transport: a core biological process for
      AZIN2.'
    action: ACCEPT
    reason: Core process consistent with AZIN2's established function.
- term:
    id: GO:0042978
    label: ornithine decarboxylase activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: 'Ornithine decarboxylase activator activity: AZIN2''s real molecular function - it binds
      antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC.'
    action: ACCEPT
    reason: Core molecular function (a regulatory, non-catalytic activity). Retain.
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: REMOVE
    reason: Electronic over-propagation onto a catalytically dead paralog. Remove.
    supported_by:
    - reference_id: file:human/AZIN2/AZIN2-uniprot.txt
      supporting_text: but it was later found that the mouse ortholog does not possess either of them
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'nucleus: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cytoplasm: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'endoplasmic reticulum-Golgi intermediate compartment: a secondary/broad localization for
      AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: 'Golgi apparatus: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0006596
    label: polyamine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: 'polyamine biosynthetic process: process annotation for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'membrane: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0016831
    label: carboxy-lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: Positive 'carboxy-lyase activity' (IEA), the parent of decarboxylase activity, from the family
      signature.
    action: REMOVE
    reason: Electronic over-propagation of decarboxylase activity onto AZIN2, which lacks it (curated
      NOT|ODC). Remove.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'axon: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'dendrite: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'cytoplasmic vesicle: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0043204
    label: perikaryon
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'perikaryon: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: 'perinuclear region of cytoplasm: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:25416956).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic 'protein binding' from a high-throughput interactome screen (PMID:32296183).
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput protein binding is uninformative about molecular function (curation guideline).
      Over-annotation.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'mitochondrion: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005801
    label: cis-Golgi network
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'cis-Golgi network: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0033116
    label: endoplasmic reticulum-Golgi intermediate compartment membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: 'endoplasmic reticulum-Golgi intermediate compartment membrane: a secondary/broad localization
      for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0042978
    label: ornithine decarboxylase activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: 'Ornithine decarboxylase activator activity: AZIN2''s real molecular function - it binds
      antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC.'
    action: ACCEPT
    reason: Core molecular function (a regulatory, non-catalytic activity). Retain.
- term:
    id: GO:1902269
    label: positive regulation of polyamine transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: 'positive regulation of polyamine transmembrane transport: a core biological process for
      AZIN2.'
    action: ACCEPT
    reason: Core process consistent with AZIN2's established function.
- term:
    id: GO:0097055
    label: agmatine biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-351143
  qualifier: involved_in
  review:
    summary: Agmatine biosynthetic process (TAS, Reactome) - the product of arginine decarboxylase, an
      activity AZIN2 lacks.
    action: REMOVE
    reason: Process annotation dependent on the defunct arginine-decarboxylase activity (UniProt CAUTION).
      Remove.
    supported_by:
    - reference_id: file:human/AZIN2/AZIN2-uniprot.txt
      supporting_text: but it was later found that the mouse ortholog does not possess either of them
- term:
    id: GO:0008792
    label: arginine decarboxylase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-350598
  qualifier: enables
  review:
    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.
    action: REMOVE
    reason: Superseded enzymatic claim, contradicted by the CAUTION. Remove.
    supported_by:
    - reference_id: file:human/AZIN2/AZIN2-uniprot.txt
      supporting_text: but it was later found that the mouse ortholog does not possess either of them
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19832840
  qualifier: located_in
  review:
    summary: 'nucleus: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IDA
  original_reference_id: PMID:19832840
  qualifier: located_in
  review:
    summary: 'axon: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:19832840
  qualifier: located_in
  review:
    summary: 'dendrite: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IDA
  original_reference_id: PMID:19832840
  qualifier: located_in
  review:
    summary: 'cytoplasmic vesicle: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0043204
    label: perikaryon
  evidence_type: IDA
  original_reference_id: PMID:19832840
  qualifier: located_in
  review:
    summary: 'perikaryon: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005801
    label: cis-Golgi network
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'cis-Golgi network: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:20188728
  qualifier: located_in
  review:
    summary: 'trans-Golgi network: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0030133
    label: transport vesicle
  evidence_type: IMP
  original_reference_id: PMID:20188728
  qualifier: located_in
  review:
    summary: 'transport vesicle: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IDA
  original_reference_id: PMID:20188728
  qualifier: located_in
  review:
    summary: 'cytoplasmic vesicle: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0033116
    label: endoplasmic reticulum-Golgi intermediate compartment membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: 'endoplasmic reticulum-Golgi intermediate compartment membrane: a secondary/broad localization
      for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20188728
  qualifier: located_in
  review:
    summary: 'perinuclear region of cytoplasm: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0098629
    label: trans-Golgi network membrane organization
  evidence_type: IMP
  original_reference_id: PMID:20188728
  qualifier: involved_in
  review:
    summary: 'trans-Golgi network membrane organization: process annotation for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Valid but non-core / secondary.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17900240
  qualifier: enables
  review:
    summary: Specific protein interaction (PMID:17900240) consistent with AZIN2's scaffold/adapter role.
    action: KEEP_AS_NON_CORE
    reason: Real interaction kept as non-core supporting evidence; the generic 'protein binding' term
      is itself uninformative.
- term:
    id: GO:0042177
    label: negative regulation of protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:17900240
  qualifier: involved_in
  review:
    summary: 'Negative regulation of protein catabolic process: by sequestering antizyme, AZIN2 prevents
      antizyme-mediated proteasomal degradation of ODC.'
    action: ACCEPT
    reason: Core process tied to the antizyme-inhibitor function. Retain.
- term:
    id: GO:0042978
    label: ornithine decarboxylase activator activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: 'Ornithine decarboxylase activator activity: AZIN2''s real molecular function - it binds
      antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC.'
    action: ACCEPT
    reason: Core molecular function (a regulatory, non-catalytic activity). Retain.
- term:
    id: GO:0042978
    label: ornithine decarboxylase activator activity
  evidence_type: IDA
  original_reference_id: PMID:17900240
  qualifier: enables
  review:
    summary: 'Ornithine decarboxylase activator activity: AZIN2''s real molecular function - it binds
      antizymes (OAZ1/2/3) and sequesters them, releasing/stabilizing active ODC.'
    action: ACCEPT
    reason: Core molecular function (a regulatory, non-catalytic activity). Retain.
- term:
    id: GO:0043085
    label: positive regulation of catalytic activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'Positive regulation of catalytic activity: AZIN2 increases ODC activity by relieving antizyme
      inhibition.'
    action: ACCEPT
    reason: Core regulatory process consistent with the activator function. Retain.
- term:
    id: GO:1902269
    label: positive regulation of polyamine transmembrane transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: 'positive regulation of polyamine transmembrane transport: a core biological process for
      AZIN2.'
    action: ACCEPT
    reason: Core process consistent with AZIN2's established function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19718454
  qualifier: located_in
  review:
    summary: 'nucleus: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:1990005
    label: granular vesicle
  evidence_type: IDA
  original_reference_id: PMID:19718454
  qualifier: located_in
  review:
    summary: 'granular vesicle: a secondary/broad localization for AZIN2.'
    action: KEEP_AS_NON_CORE
    reason: Plausible but non-core (broad term or context-specific).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-350598
  qualifier: located_in
  review:
    summary: 'cytosol: a core subcellular location for AZIN2.'
    action: ACCEPT
    reason: Correct core localization.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: NAS
  original_reference_id: PMID:11587527
  qualifier: involved_in
  review:
    summary: 'spermatogenesis: a core biological process for AZIN2.'
    action: ACCEPT
    reason: Core process consistent with AZIN2's established function.
references:
- id: GO_REF:0000002
  title: GO annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified annotations to orthologs by curator judgment
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: GO annotation based on curation of immunofluorescence data (HPA)
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Automatic GO annotation from UniProtKB-KW mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/AZIN2/AZIN2-uniprot.txt
  title: UniProt entry for AZIN2
  findings: []
- id: PMID:11587527
  title: Expression of a novel human ornithine decarboxylase-like protein in the central nervous system
    and testes.
  findings: []
- id: PMID:17900240
  title: Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase.
  findings: []
- id: PMID:19718454
  title: Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators
    of serotonin secretion.
  findings: []
- id: PMID:19832840
  title: Brain neurons express ornithine decarboxylase-activating antizyme inhibitor 2 with accumulation
    in Alzheimer's disease.
  findings: []
- id: PMID:20188728
  title: Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: Reactome:R-HSA-350598
  title: Reactome pathway
  findings: []
- id: Reactome:R-HSA-351143
  title: Reactome pathway
  findings: []
aliases:
- ADC
- AZIN2
- Antizyme inhibitor 2
- ODC-paralogue
core_functions:
- description: 'Catalytically dead ODC paralog that acts as an antizyme inhibitor: it binds and sequesters
    ornithine-decarboxylase antizymes, stabilizing and activating ODC to promote polyamine biosynthesis.'
  molecular_function:
    id: GO:0042978
    label: ornithine decarboxylase activator activity
  directly_involved_in:
  - id: GO:0042177
    label: negative regulation of protein catabolic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/AZIN2/AZIN2-uniprot.txt
    supporting_text: but it was later found that the mouse ortholog does not possess either of them
suggested_questions:
- question: Do the AZIN1 and AZIN2 paralogs have distinct antizyme preferences or subcellular sites of
    ODC activation?
suggested_experiments:
- hypothesis: AZIN2 activates ODC purely by antizyme sequestration, with no intrinsic decarboxylase activity.
  description: Assay purified AZIN2 for ODC/ADC activity (negative control) and measure ODC stabilization
    in cells co-expressing AZIN2 and antizyme.