id: Q9NRG9
gene_symbol: AAAS
product_type: PROTEIN
status: COMPLETE
description: 'AAAS encodes ALADIN, a WD-repeat scaffold nucleoporin of the nuclear pore complex. ALADIN is anchored at the nuclear envelope through NDC1 and contributes to normal NPC-associated nucleocytoplasmic transport, especially in tissues affected by triple-A syndrome such as adrenal, gastrointestinal, and neural systems. In mitosis, ALADIN also localizes to spindle structures and helps spatially regulate inactive Aurora A and downstream spindle factors, supporting robust spindle formation and chromosome alignment.'
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
alternative_products:
- name: 1 (AAAS-v1)
  id: Q9NRG9-1
- name: 2 (AAAS-v2)
  id: Q9NRG9-2
  sequence_note: VSP_043014
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:24315095
  title: Integrated structural analysis of the human nuclear pore complex scaffold.
  full_text_unavailable: true
  findings:
  - statement: The human NPC scaffold is a multi-nucleoporin assembly mediating nucleocytoplasmic exchange.
    supporting_text: The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells that facilitates nucleocytoplasmic exchange of macromolecules.
    full_text_unavailable: true
- id: PMID:27016207
  title: The Structure Inventory of the Nuclear Pore Complex.
  findings:
  - statement: NPCs are the principal gateway for nuclear-cytoplasmic exchange.
    supporting_text: The nuclear pore complex (NPC) is the principal gateway for molecular exchange between nucleus and cytoplasm across the nuclear envelope.
  - statement: NPCs are built from about 30 nucleoporins and positioned in nuclear-envelope openings.
    supporting_text: Analyzing the protein composition of NPCs from various eukaryotic origin reveals that they all share a set of ~30 nucleoporins (Nups).
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:28811369
  title: Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation.
  full_text_unavailable: true
  findings:
  - statement: TMEM18 interacts with nuclear pore complex components, but this does not establish a specific AAAS molecular function beyond a generic interaction.
    supporting_text: We provide evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex.
    full_text_unavailable: true
- id: PMID:27754849
  title: Identification of a novel putative interaction partner of the nucleoporin ALADIN.
  findings:
  - statement: PGRMC2 co-immunoprecipitates with ALADIN in adrenal cell models.
    supporting_text: In an attempt to identify new interaction partners of ALADIN, co-IP analyses showed that PGRMC2 precipitated with ALADIN.
  - statement: ALADIN and PGRMC2 are associated near the nuclear envelope/perinuclear ER.
    supporting_text: Taken together, our results in immunofluorescence microscopy using different ALADIN and PGRMC2 adrenal cell expression systems provide a basis for future research of how ALADIN and PGRMC2 possibly associate in a complex close to the nuclear envelope, and what the effects on steroidogenesis of this association would be.
- id: PMID:26246606
  title: The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.
  findings:
  - statement: ALADIN regulates Aurora A localization during mitotic spindle formation.
    supporting_text: In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A.
  - statement: ALADIN loss slows spindle assembly and chromosome alignment.
    supporting_text: Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment.
  - statement: ALADIN interacts with inactive Aurora A and is recruited to spindle poles after Aurora A inhibition.
    supporting_text: ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition.
- id: PMID:12730363
  title: The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome.
  full_text_unavailable: true
  findings:
  - statement: ALADIN localizes to nuclear pore complexes.
    supporting_text: ALADIN localizes to nuclear pore complexes (NPCs), large multiprotein assemblies that are the sole sites of nucleocytoplasmic transport.
    full_text_unavailable: true
  - statement: Patient mutations disrupt NPC targeting while leaving gross NPC structure intact.
    supporting_text: A variety of disease-associated missense, nonsense, and frameshift mutations failed to localize to NPCs and were found predominantly in the cytoplasm.
    full_text_unavailable: true
  - statement: The authors proposed a regulatory role in nucleocytoplasmic transport.
    supporting_text: We propose that ALADIN plays a cell type-specific role in regulating nucleocytoplasmic transport and that this function is essential for the proper maintenance andor development of certain tissues.
    full_text_unavailable: true
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  full_text_unavailable: true
  findings:
  - statement: AAAS was identified in a high-throughput membrane proteomics data set; the paper cautions that many identified proteins may only be transiently membrane-associated.
    supporting_text: The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes.
    full_text_unavailable: true
- id: PMID:21630459
  title: Proteomic characterization of the human sperm nucleus.
  full_text_unavailable: true
  findings:
  - statement: AAAS was detected in an isolated sperm nucleus proteomics data set.
    supporting_text: With this approach, 403 different proteins have been identified from the isolated sperm nuclei.
    full_text_unavailable: true
- id: Reactome:R-HSA-1176059
  title: Translocation of Influenza A virus nonstructural protein 1 (NS1A) into the nucleus
  findings: []
- id: Reactome:R-HSA-165043
  title: Rev multimer-bound HIV mRNA:Crm1:Ran:GTP complex associates with the NPC
  findings: []
- id: Reactome:R-HSA-165047
  title: Translocation of nuclear RNA transport complex to cytoplasm
  findings: []
- id: Reactome:R-HSA-170796
  title: NPC transports GCK1:GCKR from cytosol to nucleoplasm
  findings: []
- id: Reactome:R-HSA-180622
  title: Vpr binds nucleoporins
  findings: []
- id: Reactome:R-HSA-192627
  title: Viral mRNA Export
  findings: []
- id: Reactome:R-HSA-192925
  title: Export of Spliced Viral mRNA
  findings: []
- id: Reactome:R-HSA-2990880
  title: NEK6/NEK7 phosphorylates NUP98
  findings: []
- id: Reactome:R-HSA-2990882
  title: CDK1 phosphorylates NUP98
  findings: []
- id: Reactome:R-HSA-3000348
  title: RANBP2 SUMOylates SP100 with SUMO2
  findings: []
- id: Reactome:R-HSA-3000399
  title: RANBP2 SUMOylates SP100 with SUMO1
  findings: []
- id: Reactome:R-HSA-3000411
  title: RANBP2 SUMOylates PML with SUMO2
  findings: []
- id: Reactome:R-HSA-4551649
  title: RANBP2 SUMOylates RANBP2 with SUMO1
  findings: []
- id: Reactome:R-HSA-4551679
  title: RANBP2 SUMOylates RANBP2 with SUMO2
  findings: []
- id: Reactome:R-HSA-4570493
  title: RANBP2 (NUP358) SUMOylates HNRNPC with SUMO1
  findings: []
- id: Reactome:R-HSA-4615872
  title: RANBP2 SUMOylates HDAC4 with SUMO1
  findings: []
- id: Reactome:R-HSA-4615987
  title: RANBP2 SUMOylates HDAC4 with SUMO2,3
  findings: []
- id: Reactome:R-HSA-4655355
  title: RANBP2 SUMOylates CDCA8 (Borealin) and PIAS3 SUMOylates AURKB (Aurora-B)
  findings: []
- id: Reactome:R-HSA-5228508
  title: RANBP2 SUMOylates PML with SUMO1
  findings: []
- id: Reactome:R-HSA-5228523
  title: RANBP2 SUMOylates MDM2 with SUMO1
  findings: []
- id: Reactome:R-HSA-5252041
  title: NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm
  findings: []
- id: Reactome:R-HSA-5661474
  title: Defective NPC does not transport GCK1:GKRP from cytosol to nucleoplasm
  findings: []
- id: Reactome:R-HSA-6783483
  title: tRNA:XPOT:RAN:GTP translocates from the nucleus to the cytosol
  findings: []
- id: Reactome:R-HSA-75096
  title: Docking of the TAP:EJC Complex with the NPC
  findings: []
- id: Reactome:R-HSA-75097
  title: Transport of the export-competent mRNP complex through the NPC
  findings: []
- id: Reactome:R-HSA-75098
  title: mRNP complex dissociates from cytosolic face of NPC
  findings: []
- id: Reactome:R-HSA-9614367
  title: HCMV Nuclear Pore Docking
  findings: []
- id: Reactome:R-HSA-9614369
  title: Transport of HCMV DNA Into the Nucleus
  findings: []
- id: Reactome:R-HSA-9708889
  title: SARS-CoV-2 6 binds NUP98:RAE1 within NPC
  findings: []
- id: PMID:11062474
  title: Mutant WD-repeat protein in triple-A syndrome.
  full_text_unavailable: true
  findings:
  - statement: AAAS encodes ALADIN, a WD-repeat protein mutated in triple-A syndrome.
    supporting_text: The predicted product of AAAS, ALADIN (for alacrima-achalasia-adrenal insufficiency neurologic disorder), belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in triple-A syndrome.
    full_text_unavailable: true
  - statement: Expression in affected neuroendocrine and cerebral structures supports developmental and neurological relevance.
    supporting_text: The expression of the gene in both neuroendocrine and cerebral structures points to a role in the normal development of the peripheral and central nervous systems.
    full_text_unavailable: true
- id: PMID:11159947
  title: Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.
  full_text_unavailable: true
  findings:
  - statement: Loss-of-function AAAS mutations cause triple-A syndrome.
    supporting_text: In nine triple A syndrome patients eight different homozygous and compound heterozygous mutations were found in this gene, most of them leading to a truncated protein suggesting loss of function.
    full_text_unavailable: true
  - statement: AAAS is expressed in neuroendocrine and gastrointestinal structures affected in disease.
    supporting_text: RNA blotting experiments revealed marked expression in neuroendocrine and gastrointestinal structures, which are predominantly affected in triple A syndrome, supporting the hypothesis that mutations in this triple A syndrome gene (AAAS) are responsible for the disease.
    full_text_unavailable: true
- id: PMID:16022285
  title: Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS.
  full_text_unavailable: true
  findings:
  - statement: AAAS has a shorter splice variant that remains broadly expressed.
    supporting_text: RT-PCR analysis in our work revealed that AAAS-v2 and AAAS-v1 were ubiquitously detected in human multiple tissue cDNA (MTC) panels (CLONTECH).
    full_text_unavailable: true
- id: PMID:19782045
  title: The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope.
  full_text_unavailable: true
  findings:
  - statement: ALADIN is anchored in the NPC through NDC1.
    supporting_text: We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC.
    full_text_unavailable: true
  - statement: Loss of ALADIN integration into the NPC is disease-relevant.
    supporting_text: The loss of integration of ALADIN in the NPC is a main pathogenetic aspect for the development of the triple A syndrome and suggests that the interaction between ALADIN and NDC1 may be involved in the pathogenesis of the disease.
    full_text_unavailable: true
- id: file:human/AAAS/AAAS-uniprot.txt
  title: UniProtKB Q9NRG9 AAAS/ALADIN record
  findings:
  - statement: UniProt summarizes ALADIN as an NPC protein with roles in AURKA/NUMA1 localization and spindle formation.
    supporting_text: Required for the correct localization of aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 as well as a subset of AURKA targets which ensures proper spindle formation and timely chromosome alignment
  - statement: UniProt records the nuclear pore complex, spindle pole, and nuclear envelope locations.
    supporting_text: Nucleus, nuclear pore complex
- id: file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
  title: Proteostasis PN projected candidate additions for AAAS
  findings:
  - statement: PN projection suggests GO:0015031 protein transport from Nuclear proteostasis | Protein transport, but this is a broad class-level projection and is not added as a new AAAS annotation in this conservative review.
    supporting_text: "AAAS\t\tGO:0015031\tprotein transport\tnew_to_goa\tok_for_propagation_to_go\tnuclear_proteostasis.yaml\tNuclear proteostasis|Protein transport\tNuclear proteostasis|Protein transport|Nuclear pore complex"
- id: file:human/AAAS/AAAS-deep-research-falcon.md
  title: Falcon deep research report for human AAAS
  findings:
  - statement: Falcon deep research summarizes AAAS/ALADIN as an NPC/nuclear-envelope scaffold whose localization is NDC1-dependent.
    supporting_text: ALADIN localizes to the **NPC/nuclear envelope**; proper NE/NPC targeting is **NDC1-dependent**.
  - statement: Falcon deep research treats ALADIN as a scaffold/selective transport regulator rather than an enzyme or small-molecule transporter.
    supporting_text: 'Best-supported current interpretation: ALADIN is a **scaffold/selective transport regulator at the NPC**, not an enzyme or transporter with a defined small-molecule substrate.'
existing_annotations:
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: AAAS/ALADIN is a nuclear pore complex nucleoporin. Disease-associated ALADIN variants lose NPC targeting, and NDC1 anchoring is required for ALADIN localization at the nuclear envelope.
    action: ACCEPT
    reason: The nuclear pore annotation is a central, well-supported cellular component for AAAS. The PN nuclear-pore projection also agrees with existing GOA, but it adds no new term beyond this already captured location.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - &id001
      reference_id: PMID:12730363
      supporting_text: ALADIN localizes to nuclear pore complexes (NPCs), large multiprotein assemblies that are the sole sites of nucleocytoplasmic transport.
      reference_section_type: ABSTRACT
    - &id002
      reference_id: PMID:19782045
      supporting_text: We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006913
    label: nucleocytoplasmic transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: ALADIN is an NPC-associated protein implicated in normal nucleocytoplasmic transport rather than gross NPC structure. Existing IBA/NAS/IDA transport rows are consistent with the disease-mutant mislocalization evidence and NPC biology.
    action: ACCEPT
    reason: Nucleocytoplasmic transport is more informative and better scoped for AAAS than the PN-projected broad parent protein transport. I retain this existing transport term and do not add GO:0015031 protein transport from the PN projection.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - &id003
      reference_id: PMID:12730363
      supporting_text: We propose that ALADIN plays a cell type-specific role in regulating nucleocytoplasmic transport and that this function is essential for the proper maintenance andor development of certain tissues.
      reference_section_type: ABSTRACT
    - &id004
      reference_id: PMID:27016207
      supporting_text: The nuclear pore complex (NPC) is the principal gateway for molecular exchange between nucleus and cytoplasm across the nuclear envelope.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ALADIN localizes to mitotic spindle structures, including the spindle pole, in the AURKA/spindle study.
    action: ACCEPT
    reason: The mitotic localization is experimentally supported and functionally tied to ALADIN-dependent spatial regulation of Aurora A. This is a genuine AAAS role, distinct from but compatible with its NPC identity.
    supported_by:
    - &id005
      reference_id: PMID:26246606
      supporting_text: Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment.
      reference_section_type: ABSTRACT
    - &id006
      reference_id: PMID:26246606
      supporting_text: ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear envelope/nuclear membrane localization is consistent with ALADIN being an NPC nucleoporin anchored through NDC1.
    action: ACCEPT
    reason: This cellular component is well supported by ALADIN-specific localization and anchoring evidence. For the HPA-derived nuclear membrane row, the term is less specific than nuclear pore but still consistent with the NPC location at the nuclear envelope.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: part_of
  review:
    summary: AAAS/ALADIN is a nuclear pore complex nucleoporin. Disease-associated ALADIN variants lose NPC targeting, and NDC1 anchoring is required for ALADIN localization at the nuclear envelope.
    action: ACCEPT
    reason: The nuclear pore annotation is a central, well-supported cellular component for AAAS. The PN nuclear-pore projection also agrees with existing GOA, but it adds no new term beyond this already captured location.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IDA
  original_reference_id: PMID:24315095
  qualifier: located_in
  review:
    summary: The original structural NPC-scaffold source has only abstract text available locally, but independent ALADIN-specific evidence supports nuclear-envelope/NPC localization.
    action: ACCEPT
    reason: Retain the nuclear envelope annotation because ALADIN is directly shown to be anchored in the nuclear envelope via NDC1. The unavailable original full text limits direct assessment of the 2013 structural study details, so the review also relies on ALADIN-specific localization evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:24315095
      supporting_text: The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells that facilitates nucleocytoplasmic exchange of macromolecules.
      reference_section_type: ABSTRACT
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: NAS
  original_reference_id: PMID:24315095
  qualifier: part_of
  review:
    summary: AAAS/ALADIN is a nuclear pore complex nucleoporin. Disease-associated ALADIN variants lose NPC targeting, and NDC1 anchoring is required for ALADIN localization at the nuclear envelope.
    action: ACCEPT
    reason: The nuclear pore annotation is a central, well-supported cellular component for AAAS. The PN nuclear-pore projection also agrees with existing GOA, but it adds no new term beyond this already captured location.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0006913
    label: nucleocytoplasmic transport
  evidence_type: NAS
  original_reference_id: PMID:27016207
  qualifier: involved_in
  review:
    summary: ALADIN is an NPC-associated protein implicated in normal nucleocytoplasmic transport rather than gross NPC structure. Existing IBA/NAS/IDA transport rows are consistent with the disease-mutant mislocalization evidence and NPC biology.
    action: ACCEPT
    reason: Nucleocytoplasmic transport is more informative and better scoped for AAAS than the PN-projected broad parent protein transport. I retain this existing transport term and do not add GO:0015031 protein transport from the PN projection.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: The HPA-derived nucleoplasm signal is plausible for an NPC-associated protein but is less specific than nuclear pore/nuclear envelope localization.
    action: KEEP_AS_NON_CORE
    reason: AAAS should primarily be represented as a nuclear pore/nuclear envelope component. Nucleoplasm localization may reflect immunofluorescence signal or cell-state context and is not the best descriptor of the core site of action.
    supported_by:
    - reference_id: PMID:12730363
      supporting_text: ALADIN localizes to nuclear pore complexes (NPCs), large multiprotein assemblies that are the sole sites of nucleocytoplasmic transport.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Nuclear envelope/nuclear membrane localization is consistent with ALADIN being an NPC nucleoporin anchored through NDC1.
    action: ACCEPT
    reason: This cellular component is well supported by ALADIN-specific localization and anchoring evidence. For the HPA-derived nuclear membrane row, the term is less specific than nuclear pore but still consistent with the NPC location at the nuclear envelope.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28811369
  qualifier: enables
  review:
    summary: This protein binding row comes from a TMEM18 study that reports interaction with NPC components. It does not define a specific AAAS molecular function.
    action: REMOVE
    reason: GO:0005515 protein binding is too generic for curation and the source is primarily about TMEM18 biology. The finding may identify AAAS as an NPC component/interactor, but that context is already captured by nuclear pore and nucleocytoplasmic transport annotations.
    supported_by:
    - reference_id: PMID:28811369
      supporting_text: We provide evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27754849
  qualifier: enables
  review:
    summary: The PGRMC2 interaction with ALADIN is experimentally supported, but protein binding is uninformative as a GO molecular-function annotation.
    action: REMOVE
    reason: The interaction should be retained as biological evidence in the notes/reference findings, not as the generic GO:0005515 term. No more specific AAAS molecular-function term is supported strongly enough from this interaction alone.
    supported_by:
    - reference_id: PMID:27754849
      supporting_text: In an attempt to identify new interaction partners of ALADIN, co-IP analyses showed that PGRMC2 precipitated with ALADIN.
      reference_section_type: DISCUSSION
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IDA
  original_reference_id: PMID:27754849
  qualifier: located_in
  review:
    summary: ALADIN is observed at the nuclear envelope/perinuclear region in adrenal-cell interaction experiments with PGRMC2.
    action: ACCEPT
    reason: This is consistent with the core NPC/nuclear-envelope localization of AAAS. The PGRMC2 paper supports nuclear-envelope localization and an interaction context, but it should not be inflated into a specific transport or steroidogenesis GO process for AAAS.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:27754849
      supporting_text: We detected that PGRMC2 co-localises with ALADIN and with different FG-repeat NUPs [stained with anti-NPC proteins (mAb414)] to the nuclear envelope and the perinuclear ER.
      reference_section_type: RESULTS
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IDA
  original_reference_id: PMID:26246606
  qualifier: located_in
  review:
    summary: ALADIN localizes to mitotic spindle structures, including the spindle pole, in the AURKA/spindle study.
    action: ACCEPT
    reason: The mitotic localization is experimentally supported and functionally tied to ALADIN-dependent spatial regulation of Aurora A. This is a genuine AAAS role, distinct from but compatible with its NPC identity.
    supported_by:
    - *id005
    - *id006
- term:
    id: GO:0001578
    label: microtubule bundle formation
  evidence_type: IMP
  original_reference_id: PMID:26246606
  qualifier: involved_in
  review:
    summary: ALADIN depletion produces shorter, less robust spindles and affects spindle microtubule organization.
    action: KEEP_AS_NON_CORE
    reason: The phenotype supports a role in spindle organization, but microtubule bundle formation is a less direct and less informative description than mitotic spindle assembly/AURKA localization. Keep the row as non-core supporting phenotype rather than the main process term.
    supported_by:
    - *id005
    - *id006
- term:
    id: GO:0072686
    label: mitotic spindle
  evidence_type: IDA
  original_reference_id: PMID:26246606
  qualifier: located_in
  review:
    summary: ALADIN localizes to mitotic spindle structures, including the mitotic spindle, in the AURKA/spindle study.
    action: ACCEPT
    reason: The mitotic localization is experimentally supported and functionally tied to ALADIN-dependent spatial regulation of Aurora A. This is a genuine AAAS role, distinct from but compatible with its NPC identity.
    supported_by:
    - *id005
    - *id006
- term:
    id: GO:0090307
    label: mitotic spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:26246606
  qualifier: involved_in
  review:
    summary: ALADIN is required for robust mitotic spindle formation and timely chromosome alignment through spatial regulation of Aurora A and associated spindle factors.
    action: ACCEPT
    reason: This is directly supported by depletion experiments in human and Drosophila cells and by phenotypes in triple-A patient fibroblasts. It should be retained as a well-supported AAAS biological process.
    supported_by:
    - *id005
    - *id006
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IDA
  original_reference_id: PMID:12730363
  qualifier: part_of
  review:
    summary: AAAS/ALADIN is a nuclear pore complex nucleoporin. Disease-associated ALADIN variants lose NPC targeting, and NDC1 anchoring is required for ALADIN localization at the nuclear envelope.
    action: ACCEPT
    reason: The nuclear pore annotation is a central, well-supported cellular component for AAAS. The PN nuclear-pore projection also agrees with existing GOA, but it adds no new term beyond this already captured location.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: AAAS was detected in a high-throughput membrane proteomics study, but generic membrane localization is much less informative than nuclear envelope/nuclear pore.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is not strictly false because the NPC is embedded in the nuclear envelope, but this HDA row loses the important nuclear-pore context and the source study includes many proteins predicted to be transiently associated with membranes.
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:21630459
  qualifier: located_in
  review:
    summary: AAAS was detected in a sperm nucleus proteomics data set, but generic nucleus localization is broader than the established nuclear pore/nuclear envelope site.
    action: MARK_AS_OVER_ANNOTATED
    reason: The nucleus term is broadly compatible with an NPC protein but over-generalizes the curated AAAS localization. Nuclear pore and nuclear envelope should be preferred for functional interpretation.
    supported_by:
    - reference_id: PMID:21630459
      supporting_text: With this approach, 403 different proteins have been identified from the isolated sperm nuclei.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1176059
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-165043
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-165047
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-170796
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-180622
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192627
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192925
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2990880
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2990882
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000348
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000399
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000411
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4551649
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4551679
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4570493
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4615872
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4615987
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4655355
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5228508
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5228523
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5252041
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5661474
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6783483
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75096
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75097
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75098
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9614367
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9614369
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9708889
  qualifier: located_in
  review:
    summary: AAAS is correctly placed at the nuclear envelope/NPC, but the Reactome source event should be treated as location context only for this nuclear envelope row.
    action: ACCEPT
    reason: The Reactome row should be interpreted only as cellular-component support for AAAS/ALADIN being part of the nuclear-envelope/NPC machinery. The specific Reactome events range across viral transport, mRNA/tRNA transport, SUMOylation, and disease pathways and should not be used to infer those pathway processes for AAAS without separate gene-level evidence.
    additional_reference_ids:
    - PMID:19782045
    supported_by:
    - reference_id: PMID:19782045
      supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
      reference_section_type: ABSTRACT
- term:
    id: GO:0006913
    label: nucleocytoplasmic transport
  evidence_type: IDA
  original_reference_id: PMID:12730363
  qualifier: acts_upstream_of_or_within
  review:
    summary: ALADIN is an NPC-associated protein implicated in normal nucleocytoplasmic transport rather than gross NPC structure. Existing IBA/NAS/IDA transport rows are consistent with the disease-mutant mislocalization evidence and NPC biology.
    action: ACCEPT
    reason: Nucleocytoplasmic transport is more informative and better scoped for AAAS than the PN-projected broad parent protein transport. I retain this existing transport term and do not add GO:0015031 protein transport from the PN projection.
    additional_reference_ids:
    - PMID:19782045
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id003
    - *id004
- term:
    id: GO:0046822
    label: regulation of nucleocytoplasmic transport
  evidence_type: NAS
  original_reference_id: PMID:12730363
  qualifier: involved_in
  review:
    summary: The original ALADIN disease-mutant study explicitly proposed a regulatory role in nucleocytoplasmic transport.
    action: ACCEPT
    reason: This term is a conservative way to capture ALADIN as an NPC-associated regulator/support factor rather than a transport receptor or cargo-specific transporter. It is preferable to adding broad protein transport from the PN projection.
    additional_reference_ids:
    - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv
    supported_by:
    - *id003
    - *id004
core_functions:
- description: ALADIN is a scaffold nucleoporin of the nuclear pore complex at the nuclear envelope. Its NDC1-dependent NPC anchoring supports normal NPC-associated nucleocytoplasmic transport; disease-associated variants commonly fail to target to NPCs, linking loss of NPC integration to triple-A syndrome biology.
  directly_involved_in:
  - id: GO:0006913
    label: nucleocytoplasmic transport
  - id: GO:0046822
    label: regulation of nucleocytoplasmic transport
  locations:
  - id: GO:0005635
    label: nuclear envelope
  in_complex:
    id: GO:0005643
    label: nuclear pore
  supported_by:
  - reference_id: PMID:12730363
    supporting_text: A variety of disease-associated missense, nonsense, and frameshift mutations failed to localize to NPCs and were found predominantly in the cytoplasm.
    reference_section_type: ABSTRACT
  - reference_id: PMID:19782045
    supporting_text: Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated.
    reference_section_type: ABSTRACT
  - reference_id: file:human/AAAS/AAAS-deep-research-falcon.md
    supporting_text: 'Best-supported current interpretation: ALADIN is a **scaffold/selective transport regulator at the NPC**, not an enzyme or transporter with a defined small-molecule substrate.'
- description: During mitosis, ALADIN acts as a spatial regulator of Aurora A localization and associated spindle factors, supporting robust mitotic spindle formation and timely chromosome alignment.
  directly_involved_in:
  - id: GO:0090307
    label: mitotic spindle assembly
  locations:
  - id: GO:0072686
    label: mitotic spindle
  - id: GO:0000922
    label: spindle pole
  supported_by:
  - *id005
  - *id006
  - reference_id: file:human/AAAS/AAAS-deep-research-falcon.md
    supporting_text: 'Best-supported current interpretation: ALADIN is a **scaffold/selective transport regulator at the NPC**, not an enzyme or transporter with a defined small-molecule substrate.'
proposed_new_terms: []
suggested_questions:
- question: Should AAAS be annotated to a more specific nuclear protein import/export term only if future gene-level evidence identifies affected protein cargos, rather than adding the broad PN-projected GO:0015031 protein transport?
  experts:
  - Cronshaw JM
  - Matunis MJ
  - Kind B
  - Huebner A
- question: Is the ALADIN-PGRMC2 association functionally upstream of adrenal steroidogenesis in vivo, or should it remain an interaction note without a GO process annotation?
  experts:
  - Juehlen R
  - Koehler K
  - Huebner A
suggested_experiments:
- hypothesis: ALADIN loss selectively alters nuclear import or export of stress-response or DNA-repair proteins in adrenal and neural cell types.
  description: Perform quantitative nuclear/cytoplasmic proteomics or live import/export reporter assays in AAAS-null and rescue human adrenal/neural cell models, with cargo-level validation for candidate proteins.
  experiment_type: nucleocytoplasmic transport assay
- hypothesis: The ALADIN-PGRMC2 interaction has a specific steroidogenic consequence rather than representing proximity at the perinuclear ER/NPC.
  description: Compare steroidogenic enzyme activity, PGRMC2 localization, and CYP-dependent steroid output in AAAS knockout, NDC1-anchoring-defective rescue, and wild-type rescue adrenocortical cells.
  experiment_type: functional rescue and steroidogenesis assay