Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Integrated structural analysis of the human nuclear pore complex scaffold.
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The human NPC scaffold is a multi-nucleoporin assembly mediating nucleocytoplasmic exchange.
"The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells that facilitates nucleocytoplasmic exchange of macromolecules."
The Structure Inventory of the Nuclear Pore Complex.
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NPCs are the principal gateway for nuclear-cytoplasmic exchange.
"The nuclear pore complex (NPC) is the principal gateway for molecular exchange between nucleus and cytoplasm across the nuclear envelope."
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NPCs are built from about 30 nucleoporins and positioned in nuclear-envelope openings.
"Analyzing the protein composition of NPCs from various eukaryotic origin reveals that they all share a set of ~30 nucleoporins (Nups)."
Gene Ontology annotation based on curation of immunofluorescence data
Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation.
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TMEM18 interacts with nuclear pore complex components, but this does not establish a specific AAAS molecular function beyond a generic interaction.
"We provide evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex."
Identification of a novel putative interaction partner of the nucleoporin ALADIN.
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PGRMC2 co-immunoprecipitates with ALADIN in adrenal cell models.
"In an attempt to identify new interaction partners of ALADIN, co-IP analyses showed that PGRMC2 precipitated with ALADIN."
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ALADIN and PGRMC2 are associated near the nuclear envelope/perinuclear ER.
"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."
The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.
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ALADIN regulates Aurora A localization during mitotic spindle formation.
"In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A."
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ALADIN loss slows spindle assembly and chromosome alignment.
"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."
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ALADIN interacts with inactive Aurora A and is recruited to spindle poles after Aurora A inhibition.
"ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition."
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome.
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ALADIN localizes to nuclear pore complexes.
"ALADIN localizes to nuclear pore complexes (NPCs), large multiprotein assemblies that are the sole sites of nucleocytoplasmic transport."
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Patient mutations disrupt NPC targeting while leaving gross NPC structure intact.
"A variety of disease-associated missense, nonsense, and frameshift mutations failed to localize to NPCs and were found predominantly in the cytoplasm."
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The authors proposed a regulatory role in nucleocytoplasmic transport.
"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."
Defining the membrane proteome of NK cells.
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AAAS was identified in a high-throughput membrane proteomics data set; the paper cautions that many identified proteins may only be transiently membrane-associated.
"The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes."
Proteomic characterization of the human sperm nucleus.
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AAAS was detected in an isolated sperm nucleus proteomics data set.
"With this approach, 403 different proteins have been identified from the isolated sperm nuclei."
Translocation of Influenza A virus nonstructural protein 1 (NS1A) into the nucleus
Rev multimer-bound HIV mRNA:Crm1:Ran:GTP complex associates with the NPC
Translocation of nuclear RNA transport complex to cytoplasm
NPC transports GCK1:GCKR from cytosol to nucleoplasm
Export of Spliced Viral mRNA
NEK6/NEK7 phosphorylates NUP98
CDK1 phosphorylates NUP98
RANBP2 SUMOylates SP100 with SUMO2
RANBP2 SUMOylates SP100 with SUMO1
RANBP2 SUMOylates PML with SUMO2
RANBP2 SUMOylates RANBP2 with SUMO1
RANBP2 SUMOylates RANBP2 with SUMO2
RANBP2 (NUP358) SUMOylates HNRNPC with SUMO1
RANBP2 SUMOylates HDAC4 with SUMO1
RANBP2 SUMOylates HDAC4 with SUMO2,3
RANBP2 SUMOylates CDCA8 (Borealin) and PIAS3 SUMOylates AURKB (Aurora-B)
RANBP2 SUMOylates PML with SUMO1
RANBP2 SUMOylates MDM2 with SUMO1
NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm
Defective NPC does not transport GCK1:GKRP from cytosol to nucleoplasm
tRNA:XPOT:RAN:GTP translocates from the nucleus to the cytosol
Docking of the TAP:EJC Complex with the NPC
Transport of the export-competent mRNP complex through the NPC
mRNP complex dissociates from cytosolic face of NPC
HCMV Nuclear Pore Docking
Transport of HCMV DNA Into the Nucleus
SARS-CoV-2 6 binds NUP98:RAE1 within NPC
Mutant WD-repeat protein in triple-A syndrome.
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AAAS encodes ALADIN, a WD-repeat protein mutated in triple-A syndrome.
"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."
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Expression in affected neuroendocrine and cerebral structures supports developmental and neurological relevance.
"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."
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.
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Loss-of-function AAAS mutations cause triple-A syndrome.
"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."
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AAAS is expressed in neuroendocrine and gastrointestinal structures affected in disease.
"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."
Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS.
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AAAS has a shorter splice variant that remains broadly expressed.
"RT-PCR analysis in our work revealed that AAAS-v2 and AAAS-v1 were ubiquitously detected in human multiple tissue cDNA (MTC) panels (CLONTECH)."
The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope.
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ALADIN is anchored in the NPC through NDC1.
"We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC."
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Loss of ALADIN integration into the NPC is disease-relevant.
"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."
UniProtKB Q9NRG9 AAAS/ALADIN record
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UniProt summarizes ALADIN as an NPC protein with roles in AURKA/NUMA1 localization and spindle formation.
"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"
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UniProt records the nuclear pore complex, spindle pole, and nuclear envelope locations.
"Nucleus, nuclear pore complex"
Proteostasis PN projected candidate additions for AAAS
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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.
"AAAS GO:0015031 protein transport new_to_goa ok_for_propagation_to_go nuclear_proteostasis.yaml Nuclear proteostasis|Protein transport Nuclear proteostasis|Protein transport|Nuclear pore complex"
Falcon deep research report for human AAAS
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Falcon deep research summarizes AAAS/ALADIN as an NPC/nuclear-envelope scaffold whose localization is NDC1-dependent.
"ALADIN localizes to the **NPC/nuclear envelope**; proper NE/NPC targeting is **NDC1-dependent**."
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Falcon deep research treats ALADIN as a scaffold/selective transport regulator rather than an enzyme or small-molecule transporter.
"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."