Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
A human protein-protein interaction network: a resource for annotating the proteome.
Homo- and heterodimerization of APP family members promotes intercellular adhesion.
Interaction of the amyloid precursor like protein 1 with the alpha2A-adrenergic receptor increases agonist-mediated inhibition of adenylate cyclase.
Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling.
Crystal structure of amyloid precursor-like protein 1 and heparin complex suggests a dual role of heparin in E2 dimerization.
The identification of novel proteins that interact with the GLP-1 receptor and restrain its activity.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1.
Pathological alpha-synuclein transmission initiated by binding lymphocyte-activation gene 3.
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The founding report of a neuronal cell-surface receptor for alpha-synuclein preformed fibrils. LAG3, not APLP1, is the protein characterized here; APLP1 entered the field as one of the other candidate binders identified in the same screen.
"Here, we show that LAG3 (lymphocyte-activation gene 3) binds alpha-syn PFF with high affinity"
Mechanistic basis for receptor-mediated pathological alpha-synuclein fibril cell-to-cell transmission in Parkinson's disease.
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Biophysical characterization showing that the APLP1 E1 domain (like LAG3 D1) uses an alkaline surface to bind the acidic C-terminus of alpha-synuclein, with strong preference for the fibrillar over the monomeric state. This is the most direct molecular evidence that APLP1 binds pathological alpha-synuclein.
"LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus"
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Both LAG3 and APLP1 are described as preferentially binding the amyloid rather than the monomeric form of alpha-synuclein.
"can preferentially bind alpha-syn in the amyloid over monomeric state to initiate cell-to-cell transmission"
Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein.
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Aplp1 is reported to act through a complex with Lag3 to support binding, internalization, transmission and toxicity of pathological alpha-synuclein. The functional claim for APLP1 is therefore framed as partner-dependent rather than as an autonomous receptor.
"amyloid beta precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding, internalization, transmission, and toxicity of pathologic alpha-syn"
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The in vivo genetic evidence is from a double knockout; no single-Aplp1 knockout result separating APLP1 from LAG3 is reported in the abstract.
"Deletion of both Aplp1 and Lag3 eliminates the loss of dopaminergic neurons"
Author Correction: Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein.
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Correction to PMID:38821932. The change is a statistical/figure-legend correction to Fig. 4 (anti-Lag3 versus Lag3-null internalization comparisons), not a retraction or a change to the Aplp1 conclusion.
"The original version of this Article contained an error in Fig. 4"
LAG3 is not expressed in human and murine neurons and does not modulate alpha-synucleinopathies.
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No LAG3 expression was detected in human or mouse neurons, and LAG3 depletion or knockout did not modify alpha-synuclein pathology in the models tested. This does not test APLP1, but it undercuts the LAG3 partner on which the published APLP1 mechanism depends.
"we found no evidence for LAG3 expression by neurons"
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The authors conclude that the proposed LAG3 role in alpha-synuclein spreading does not generalize.
"These data suggest that the proposed role of LAG3 in the spreading of alpha-synucleinopathies is not universally valid."
Neuronal FAM171A2 mediates alpha-synuclein fibril uptake and drives Parkinson's disease.
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An independent candidate neuronal receptor for alpha-synuclein fibrils, FAM171A2, binding the alpha-synuclein C-terminus electrostatically with strong fibril selectivity - the same binding logic reported for APLP1 E1 and LAG3 D1.
"Our findings identified FAM171A2 as a potential receptor for the neuronal uptake of alpha-syn fibrils"
Binding domains of alpha-synuclein receptors with monomeric/oligomeric alpha-synuclein: Implications for Parkinson's disease.
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Review/modelling paper that frames FAM171A2, LAG3 and APLP1 as the three candidate neuronal mediators of alpha-synuclein fibril uptake.
"have been identified as critical mediators of alpha-syn preformed fibril (PFF) uptake, propagation, and neurotoxicity"
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AlphaFold3 modelling predicted APLP1 complexes with monomeric and hexameric alpha-synuclein but failed for LAG3, leading the authors to propose APLP1 as an adaptor for LAG3. This is an in silico prediction, not experimental evidence.
"The APLP1 was predicted to interact with both monomeric and hexameric alpha-syn proteins."