Gene Ontology annotation through association of InterPro records with GO terms
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Carbohydrate deficient glycoprotein syndrome type IV: deficiency of dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase.
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Human microsomal donor/acceptor assays and human cDNA complementation identify the ALG3 reaction; the G118D defect is leaky, with residual full-length precursors.
"The defect results in the accumulation of the LLO intermediate and, due to its leaky nature, a residual formation of full-length LLOs."
Next-generation sequencing to generate interactome datasets.
Widespread macromolecular interaction perturbations in human genetic disorders.
Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular processes relevant to congenital disorders of glycosylation, cancer, neurodegeneration and a variety of further pathologies.
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The dedicated study reports ALG3 homodimers and binding to several partners, including the glycosylated CREB3 precursor.
"We disclose the building of hNOT/ALG3 homodimers"
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
ALG3 transfers Man to N-glycan precursor (GlcNAc)2 (Man)5 (PP-Dol)1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
Defective ALG3 does not add mannose to the N-glycan precursor
UniProt entry Q92685 (ALG3_HUMAN)
Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia.
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Wild-type human ALG3 rescues the patient-fibroblast biochemical defect; the associated endocrine phenotype does not establish an endocrine molecular function.
"Lentiviral complementation with wild-type hALG3 corrects the biochemical defect in the patient's fibroblasts."
Sequential cleavage of the proteins encoded by HNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, results in products acting in distinct cellular compartments.
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The study identifies processed human ALG3 species in distinct compartments; their molecular activities are not established by the localization result alone.
"We present the expression profiles and subcellular location of the two full-length proteins, their N-glycosylated forms and distinct cleavage products."
Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG.
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Patient-derived fibroblasts show altered glycan extension and increased ERAD reporter activity. Cellular experiments use one homozygous R266C line, limiting generality; they do not establish ALG3 as the degradation machinery.
"These results are consistent with increased ERAD activity in ALG3-CDG."
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The cell-based study explicitly acknowledges its single-patient-line limitation.
"our cell-based analysis was collected on one ALG3-CDG cell line, which has significant limitations."
The glycosyltransferase ALG3 is an AKT substrate that regulates protein N-glycosylation.
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Human-cell and recombinant-AKT1 assays identify ALG3 as an AKT substrate at Ser11/Ser13; this is not kinase activity performed by ALG3.
"Collectively these data demonstrate that ALG3 is an AKT substrate downstream of PI3K, and is phosphorylated at Ser11/Ser13"
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The study leaves the direct effect of phosphorylation on transferase kinetics unresolved despite positive cellular glycoprotein phenotypes.
"Studies are needed to determine whether phosphorylation of ALG3 at Ser11/Ser13 alters glycosyltransferase activity, conformation, or interactions with partner proteins."
Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core.
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Wild-type yeast ScALG3 acts on a synthetic lipid-linked Man5 substrate. The substrate-trapped structural experiment uses its low-activity D71N mutant; neither is a purified-human-ALG3 assay.
"Time courses of enzymatic activity using WT ScALG3 and Dol25-PP-GlcNAc2Man5"