Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Combined Automated Annotation using Multiple IEA Methods
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
Serine biosynthesis defect due to haploinsufficiency of PHGDH causes retinal disease.
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Human PHGDH enzymatic activity was directly assayed (3-phosphoglycerate to 3-phosphohydroxypyruvate with NAD+ reduction), and pathogenic variants reduced phosphoglycerate dehydrogenase activity, confirming the core molecular function.
"Enzyme activity was determined using 3-phosphoglycerate as a substrate and monitoring the reduction of the cofactor NAD+ to NADH"
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A loss-of-function PHGDH variant reduced glucose-derived flux into serine and glycine and lowered cellular serine, supporting PHGDH's role in L-serine biosynthesis.
"indicating decreased synthesis of serine/glycine via PHGDH"
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis.
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Original clinical/biochemical description of 3-phosphoglycerate dehydrogenase deficiency: patient fibroblasts showed decreased 3-PGDH activity, establishing PHGDH as the first step of serine biosynthesis.
"a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase"
Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer's disease.
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Claims an enzyme-independent, transcriptional-regulator moonlighting role for PHGDH in astrocytes, driving amyloid pathology in mice and human brain organoids. Catalysis was excluded using an active-site (R236Q) enzymatic-dead mutant.
"modulates AD pathology in mice and human brain organoids independent of its enzymatic activity"
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The claimed activity is explicitly described as previously uncharacterized.
"PHGDH has an uncharacterized role in transcriptional regulation"
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The proposed DNA-binding element is a helix-helix-turn-helix subdomain inside the Rossmann-fold nucleotide-binding domain, identified from an AlphaFold model by structural similarity to a TALE homeodomain - i.e. a predicted, not a solved, DNA-binding motif.
"which exhibits structural similarity to the three amino acid loop extension (TALE) homeodomain, a DNA-binding structural motif"
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Nuclear localization of PHGDH is reported in astrocytes but not in hESCs or HEK293T cells, where localization was cytosolic as expected for the serine-biosynthesis enzyme.
"PHGDH exhibited both cytosolic and nuclear localization in astrocytes"
RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease.
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Claims a second, distinct moonlighting activity for PHGDH - sequence-specific RNA binding to the EIF2AK1 3'UTR - that recruits EIF2AK1 to EIF2alpha and thereby promotes BACE1 translation and amyloid-beta production.
"PHGDH binds the 3'UTR of EIF2AK1 mRNA, enabling the physical interaction between PHGDH and the EIF2AK1 protein"
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The new mechanism is asserted to be independent not only of catalysis but also of the transcriptional role the same group reported the previous year, so the two moonlighting mechanisms are presented as mutually independent rather than as one mechanism refined.
"independent of its canonical enzymatic or transcriptional roles"
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A specific RNA-binding surface within PHGDH is claimed to be required.
"this process requires a specific RNA-binding surface within PHGDH and the EIF2AK1 3'UTR"
Correction for Chen et al., RNA-binding activity of PHGDH drives amyloid-beta production in a human brain organoid model of sporadic Alzheimer's disease.
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The correction is purely editorial - the misspelling of a reviewer's name. No data, figure or scientific conclusion of PMID:41701839 was corrected.
"The authors note that the reviewer name Andrew Piper should instead appear as Andrew Pieper."
PHGDH tetramer dehydrogenates 3PG