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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Cloning and sequencing of the cDNA encoding a human testis phospholipid hydroperoxide glutathione peroxidase.
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Original cloning of human GPX4 from testis library
"A human cDNA that encodes a polypeptide that has 94% deduced amino-acid sequence identity to porcine phospholipid hydroperoxide glutathione peroxidase was cloned from a testis library"
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94% sequence identity to porcine PHGPx
"A human cDNA that encodes a polypeptide that has 94% deduced amino-acid sequence identity to porcine phospholipid hydroperoxide glutathione peroxidase"
Evidence for the presence of phospholipid hydroperoxide glutathione peroxidase in human platelets: implications for its involvement in the regulatory network of the 12-lipoxygenase pathway of arachidonic acid metabolism.
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First demonstration of PHGPx protein and activity in human platelets
"Here we show for the first time the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPx) protein and its activity in platelets"
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PHGPx involved in 12-lipoxygenase pathway regulation
"We therefore believe that both GPx-1 and PHGPx are involved in the regulatory network of the 12-lipoxygenase pathway in platelets and other mammalian cells"
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Reduces 12-HpETE to 12-HETE
"The 12-lipoxygenase pathway of arachidonic acid metabolism in platelets and other cells is bifurcated into a reduction route yielding 12-hydroxyeicosatetraenoic acid (12-HETE)"
Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4).
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Crystal structure of human GPX4 at 1.55 A resolution
"we solved the crystal structure of the catalytically active U46C mutant of human GPx4 to 1.55 A resolution"
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Monomeric protein with thioredoxin-like fold
"X-ray data indicated a monomeric protein consisting of four alpha-helices and seven beta-strands"
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Catalytic triad functional importance
"Multiple mutations of the catalytic triad indicated its functional importance"
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Strong tendency toward polymerization
"Like the wild-type enzyme, the U46C mutant exhibits a strong tendency toward protein polymerization, which was prevented by reductants"
Large-scale proteomics and phosphoproteomics of urinary exosomes.
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GPX4 identified in urinary exosomes
"Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes"
Proteomic characterization of the human sperm nucleus.
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GPX4 identified in sperm nucleus
"With this approach, 403 different proteins have been identified from the isolated sperm nuclei"
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Relevance for epigenetics and development
"This provides additional information about the nuclear proteins that are potentially relevant for epigenetic marking, proper fertilization and embryo development"
Identification of sperm head proteins involved in zona pellucida binding.
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GPX4 identified in sperm head as zona pellucida interacting protein
"We identified proteins that are glycolytic enzymes such as pyruvate kinase 3, enolase 1, glyceraldehyde-3-phosphate dehydrogenase, aldolase A, triosephosphate isomerase, detoxification enzymes such as GSTM or phospholipid hydroperoxide glutathione peroxidase, ion channels such as VDAC2"
Regulation of ferroptotic cancer cell death by GPX4.
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GPX4 is central regulator of ferroptosis
"GPX4 overexpression and knockdown modulated the lethality of 12 ferroptosis inducers, but not of 11 compounds with other lethal mechanisms"
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GPX4 is essential regulator of ferroptotic cell death
"Thus, GPX4 is an essential regulator of ferroptotic cancer cell death"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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GPX4 identified in mitochondrial proteome
"Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases"
Side-by-side comparison of recombinant human glutathione peroxidases identifies overlapping substrate specificities for soluble hydroperoxides.
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GPX4 is the only GPX isoform able to reduce phosphatidylcholine hydroperoxide
"GPX4 was clearly the only isoform able to reduce phosphatidylcholine hydroperoxide"
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GPX4 also reduces H2O2 and other soluble hydroperoxides
"small soluble hydroperoxides such as H2O2, cumene hydroperoxide, and tert-butyl hydroperoxide were reduced by all three isoforms, but with approximately 10-fold higher efficiency for GPX1 in comparison to GPX2 and GPX4"
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GPXs important for reducing hydroperoxides
"The GPXs are important for reducing hydroperoxides in a glutathione-consuming manner and thus regulate cellular redox homeostasis"
PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation.
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GPX4 stability regulated by hydroxylation
"PSAT1 elevates GPX4 stability by promoting alpha-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation"
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GPX4 regulation of ferroptosis demonstrated in vivo
"In mice, reconstitution of PSAT1 S337A or GPX4 P159A promotes ferroptosis and suppresses triple-negative breast cancer (TNBC) progression"
12R-HpETE is reduced to 12R-HETE by GPX1/2/4
12S-HpETE is reduced to 12S-HETE by GPX1/2/4
Biosynthesis of D-series resolvins
GPX4-2 reduces 18(S)-HpEPE to 18(S)-HEPE
GPX4-2 reduces 18(R)-HpEPE to 18(R)-HEPE
Biosynthesis of E-series 18(S)-resolvins
Biosynthesis of aspirin-triggered D-series resolvins
GPX4-2 reduces 17(R)-Hp-DHA to 17(R)-HDHA
GPX4-2 reduces 17(S)-Hp-DHA to 17(S)-HDHA
Biosynthesis of E-series 18(R)-resolvins
Deep research report on GPX4
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mGPX4 targets mitochondria
"mGPX4 targets mitochondria and preserves mitochondrial membrane integrity"
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GPX4 is central effector of ferroptosis suppression
"GPX4 is the central effector of the system xc-/GSH/GPX4 axis"