Affinage

SELENOP

Selenoprotein P · UniProt P49908

Round 2 corrected
Length
381 aa
Mass
43.2 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SELENOP encodes selenoprotein P, a liver-derived, heparin-binding extracellular glycoprotein that serves as the principal selenium transport protein in plasma, delivering selenium to privileged tissues—brain, testis, and kidney—via receptor-mediated endocytosis through apoER2 and LRP1, with heparan sulfate proteoglycan co-binding and lysosomal processing required for selenium release (PMID:22761431, PMID:17961124, PMID:23038251). Its N-terminal thioredoxin-fold domain harbors a selenocysteine at position 40 (UYLC motif) that confers thioredoxin reductase 1–coupled peroxidase activity and phospholipid hydroperoxide glutathione peroxidase activity in extracellular fluids, while its selenium-rich C-terminal domain (up to 10 selenocysteine residues) constitutes the selenium cargo (PMID:9915822, PMID:24434121, PMID:8421687). Beyond selenium homeostasis, SELENOP functions as a hepatokine that impairs insulin signaling and suppresses exercise adaptation by inactivating AMPK in liver and skeletal muscle through LRP1, promotes hepatic lipid accumulation via the AMPK/ACC axis, and modulates WNT/β-catenin signaling through direct interaction with the co-receptors LRP5/LRP6 in colonic epithelium (PMID:21035759, PMID:28263310, PMID:33094480, PMID:37166989). Loss of SELENOP causes cerebellar atrophy, ataxia, and seizures due to failure of selenium delivery to the CNS, as demonstrated in knockout mice and a naturally occurring canine deletion (PMID:34339417, PMID:36182809).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Resolving how a single mRNA encodes 10 selenocysteine residues, cloning of human SELENOP revealed two 3′-UTR SECIS elements sufficient to direct readthrough of all in-frame UGA codons, establishing the gene's unique translational architecture.

    Evidence cDNA cloning from human liver/heart libraries with comparative sequence and secondary-structure analysis of the 3′ UTR

    PMID:8421687

    Open questions at the time
    • Mechanism of ribosomal processivity through 10 consecutive UGA codons not resolved
    • Relative contribution of each SECIS element to decoding efficiency unknown
  2. 1994 High

    Biochemical purification established that selenoprotein P is a selenium-rich, heparin-binding extracellular glycoprotein accounting for the majority of plasma selenium, with rapid turnover consistent with a transport function.

    Evidence Purification from rat and human plasma by immunoaffinity and heparin-agarose chromatography; ⁷⁵Se radiolabeling; selenium content and half-life measurements

    PMID:7931697 PMID:8142465

    Open questions at the time
    • Tissue-specific uptake mechanism unknown at this stage
    • Glycosylation function not determined
  3. 1999 High

    Answering whether SELENOP possesses enzymatic activity beyond selenium transport, kinetic analysis demonstrated that purified SELENOP reduces phospholipid hydroperoxides via a glutathione-dependent ping-pong mechanism, establishing it as an extracellular antioxidant enzyme.

    Evidence In vitro enzymatic assay with purified human plasma SELENOP using various hydroperoxide substrates and thiol reductants

    PMID:9915822

    Open questions at the time
    • Active-site selenocysteine residue responsible for peroxidase activity not yet identified by mutagenesis
    • Physiological relevance of extracellular peroxidase activity in vivo undetermined
  4. 2002 High

    Immunodepletion/reconstitution experiments showed that SELENOP, not extracellular GPx, is the essential selenium supply protein in serum, as its removal abolished cellular selenoenzyme activities that were restored only by SELENOP repletion.

    Evidence Immunodepletion of SELENOP or GPx3 from human serum followed by culture of Jurkat cells and measurement of intracellular GPx and TrxR activities

    PMID:12423375

    Open questions at the time
    • Receptor-mediated uptake mechanism not yet identified
    • Whether selenium delivery requires full-length protein or C-terminal domain alone unknown
  5. 2008 High

    Genetic rescue experiments answered whether liver is the physiological source of circulating SELENOP: hepatocyte-specific transgenic expression of SEPP1 in Sepp-null mice restored plasma selenium, rescued neurological defects, and recovered selenoenzyme activity in brain, testis, and kidney.

    Evidence Transgenic mice expressing human SEPP1 under a hepatocyte-specific promoter in Sepp⁻/⁻ background; tissue selenium and selenoenzyme activity measurements; neurological and fertility phenotyping

    PMID:17961124

    Open questions at the time
    • Local (non-hepatic) SELENOP production contribution not quantified
    • Whether other organs can compensate under specific conditions unclear
  6. 2012 High

    Receptor identification and conditional knockout studies defined the molecular mechanism of SELENOP uptake and whole-body selenium distribution: apoER2 mediates endocytosis of SELENOP's selenium-rich C-terminal domain in muscle cells requiring heparan sulfate proteoglycans and lysosomal processing, while hepatocyte-specific Sepp1 deletion confirmed the liver as the dominant source controlling systemic selenium balance.

    Evidence Affinity pulldown with mass spectrometry receptor identification; siRNA knockdown of apoER2 and LRP1; ⁷⁵Se uptake assays with inhibitors; conditional hepatocyte-specific Sepp1 knockout mice with tissue selenium and urinary selenium measurements

    PMID:22761431 PMID:23038251

    Open questions at the time
    • Brain-specific uptake receptor (apoER2 vs. megalin) hierarchy not fully resolved
    • Structural basis of SELENOP–apoER2 interaction unknown
  7. 2010 High

    Discovery that SELENOP acts as a hepatokine causing insulin resistance opened a new functional dimension: purified SELENOP impaired insulin signaling through AMPK inactivation, and Selenop knockout or knockdown improved glucose tolerance in mice.

    Evidence Human liver transcriptomic correlation; purified SELENOP administration to hepatocytes and myocytes; Selenop⁻/⁻ mice; siRNA knockdown; AMPK activity and insulin signaling assays

    PMID:21035759

    Open questions at the time
    • Direct molecular target through which SELENOP inactivates AMPK not identified
    • Whether hepatokine function is selenium-dependent or protein-intrinsic not resolved
  8. 2014 High

    Active-site mutagenesis resolved the catalytic residue responsible for SELENOP peroxidase activity: Sec40 in the N-terminal UYLC motif is essential for TrxR1-coupled reduction of hydroperoxides, and truncated N-terminal fragments retain this activity.

    Evidence Purification of N-terminal fragments from megalin⁻/⁻ mouse urine; U40S mutagenesis; TrxR1-coupled NADPH oxidation assay

    PMID:24434121

    Open questions at the time
    • Whether the peroxidase activity is physiologically relevant in renal tubule protection not tested in vivo
  9. 2017 High

    Identification of LRP1 as the muscle receptor mediating SELENOP's exercise-suppressive effect explained how a hepatokine impairs ROS-dependent AMPK–PGC-1α exercise adaptation: muscle-specific LRP1 knockout blunted SELENOP's inhibition of exercise-induced signaling.

    Evidence Selenop⁻/⁻ mice with exercise protocols; muscle-specific LRP1 conditional KO; LRP1-Fc blocking in myotubes; ROS, AMPK phosphorylation, and PGC-1α expression measurements

    PMID:28263310

    Open questions at the time
    • Whether SELENOP-LRP1 signaling differs from selenium transport through apoER2 not mechanistically dissected
    • Downstream ROS target linking SELENOP to AMPK suppression not identified
  10. 2019 Medium

    Transcriptional regulation of SELENOP was defined: FOXO1 directly occupies the SELENOP promoter, and AMPK/SIRT1 signaling suppresses SELENOP transcription, creating a feedback loop where the hepatokine's own targets regulate its expression.

    Evidence ChIP-qPCR for FOXO1 on SELENOP promoter; AMPK and SIRT1 siRNA epistasis in palmitate-treated human primary hepatocytes; recombinant SELENOP reconstitution

    PMID:31246318

    Open questions at the time
    • FOXO1 binding site not mapped at single-nucleotide resolution
    • Whether SIRT1 acts directly on FOXO1 acetylation at the SELENOP promoter not shown
  11. 2021 High

    A natural complete gene deletion of SELENOP in dogs causing cerebellar atrophy and ataxia demonstrated that SELENOP is essential for CNS selenium supply across species, extending the knockout phenotype from mice to a large-animal model.

    Evidence Linkage and homozygosity mapping; whole-genome sequencing identifying a 17.3 kb deletion; blood selenium measurement; histopathology; genotyping of >600 Belgian Shepherds

    PMID:34339417

    Open questions at the time
    • Whether partial loss-of-function variants in humans cause neurological disease not yet demonstrated
    • Contribution of CNS-local SELENOP expression to the canine phenotype not assessed
  12. 2022 High

    Dietary selenium dose–response experiments with Selenop⁻/⁻ mice revealed that SELENOP is specifically required to preserve parvalbumin interneurons, linking selenium transport to GABAergic circuit integrity and epileptogenesis.

    Evidence Selenop⁻/⁻ mice on graded selenium diets; video-EEG seizure detection; histological quantification of parvalbumin interneurons; brain GPx activity; hepatocyte-specific SELENOP transgenic rescue

    PMID:36182809

    Open questions at the time
    • Molecular mechanism of selective parvalbumin interneuron vulnerability not defined
    • Whether selenoprotein deficiency in these neurons is cell-autonomous or circuit-driven unknown
  13. 2022 High

    HNF4α was identified as a direct transcriptional activator of SELENOP in hepatocytes, with fatty acid (lauric acid) stimulation increasing HNF4α occupancy at the SELENOP promoter and linking dietary lipids to hepatokine production.

    Evidence Luciferase promoter assay; ChIP assay for HNF4α; Hnf4α siRNA epistasis; in vivo mouse liver validation

    PMID:35499234

    Open questions at the time
    • Whether other fatty acids act through the same HNF4α mechanism not systematically tested
    • Interplay between HNF4α and FOXO1 on the SELENOP promoter not resolved
  14. 2023 High

    Discovery that SELENOP directly binds WNT co-receptors LRP5/LRP6 to modulate canonical WNT signaling in the colon expanded SELENOP's functional repertoire beyond selenium transport and metabolic hepatokine activity to include morphogenetic signaling in colorectal epithelium.

    Evidence Single-cell RNA-seq; conditional intestinal Apc-deletion plus Selenop KO mouse model; tumor organoid WNT target gene expression; SELENOP restoration; protein-protein interaction mapping for SELENOP–LRP5/6

    PMID:37166989

    Open questions at the time
    • Whether SELENOP–LRP5/6 interaction is selenium-dependent or mediated by the protein scaffold not determined
    • Structural basis of SELENOP–LRP5/6 binding unknown
    • Effect on WNT signaling in non-intestinal tissues not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the direct molecular mechanism by which SELENOP inactivates AMPK (whether selenium-dependent or protein-intrinsic), the structural basis of SELENOP interactions with its receptors (apoER2, LRP1, LRP5/6), whether human loss-of-function variants cause neurological disease, and how the dual antioxidant-enzyme and selenium-transport functions are coordinated in vivo.
  • No crystal structure of SELENOP or SELENOP–receptor complexes available
  • Human genetic loss-of-function phenotype not established
  • Selenium-dependence of hepatokine and WNT-modulatory functions not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 4 GO:0098772 molecular function regulator activity 3 GO:0016209 antioxidant activity 2 GO:0016491 oxidoreductase activity 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2
Partners
FOXO1HNF4ALRP1LRP5LRP6LRP8TXNRD1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Human selenoprotein P mRNA contains two conserved stem-loop structures in its 3' untranslated region (SECIS elements), one for each domain, establishing that a separate stem-loop is not required for each of the 10 selenocysteine residues encoded by UGA codons in the open reading frame. cDNA cloning and sequencing of human selenoprotein P from liver/heart libraries; comparative sequence analysis with rat cDNA; secondary structure prediction of 3' UTR Proceedings of the National Academy of Sciences of the United States of America High 8421687
1994 Selenoprotein P is a selenium-rich extracellular glycoprotein containing selenocysteine residues; purified rat selenoprotein P contains ~7.5 selenium atoms per molecule, and in selenium-replete rats it contains ~65% of plasma selenium with rapid turnover (plasma half-life of 3–4 h for 75Se). Protein purification from rat/human plasma; 75Se radiolabeling; SDS-PAGE; selenium content measurement; Northern blot for tissue expression and selenium-deficiency regulation The Journal of nutrition High 7931697
1994 Selenoprotein P was purified from human plasma by immunoaffinity chromatography followed by heparin-agarose chromatography, yielding two bands (61 and 55 kDa) that are both glycoproteins; the protein accounts for approximately one-third of total plasma selenium and binds heparin. Immunoaffinity chromatography with monoclonal antibodies; heparin-agarose chromatography; SDS-PAGE; carbohydrate staining; enzymatic deglycosylation; 75Se-labeled SELENOP from HepG2 cells as tracer Biochimica et biophysica acta High 8142465
1999 Purified human selenoprotein P functions as a phospholipid hydroperoxide glutathione peroxidase in extracellular fluids: it reduces phospholipid hydroperoxides (but not H2O2 or tert-butyl hydroperoxide) using glutathione and other thiol reductants via a tert-uni ping-pong kinetic mechanism. Conventional purification of selenoprotein P from human plasma; enzymatic assays with various hydroperoxide substrates and reducing agents; kinetic analysis The Journal of biological chemistry High 9915822
2002 Selenoprotein P is the primary selenium supply protein in serum: immunodepletion of selenoprotein P (but not extracellular GPx) from human serum severely depleted cellular selenium and glutathione peroxidase/thioredoxin reductase activities in Jurkat T-lymphoma cells cultured in that serum; repletion with purified selenoprotein P restored activity. Immunodepletion of specific selenoproteins from human serum; cell culture with depleted/reconstituted serum; measurement of Se-dependent enzyme activities (GPx, TrxR); Se content assay European journal of biochemistry High 12423375
2008 Liver-derived circulating selenoprotein P is the main selenium transport form that supplies the kidney, testis, and brain; hepatocyte-specific transgenic expression of SEPP1 in Sepp-/- mice rescued neurological defects (ataxia, seizures) and male infertility and increased selenium and selenoenzyme activities in plasma, kidney, testis, and brain, demonstrating that plasma SeP from hepatocytes supports selenium-privileged tissues. Transgenic rescue experiment: human SEPP1 under hepatocyte-specific transthyretin promoter in Sepp-/- mice; selenium content measurement in tissues; selenoenzyme activity assays; neurological phenotyping; fertility testing The Biochemical journal High 17961124
2010 Selenoprotein P (SeP) is a liver-derived hepatokine that causes insulin resistance: hepatic SeP mRNA correlated with insulin resistance in humans; purified SeP impaired insulin signaling and glucose metabolism in hepatocytes and myocytes; genetic deletion or siRNA knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice; the metabolic actions were mediated at least partly by inactivation of AMP-activated protein kinase (AMPK). SAGE and DNA chip analysis of human liver; administration of purified SeP to cultured cells and mice; SeP knockout mice; siRNA knockdown; insulin signaling assays; glucose tolerance tests; AMPK activity assays Cell metabolism High 21035759
2012 Hepatocyte-produced selenoprotein P is central to whole-body selenium homeostasis: selective deletion of Sepp1 in hepatocytes lowered plasma Sepp1 to 10% of controls, increased urinary selenium excretion reducing whole-body selenium, and under selenium-deficient conditions caused liver selenium accumulation at the expense of extra-hepatic tissues. Additionally, Sepp1 synthesis is preferentially maintained over Gpx1 synthesis in hepatocytes under selenium limitation, directing selenium to peripheral tissues. Conditional hepatocyte-specific Sepp1 knockout mice (Sepp1c/c/alb-cre); plasma and tissue selenium measurement; urinary selenium excretion; selenoprotein mRNA quantification; clinical phenotyping under selenium deficiency The Journal of biological chemistry High 23038251
2012 L8 myoblast cells take up Sepp1 via an apoER2-mediated endocytic mechanism requiring binding to heparan sulfate proteoglycans; the selenium-rich C-terminal domain of Sepp1 is required for uptake and utilization; Lrp1 is present on a Sepp1-binding membrane fraction but siRNA knockdown showed it is not required for 75Se uptake from Sepp1. Lysosomal acidification is needed for Sepp1 digestion and selenium release. Sepp1-affinity column pulldown from membrane fraction; mass spectrometry identification of receptors (apoER2, Lrp1); siRNA knockdown of receptors; 75Se radiolabeled Sepp1 uptake assays; protamine/chlorate inhibition; lysosome acidification blockade; Sepp1 isoform (Δ240-361) comparison The Journal of biological chemistry High 22761431
2014 N-terminal truncation fragments of Sepp1 (designated Sepp1UF), filtered at the glomerulus and taken up by renal proximal convoluted tubule cells via megalin-mediated endocytosis, possess peroxidase activity: they catalyze NADPH oxidation when coupled with thioredoxin reductase-1 (TrxR1) and H2O2 or tert-butylhydroperoxide as terminal electron acceptors. The single selenocysteine at position 40 (in the UYLC redox-active motif of the N-terminal thioredoxin-fold domain) is essential for this activity, as shown by Sepp1(U40S) mutagenesis. Purification of urinary Sepp1 from megalin-/- mice by monoclonal antibody; mass spectrometry identification of truncation sites; TrxR1-coupled peroxidase assay with NADPH; mutagenesis (U40S selenocysteine-to-serine); comparison of full-length vs. truncated vs. mutant Sepp1 as TrxR1 substrates Free radical biology & medicine High 24434121
2016 Selenoprotein P nomenclature was standardized: the approved HGNC symbol SELENOP replaces prior symbols (SeP, SEPP1, SELP), resolving conflicts with P-selectin (SELP) and other genes. Systematic gene nomenclature review by selenoprotein experts and HUGO Gene Nomenclature Committee The Journal of biological chemistry High 27645994
2017 SeP causes exercise resistance through its muscle receptor LRP1: SeP-deficient mice showed enhanced exercise endurance, increased ROS production, AMPK phosphorylation, and PGC-1α expression in skeletal muscle. SeP treatment suppressed H2O2-induced adaptations in cultured myotubes via LRP1, and muscle-specific LRP1 knockout blunted SeP's inhibitory effects on exercise-induced AMPK phosphorylation and Ppargc1a expression in vivo. SeP knockout mice; exercise training protocols; ROS measurement; AMPK phosphorylation assay; PGC-1α/Ppargc1a expression; NAC antioxidant treatment; LRP1-Fc blocking; muscle-specific LRP1 conditional knockout mice; cultured myotube experiments; human cohort correlation Nature medicine High 28263310
2012 Elevated circulating SeP levels are inversely correlated with adiponectin in type 2 diabetes patients, and SeP knockout mice show increased blood adiponectin levels on both regular chow and high-fat diet, suggesting that liver-derived SeP suppresses adiponectin production. Cross-sectional clinical study with Spearman correlation and multiple regression; SeP knockout mice on different diets with adiponectin measurement PloS one Medium 22496878
2020 SeP participates in NAFLD pathogenesis through the AMPK/ACC pathway: siRNA knockdown of SEPP1 inhibited triglyceride accumulation by activating AMPK/ACC phosphorylation, while SEPP1 overexpression aggravated lipid accumulation and inhibited AMPK/ACC phosphorylation in HepG2 cells and in mouse NAFLD models. siRNA knockdown and overexpression of SEPP1 in HepG2 cells; in vivo NAFLD mouse model; triglyceride accumulation assay; Western blot for AMPK/ACC phosphorylation Journal of cellular physiology Medium 33094480
2019 Protectin DX reduces hepatic insulin resistance by suppressing SeP expression via AMPK/SIRT1 signaling: AMPK or SIRT1 siRNA abolished the suppressive effects of PDX on palmitate-induced SeP expression, and the mechanism involves FOXO1-mediated transcriptional regulation of SeP. Recombinant SeP reversed the improvement in insulin signaling conferred by PDX treatment. Human primary hepatocyte treatment with palmitate and PDX; siRNA knockdown of AMPK and SIRT1; FOXO1 ChIP qPCR; Western blot for insulin signaling; recombinant SeP reconstitution Clinical and experimental pharmacology & physiology Medium 31246318
2014 Exendin-4 (GLP-1 receptor agonist) reduces SEPP1 expression in hepatocytes via AMPK activation: AMPK activator AICAR negatively regulated SEPP1 and fetuin-A expression, and exendin-4 failed to suppress SEPP1 expression in cells transfected with AMPK siRNA, establishing AMPK as the effector linking GLP-1 signaling to SeP suppression. The mechanism involves reduction of palmitate-induced ER stress. HepG2 cell treatment with palmitate, tunicamycin, exendin-4, AICAR; AMPK siRNA knockdown; RT-PCR and Western blot for SEPP1, fetuin-A, ER stress markers Endocrinology and metabolism (Seoul, Korea) Medium 26194078
2021 Deletion of the entire SELENOP gene in dogs causes cerebellar atrophy and ataxia (CACA) associated with severely reduced blood selenium (~30% of wild-type), demonstrating that SELENOP is essential for selenium transport into the CNS in dogs and that its loss phenocopies but exceeds the severity of Selenop-/- knockout mice. Combined linkage and homozygosity mapping; whole genome sequencing; identification of homozygous 17.3 kb deletion encompassing the entire SELENOP coding sequence; blood selenium measurement; histopathology; genotyping of >600 Belgian Shepherd dogs PLoS genetics High 34339417
2022 SELENOP is essential for preserving parvalbumin-expressing interneuron survival under limiting selenium supply: Selenop-/- mice on the recommended dietary allowance (RDA) diet developed epileptic seizures and ataxia that were prevented by selenium supplementation or hepatocyte-specific SELENOP transgene expression; selenium supplementation restored brain glutathione peroxidase activity to control levels, and the neurological phenotype was dose- and time-dependent on selenium supply. Selenop-/- and Selenop+/- mice on varying selenium diets; video-EEG for seizure detection; behavioral phenotyping (ataxia, tremor); brain GPx activity assay; histological analysis of parvalbumin interneurons; transgenic rescue with hepatocyte-specific human SELENOP Redox biology High 36182809
2022 Lauric acid upregulates SELENOP expression in hepatocytes through HNF4α: luciferase promoter assays identified an HNF4α binding site in the SELENOP promoter, ChIP assay confirmed increased HNF4α binding upon lauric acid treatment, and Hnf4α siRNA knockdown abolished lauric acid-induced Selenop upregulation and the associated impairment of insulin-induced Akt phosphorylation. Luciferase reporter assay; ChIP assay; siRNA knockdown of Hnf4α and Selenop; computational transcription factor binding site analysis; Western blot for Akt phosphorylation; in vivo mouse liver validation American journal of physiology. Endocrinology and metabolism High 35499234
2023 SELENOP modulates canonical WNT signaling in colorectal carcinogenesis through direct protein-protein interactions with the WNT co-receptors LRP5 and LRP6: SELENOP KO in tumor organoids reduced WNT target gene expression (reversible by SELENOP restoration), SELENOP increased WNT signaling activity in CRC and non-cancer cell lines, and protein-protein interaction mapping confirmed SELENOP-LRP5/6 binding as the mechanistic basis of this effect. Single-cell RNA-seq of human colon tissue; conditional intestinal Apc-deletion plus Selenop KO mouse model; tumor organoid formation assays; WNT target gene expression; SELENOP restoration experiments; protein-protein interaction mapping (SELENOP-LRP5/6); CRC cell line WNT reporter assays The Journal of clinical investigation High 37166989
2022 Resveratrol is a potent suppressor of SELENOP expression in hepatocytes: high-throughput screening of 1861 FDA-approved drugs identified resveratrol, vidofludimus, and antimony potassium tartrate as the most potent suppressors (>3-fold reduction) of extracellular SELENOP concentrations in HepG2 cells, without affecting cell viability; RNA-seq revealed effects on metabolic pathways and vesicle trafficking. High-throughput ELISA-based drug screening (1861 compounds); dose-response characterization; cell viability assays; RNA-seq pathway analysis Redox biology Medium 36586222

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2010 A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell metabolism 461 21035759
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2016 Selenoprotein Gene Nomenclature. The Journal of biological chemistry 220 27645994
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
1999 Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p. The Journal of biological chemistry 207 9915822
2012 SEPP: SATé-enabled phylogenetic placement. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing 196 22174280
2012 Composition and evolution of the vertebrate and mammalian selenoproteomes. PloS one 183 22479358
2007 Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 169 17536041
1993 Conserved nucleotide sequences in the open reading frame and 3' untranslated region of selenoprotein P mRNA. Proceedings of the National Academy of Sciences of the United States of America 161 8421687
2009 Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Science signaling 159 20029029
2011 Serum selenoprotein P levels in patients with type 2 diabetes and prediabetes: implications for insulin resistance, inflammation, and atherosclerosis. The Journal of clinical endocrinology and metabolism 155 21677040
2019 SEP-363856, a Novel Psychotropic Agent with a Unique, Non-D2 Receptor Mechanism of Action. The Journal of pharmacology and experimental therapeutics 144 31371483
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2021 SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care. Nature communications 137 34099652
1994 Selenoprotein P. A selenium-rich extracellular glycoprotein. The Journal of nutrition 131 7931697
2017 Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle. Nature medicine 130 28263310
2002 Characterization of selenoprotein P as a selenium supply protein. European journal of biochemistry 129 12423375
2012 Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis. The Journal of biological chemistry 114 23038251
2008 Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. The Biochemical journal 113 17961124
2010 Genetic variants in selenoprotein genes increase risk of colorectal cancer. Carcinogenesis 111 20378690
2001 Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene. Cancer research 102 11280803
2010 Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 101 20852007
2004 Automated yeast two-hybrid screening for nuclear receptor-interacting proteins. Molecular & cellular proteomics : MCP 100 15604093
2004 Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis. Nutrition and cancer 97 15203372
2012 Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes. PloS one 94 22496878
1994 Purification of selenoprotein P from human plasma. Biochimica et biophysica acta 93 8142465
2016 Sex-specific and inter-individual differences in biomarkers of selenium status identified by a calibrated ELISA for selenoprotein P. Redox biology 91 28064116
2011 Roles of the 15-kDa selenoprotein (Sep15) in redox homeostasis and cataract development revealed by the analysis of Sep 15 knockout mice. The Journal of biological chemistry 83 21768092
2020 lncRNA DLEU2 acts as a miR-181a sponge to regulate SEPP1 and inhibit skeletal muscle differentiation and regeneration. Aging 80 33221762
2016 Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thrombosis and haemostasis 72 27975100
2021 Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study. NPJ schizophrenia 70 34887427
2000 Inverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP in colorectal adenomas compared with adjacent normal mucosa. Nutrition and cancer 55 10965527
2012 Long isoform mouse selenoprotein P (Sepp1) supplies rat myoblast L8 cells with selenium via endocytosis mediated by heparin binding properties and apolipoprotein E receptor-2 (ApoER2). The Journal of biological chemistry 45 22761431
2010 Racial and ethnic health disparities: evidence of discrimination's effects across the SEP spectrum. Ethnicity & health 45 20131130
1978 Identification of the Escherichia coli cell division gene sep and organization of the cell division-cell envelope genes in the sep-mur-ftsA-envA cluster as determined with specialized transducing lambda bacteriophages. Journal of bacteriology 43 338600
2013 Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics. Gene 42 24161883
2008 Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 39 19058871
2007 Molecular and phylogenetic analysis of MADS-box genes of MIKC type and chromosome location of SEP-like genes in wheat (Triticum aestivum L.). Molecular genetics and genomics : MGG 39 17846794
2014 AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. PloS one 38 25238546
2014 Expression of paralogous SEP-, FUL-, AG- and STK-like MADS-box genes in wild-type and peloric Phalaenopsis flowers. Frontiers in plant science 36 24659990
2004 Identification and characterization of the novel LysM domain-containing surface protein Sep from Lactobacillus fermentum BR11 and its use as a peptide fusion partner in Lactobacillus and Lactococcus. Applied and environmental microbiology 35 15184172
2020 SeP is elevated in NAFLD and participates in NAFLD pathogenesis through AMPK/ACC pathway. Journal of cellular physiology 34 33094480
2018 Arsenic metabolites; selenium; and AS3MT, MTHFR, AQP4, AQP9, SELENOP, INMT, and MT2A polymorphisms in Croatian-Slovenian population from PHIME-CROME study. Environmental research 34 30612060
2014 Sepp1(UF) forms are N-terminal selenoprotein P truncations that have peroxidase activity when coupled with thioredoxin reductase-1. Free radical biology & medicine 34 24434121
2011 Solubilization and folding of a fully active recombinant Gaussia luciferase with native disulfide bonds by using a SEP-Tag. Biochimica et biophysica acta 34 21945374
1999 Eleven novel sep genes of Schizosaccharomyces pombe required for efficient cell separation and sexual differentiation. Yeast (Chichester, England) 34 10392445
2021 Effect of TAAR1/5-HT1A agonist SEP-363856 on REM sleep in humans. Translational psychiatry 33 33879769
2013 Molecular evolution and patterns of duplication in the SEP/AGL6-like lineage of the Zingiberales: a proposed mechanism for floral diversification. Molecular biology and evolution 32 23938867
2021 Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856. International journal of molecular sciences 31 33923479
2015 Sep(t)arate or not – how some cells take septin-independent routes through cytokinesis. Journal of cell science 31 25690008
2013 SEPP1 influences breast cancer risk among women with greater native american ancestry: the breast cancer health disparities study. PloS one 31 24278290
2007 Structural insights into the second step of RNA-dependent cysteine biosynthesis in archaea: crystal structure of Sep-tRNA:Cys-tRNA synthase from Archaeoglobus fulgidus. Journal of molecular biology 31 17512006
2014 The anti-lung cancer activity of SEP is mediated by the activation and cytotoxicity of NK cells via TLR2/4 in vivo. Biochemical pharmacology 29 24630931
2022 TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT1A receptor agonist SEP-383856. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 28 36100653
2020 Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components. Oxidative medicine and cellular longevity 28 32377302
1985 Extraction and fractionation of bile acids and their conjugates using pre-packed microparticulate silica cartridges (Sep-Pak Sil and Bond-Elut C18). Journal of chromatography 27 4066870
2022 A Multi-Disulfide Receptor-Binding Domain (RBD) of the SARS-CoV-2 Spike Protein Expressed in E. coli Using a SEP-Tag Produces Antisera Interacting with the Mammalian Cell Expressed Spike (S1) Protein. International journal of molecular sciences 26 35163624
2021 Binding of SEP-363856 within TAAR1 and the 5HT1A receptor: implications for the design of novel antipsychotic drugs. Molecular psychiatry 26 34376825
2021 The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review. International journal of molecular sciences 26 34830040
2020 Protein Phosphatase-1 Complex Disassembly by p97 is Initiated through Multivalent Recognition of Catalytic and Regulatory Subunits by the p97 SEP-domain Adapters. Journal of molecular biology 26 33058883
2001 Independent short-term variability of spike-like (600 Hz) and postsynaptic (N20) cerebral SEP components. Neuroreport 26 11209948
2018 Fabrication and Characterization of Recombinant Silk-Elastin-Like-Protein (SELP) Fiber. Macromolecular bioscience 25 30417967
2014 Functional and evolutionary analysis of the AP1/SEP/AGL6 superclade of MADS-box genes in the basal eudicot Epimedium sagittatum. Annals of botany 25 24532606
2018 Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer. The Prostate 24 29314169
2002 SEP-1 - a subtilisin-like serine endopeptidase from germinated seeds of Hordeum vulgare L. cv. Morex. Planta 24 12355148
2023 Efficacy, safety, and tolerability of ulotaront (SEP-363856, a trace amine-associated receptor 1 agonist) for the treatment of schizophrenia and other mental disorders: a systematic review of preclinical and clinical trials. Expert opinion on investigational drugs 23 37096491
2018 A SEP tag enhances the expression, solubility and yield of recombinant TEV protease without altering its activity. New biotechnology 23 29448030
2016 SEP enhanced the antitumor activity of 5-fluorouracil by up-regulating NKG2D/MICA and reversed immune suppression via inhibiting ROS and caspase-3 in mice. Oncotarget 22 27385218
2011 Erythrocyte remodeling in Plasmodium berghei infection: the contribution of SEP family members. Traffic (Copenhagen, Denmark) 22 22106924
1988 Chromatography of serum on Sep-pak C18 corrects falsely elevated vitamin D metabolite levels measured by protein binding assay. Clinica chimica acta; international journal of clinical chemistry 22 2846207
2024 SEP-AlgPro: An efficient allergen prediction tool utilizing traditional machine learning and deep learning techniques with protein language model features. International journal of biological macromolecules 21 38871100
2017 SEP-class genes in Prunus mume and their likely role in floral organ development. BMC plant biology 21 28086797
2016 The Synergistic Effect of Serine with Selenocompounds on the Expression of SelP and GPx in HepG2 Cells. Biological trace element research 21 26944060
2013 Bringing the science of proteins into the realm of organic chemistry: total chemical synthesis of SEP (synthetic erythropoiesis protein). Angewandte Chemie (International ed. in English) 21 24127351
2006 Occurrence of sep insecticidal toxin complex genes in Serratia spp. and Yersinia frederiksenii. Applied and environmental microbiology 21 17021209
1983 An evaluation of the use of Sep-Pak C18 cartridges for the extraction of vitamin D3 and some of its metabolites from plasma and urine. Journal of steroid biochemistry 21 6312196
2019 Protectin DX ameliorates palmitate-induced hepatic insulin resistance through AMPK/SIRT1-mediated modulation of fetuin-A and SeP expression. Clinical and experimental pharmacology & physiology 20 31246318
2021 A Randomized, Double-blind, Placebo-controlled Proof-of-Concept Trial to Evaluate the Efficacy and Safety of Non-racemic Amisulpride (SEP-4199) for the Treatment of Bipolar I Depression. Journal of affective disorders 19 34614447
2016 Accurate Quantification of Selenoprotein P (SEPP1) in Plasma Using Isotopically Enriched Seleno-peptides and Species-Specific Isotope Dilution with HPLC Coupled to ICP-MS/MS. Analytical chemistry 19 27108743
2014 Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression. PloS one 19 25147926
2014 SEPP1 gene variants and abdominal aortic aneurysm: gene association in relation to metabolic risk factors and peripheral arterial disease coexistence. Scientific reports 19 25395084
2009 Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE. Genes and immunity 19 19404301
2003 Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques. Bioorganic & medicinal chemistry letters 19 14592478
1996 Disruption of the serine proteinase gene (sep) in Aspergillus flavus leads to a compensatory increase in the expression of a metalloproteinase gene (mep20). Journal of bacteriology 19 8682796
2023 Ribosomal incorporation of negatively charged d-α- and N-methyl-l-α-amino acids enhanced by EF-Sep. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 17 36633283
2023 SELENOP modifies sporadic colorectal carcinogenesis and WNT signaling activity through LRP5/6 interactions. The Journal of clinical investigation 17 37166989
2021 Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs. PLoS genetics 17 34339417
2018 Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice. Scientific reports 17 29317734
2009 SELP and SELPLG genetic variation is associated with cell surface measures of SELP and SELPLG: the Atherosclerosis Risk in Communities Carotid MRI Study. Clinical chemistry 17 19395438
2007 Induced expression of the Serratia entomophila Sep proteins shows activity towards the larvae of the New Zealand grass grub Costelytra zealandica. FEMS microbiology letters 17 17714480
1987 Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels. Journal of the neurological sciences 17 2831310
2023 In Vitro Comparison of Ulotaront (SEP-363856) and Ralmitaront (RO6889450): Two TAAR1 Agonist Candidate Antipsychotics. The international journal of neuropsychopharmacology 16 37549917
2016 Selenium levels in human breast carcinoma tissue are associated with a common polymorphism in the gene for SELENOP (Selenoprotein P). Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 16 27908419
2012 SeP, ApoER2 and megalin as necessary factors to maintain Se homeostasis in mammals. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 16 22683052
2011 First steps towards a Zn/Co(III)sep-driven P450 BM3 reactor. Applied microbiology and biotechnology 16 21562982
2015 DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism. European journal of nutrition 15 26658762
2022 High throughput drug screening identifies resveratrol as suppressor of hepatic SELENOP expression. Redox biology 14 36586222
2021 Silver-sepiolite (Ag-Sep) hybrid reinforced active gelatin/date waste extract (DSWE) blend composite films for food packaging application. Food chemistry 14 34500208
2019 Comment on the: Molecular mechanism of CAT and SOD activity change under MPA-CdTe quantum dots induced oxidative stress in the mouse primary hepatocytes (Spectrochim Acta A Mol Biomol Spectrosc. 2019 Sep 5; 220:117104). Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 14 31865110
2016 Protective Action of Se-Supplement Against Acute Alcoholism Is Regulated by Selenoprotein P (SelP) in the Liver. Biological trace element research 14 27334433
2014 Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK. Endocrinology and metabolism (Seoul, Korea) 14 26194078
2011 Catalytic mechanism of Sep-tRNA:Cys-tRNA synthase: sulfur transfer is mediated by disulfide and persulfide. The Journal of biological chemistry 14 22167197
2007 Quadruple or quintuple conversion of hlb, sak, sea (or sep), scn, and chp genes by bacteriophages in non-beta-hemolysin-producing bovine isolates of Staphylococcus aureus. Veterinary microbiology 14 17300883
2005 SEP-class genes in Populus tremuloides and their likely role in reproductive survival of poplar trees. Gene 14 16040208
2005 SELPLG and SELP single-nucleotide polymorphisms in multiple sclerosis. Neuroscience letters 14 16257118
2002 Molecular actions of (S)-desmethylzopiclone (SEP-174559), an anxiolytic metabolite of zopiclone. The Journal of pharmacology and experimental therapeutics 14 12130723
2023 Combined Platelet and Red Blood Cell Recovery during On-pump Cardiac Surgery Using same™ by i-SEP Autotransfusion Device: A First-in-human Noncomparative Study (i-TRANSEP Study). Anesthesiology 13 37294939
2022 Seizures, ataxia and parvalbumin-expressing interneurons respond to selenium supply in Selenop-deficient mice. Redox biology 13 36182809
2017 SEPP1 polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation. European journal of nutrition 13 28501922
2022 The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice. Molecules (Basel, Switzerland) 12 35566106
2021 Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway. Journal of oleo science 12 33840662
2018 The relationship between gestational diabetes mellitus and selenoprotein-P plasma 1 (SEPP1) gene polymorphisms. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 12 29648467
2018 Effects of selenium supplementation on expression of SEPP1 in mRNA and protein levels in subjects with and without metabolic syndrome suffering from coronary artery disease: Selenegene study a double-blind randomized controlled trial. Journal of cellular biochemistry 12 29932230
2016 P-Selectin Expressed by a Human SELP Transgene Is Atherogenic in Apolipoprotein E-Deficient Mice. Arteriosclerosis, thrombosis, and vascular biology 12 27102967
1989 A convenient, unified scheme for the differential extraction of conjugated and unconjugated serum C19 steroids on Sep-Pak C18-cartridges. Journal of steroid biochemistry 12 2770301
1983 24,25-dihydroxyvitamin D3 in serum: sample purification with Sep-Pak C-18 cartridges and liquid chromatography before protein-binding assay. Clinical chemistry 12 6604593
2023 Genome-wide analysis of MIKCC-type MADS-box genes and roles of CpFUL/SEP/AGL6 superclade in dormancy breaking and bud formation of Chimonanthus praecox. Plant physiology and biochemistry : PPB 11 36878163
2022 Lauric acid impairs insulin-induced Akt phosphorylation by upregulating SELENOP expression via HNF4α induction. American journal of physiology. Endocrinology and metabolism 11 35499234
2021 SELP Asp603Asn and severe thrombosis in COVID-19 males. Journal of hematology & oncology 11 34399825
2019 HMGB1 and SEPP1 as predictors of hepatocellular carcinoma in patients with viral C hepatitis: Effect of DAAs. Clinical biochemistry 11 31158358
2019 Relationship Between -2028 C/T SELP Gene Polymorphism, Concentration of Plasma P-Selectin and Risk of Malnutrition in Head and Neck Cancer Patients. Pathology oncology research : POR 10 30617759
2003 Trypsin/alpha-amylase inhibitors inactivate the endogenous barley/malt serine endoproteinase SEP-1. Journal of agricultural and food chemistry 10 12952437