Evidence map›Paper›PMID 39945068›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity.

Szumam Liu, Min Ma, Jun Qu, Joshua Muia, Zhijian Wu, Quintijn Bonnez, Karen Vanhoorelbeke, Liang Zheng, Xinyang Zhao, X Long Zheng

Abstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Szumam LiuDepartment of Pathology and Laboratory Medicine (S.L., Z.W., L.Z., X.Z., X.L.Z.), The University of Kansas Medical Center.ORCID 0000-0003-2643-5048
Min MaDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst (M.M., J.Q.).ORCID 0000-0002-4203-5215
Jun QuDepartment of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst (M.M., J.Q.).ORCID 0000-0002-1346-6809
Joshua MuiaThrombosis and Hemostasis Program, Versiti Blood Research Institute, Milwaukee, WI (J.M.).
Zhijian WuDepartment of Pathology and Laboratory Medicine (S.L., Z.W., L.Z., X.Z., X.L.Z.), The University of Kansas Medical Center.
Quintijn BonnezLaboratory for Thrombosis Research, Kortrijk, Belgium (Q.B., K.V.).ORCID 0000-0001-7209-530X
Karen VanhoorelbekeLaboratory for Thrombosis Research, Kortrijk, Belgium (Q.B., K.V.).
Liang ZhengDepartment of Pathology and Laboratory Medicine (S.L., Z.W., L.Z., X.Z., X.L.Z.), The University of Kansas Medical Center.
Xinyang ZhaoDepartment of Pathology and Laboratory Medicine (S.L., Z.W., L.Z., X.Z., X.L.Z.), The University of Kansas Medical Center.ORCID 0000-0001-6677-7072
X Long ZhengDepartment of Pathology and Laboratory Medicine (S.L., Z.W., L.Z., X.Z., X.L.Z.), The University of Kansas Medical Center.ORCID 0000-0003-1680-5295

Funding

Using Integrated Omics to Identify Dysfunctional Genetic Mechanisms Influencing Schizophrenia and Sleep DisturbancesP20GM130423 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Kalyani Pyaram, Steven Allan Soper · 2019 to 2026
$21.5M
Hematology Central Coordinating Center (HCCC) for the NIDDK Hematology Centers ProgramU24DK126127 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Anna E Beaudin, DEREK L STIREWALT · 2020 to 2026
$7.5M
Pathogenesis of thrombotic microangiopathiesR01HL164016 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI X. Long Zheng · 2023 to 2026
$2.1M
Investigating the regulation and substrate processing of ADAMTS13 and ADAMTS7 metalloproteases.R35GM142926 · NIGMS · VERSITI WISCONSIN, INC. · PI MUIA, JOSHUA MUTAMBUKI · 2021 to 2025
$2.0M
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic PurpuraR01HL144552 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHENG, X. LONG · 2019 to 2022
$1.8M
Mechanism underlying cofactor-dependent proteolysis of von Willebrand FactorR01HL157975 · NHLBI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ZHANG, XIAOHUI FRANK, ZHENG, X. LONG · 2022 to 2025
$1.8M
NHLBI NIH HHS R01 HL144552NHLBI NIH HHS R01 HL157975NHLBI NIH HHS R01 HL164016NIDDK NIH HHS U24 DK126127NIGMS NIH HHS P20 GM130423NIGMS NIH HHS R35 GM142926
6 · The paper itself

Abstract

backgroundADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, 13), primarily synthesized in hepatic stellate and endothelial cells, plays a pivotal role in regulation of hemostasis by proteolytic cleavage of von Willebrand factor. Severe deficiency of plasma ADAMTS13 activity may result in thrombotic thrombocytopenic purpura, a potentially fatal blood disorder. ADAMTS13 undergoes posttranslational modifications including glycosylation, citrullination, oxidation. The present study determines the impact of arginine methylation by PRMT1 (protein arginine methyltransferase 1) on ADAMTS13 secretion and function.

methodsCell culture, recombinant protein, biochemical analysis, site-directed mutagenesis, and animal models were utilized.

resultsAn inhibition of arginine methylation by a type I methyl transferase PRMT inhibitor (MS023) in HEK (human embryonic kidney) 293 cells expressing recombinant ADAMTS13 and in mice results in a significant reduction of ADAMTS13 secretion, but the secreted ADAMTS13 shows an increased specific activity; conversely, an overexpression of PRMT1 in HEK-293 cells and in transgenic mice results in an increase of ADAMTS13 secretion, but the secreted ADAMTS13 exhibits a significantly reduced specific activity. The altered ADAMTS13 activity appeared to be related to its conformational changes. LC-MS/MS (liquid chromatography with tandem mass spectrometry) identified greater than100 arginine methylation events on purified recombinant ADAMTS13. Site-directed mutagenesis performed on 5 highly conserved methylation sites (R193, R498, R692, R1123, and R1206) identifies the critical role of R1206 in ADAMTS13 function. The ADAMTS13 R1206K variant exhibits a 4- to 5-fold increase of specific activity, likely resulting from an alleviation of allosteric inhibition.

conclusionsThese results demonstrate the crucial role of arginine methylation in ADAMTS13 secretion and function. Our findings may shed new light on the mechanism of allosteric regulation of ADAMTS13, which may have a therapeutic implication.

Indexed as

ADAM ProteinsArginineProtein-Arginine N-MethyltransferasesRepressor ProteinsADAMTS13 ProteinAnimalsEnzyme InhibitorsHEK293 CellsHumansMethylationMiceMice, TransgenicMutagenesis, Site-DirectedProtein Processing, Post-TranslationalTransfectionADAM ProteinsADAMTS13 ProteinADAMTS13 protein, humanADAMTS13 protein, mouseArginineEnzyme InhibitorsPRMT1 protein, humanPrmt1 protein, mouseProtein-Arginine N-MethyltransferasesRepressor ProteinsADAMTS13animal modelarginine methylationthrombosis

Identifiers

PMID39945068
PMCPMC11945488

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.