Evidence map›Paper›PMID 24828501›Full record

ArticleThe Journal of biological chemistry2014

Corin mutations K317E and S472G from preeclamptic patients alter zymogen activation and cell surface targeting. [Corrected].

Ningzheng Dong, Tiantian Zhou, Yue Zhang, Meng Liu, Hui Li, Xiaoyi Huang, Zhenzhen Liu, Yi Wu, Koichi Fukuda, Jun Qin and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.9field-weighted citation impact, top 7% of its field
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

35 citing papers in PubMed, 51 citations in OpenAlex.

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  11. Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  12. Review
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  14. N-Glycan-calnexin interactions in human factor VII secretion and deficiency.The international journal of biochemistry & cell biology · 2019
    Article
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Ningzheng DongFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, and Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China.
Tiantian ZhouFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease.
Yue ZhangFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease.
Meng LiuFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease.
Hui LiFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease.
Xiaoyi Huangthe International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, China, and.
Zhenzhen LiuFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease.
Yi WuFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China.
Koichi FukudaMolecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195.
Jun QinMolecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195.
Qingyu WuFrom the Cyrus Tang Hematology Center and MOE Engineering Center of Hematological Disease, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, China, Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195 wuq@ccf.org.
Cleveland Clinic Lerner College of Medicine · USSoochow University · CNInternational Peace Maternity & Child Health Hospital · CN

Funding

The cardiac protease corin in natriuretic peptide processing and hypertensionR01HL089298 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI WU, QINGYU · 2008 to 2012
$2.2M
Serine Protease Corin in Pregnancy-induced HypertensionR01HD064634 · NICHD · CLEVELAND CLINIC LERNER COM-CWRU · PI WU, QINGYU · 2011 to 2015
$1.6M
NHLBI NIH HHS HL089298NHLBI NIH HHS R01 HL089298NICHD NIH HHS HD064634NICHD NIH HHS R01 HD064634
6 · The paper itself

Abstract

Corin is a membrane-bound serine protease that acts as the atrial natriuretic peptide (ANP) convertase in the heart. Recent studies show that corin also activates ANP in the pregnant uterus to promote spiral artery remodeling and prevent pregnancy-induced hypertension. Two CORIN gene mutations, K317E and S472G, were identified in preeclamptic patients and shown to have reduced activity in vitro. In this study, we carried out molecular modeling and biochemical experiments to understand how these mutations impair corin function. By molecular modeling, the mutation K317E was predicted to alter corin LDL receptor-2 module conformation. Western blot analysis of K317E mutant in HEK293 cells showed that the mutation did not block corin expression on the cell surface but inhibited corin zymogen activation. In contrast, the mutation S472G was predicted to abolish a β-sheet critical for corin frizzled-2 module structure. In Western blot analysis and flow cytometry, S472G mutant was not detected on the cell surface in transfected HEK293 cells. By immunostaining, the S472G mutant was found in the ER, indicating that the mutation S472G disrupted the β-sheet, causing corin misfolding and ER retention. Thus, these results show that mutations in the CORIN gene may impair corin function by entirely different mechanisms. Together, our data provide important insights into the molecular basis underlying corin mutations that may contribute to preeclampsia in patients.

Indexed as

Mutation, MissenseAmino Acid SubstitutionEnzyme ActivationEnzyme PrecursorsFemaleFrizzled ReceptorsHEK293 CellsHumansLow Density Lipoprotein Receptor-Related Protein-2Pre-EclampsiaPregnancyProtein Structure, SecondarySerine EndopeptidasesCORIN protein, humanEnzyme PrecursorsFrizzled ReceptorsFZD2 protein, humanLow Density Lipoprotein Receptor-Related Protein-2Serine Endopeptidasescoringenetic diseasegenetic polymorphismhypertensionmembrane proteinnatriuretic peptidepreeclampsiapregnancyproteaseproteolytic enzyme

Identifiers

PMID24828501
PMCPMC4067221
OpenAlexW2098230066

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.