ArticlePloS one2012
Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 31 papers.
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.
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.
Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Human Epididymis Protein 4 in Cardiovascular Disease: A Fibrosis-Driven Mediator of Tissue Remodeling and Inter-Organ Communication.Circulation reports · 2026Review
- The level of human epididymis protein 4 is associated with poor prognosis in patients with ejection fraction preserved heart failure.Frontiers in cardiovascular medicine · 2025Article
- HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.European journal of medical research · 2024Article
- Retraction: Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor.PloS one · 2024Article
- Prognostic Value of Human Epididymis Protein 4 in Acute Myocardial Infarction.International journal of general medicine · 2024Article
- HE4 Serum Levels are Associated with Poor Prognosis in Patients with Acute Heart Failure Combined with Chronic Kidney Disease.International journal of general medicine · 2024Article
- Versatile whey acidic protein four-disulfide core domain proteins: biology and role in diseases.Frontiers in cell and developmental biology · 2024Review
- Evaluation of He4 Use in the Diagnosis of Ovarian Cancer: First and Second Recurrence, and an Analysis of HE4 Concentration during Second- and Third-Line Chemotherapy.Diagnostics (Basel, Switzerland) · 2023Article
- Article
- Roles of Antimicrobial Peptides in Gynecological Cancers.International journal of molecular sciences · 2022Review
- Human epididymis protein 4 (HE4) is a novel biomarker for fibrosis in IgG4-related disease and can predict poor prognosis.RMD open · 2022Article
- A bioinformatic analysis of WFDC2 (HE4) expression in high grade serous ovarian cancer reveals tumor-specific changes in metabolic and extracellular matrix gene expression.Medical oncology (Northwood, London, England) · 2022Article
- Article
- Serum Human Epididymis Protein 4 is a Potential Biomarker for Early Chronic Kidney Disease in an Obese Population.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- WFDC Protein: A Promising Diagnosis Biomarker of Ovarian Cancer.Journal of Cancer · 2021Review
- New Insights in Laboratory Testing for COVID-19 Patients: Looking for the Role and Predictive Value ofMicroorganisms · 2020Article
- Ulcerative colitis: Recent advances in the understanding of disease pathogenesis.F1000Research · 2020Review
- Hypoxia-Induced Upregulation of HE4 Is Responsible for Resistance to Radiation Therapy of Gastric Cancer.Molecular therapy oncolytics · 2019Article
- Stable-protein Pair Analysis as A Novel Strategy to Identify Proteomic Signatures: Application To Seminal Plasma From Infertile Patients.Molecular & cellular proteomics : MCP · 2019Article
- Article
Corrections and comments
- Retraction · 2024-06-11Concerns/Issues about Image · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Objections by Author(s) · Unreliable Data ·
- Retracted
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epididymal proteins represent the factors necessary for maturation of sperm and play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member of whey acidic protein four-disulfide core (WFDC) family with no known function. A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains. Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide-bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate. Using SPR we have also observed that HE-4 shows a significant binding with all these proteases. Disulfide linkages are essential for this activity. Moreover, HE-4 is N-glycosylated and highly stable on a wide range of pH and temperature. Taken together this suggests that HE-4 is a cross-class protease inhibitor which might confer protection against microbial virulence factors of proteolytic nature.
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What OpenQuestion holds
Registered trials
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.