ArticleThe Journal of biological chemistry2020
Proteomics-based screening of the endothelial heparan sulfate interactome reveals that C-type lectin 14a (CLEC14A) is a heparin-binding protein.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- CLEC14A correlates with neutrophil infiltration in hepatocellular carcinoma and mediates neutrophil recruitment across liver endothelial cells.The Journal of pathology · 2026Article
- CLEC18A interacts with sulfated glycosaminoglycans and controls clear cell renal cell carcinoma progression.The FEBS journal · 2026Article
- A guide to building the matrisome interactome: from computational predictions to experimental validation.The FEBS journal · 2026Review
- Proteoglycans and glycosaminoglycans: critical regulators in angiogenesis, vasculogenesis, and vascularized tissue engineering.Angiogenesis · 2025Review
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Interactions of proteins with heparan sulfate.Essays in biochemistry · 2024Review
- Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.Essays in biochemistry · 2024Review
- Development of a Proteomic Workflow for the Identification of Heparan Sulphate Proteoglycan-Binding Substrates of ADAM17.Proteomics · 2024Article
- Heparin-enriched plasma proteome is significantly altered in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Alteration of Neuropilin-1 and Heparan Sulfate Interaction Impairs Murine B16 Tumor Growth.ACS chemical biology · 2024Article
- The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis.Cellular and molecular life sciences : CMLS · 2024Article
- Multivalent, calcium-independent binding of surfactant protein A and D to sulfated glycosaminoglycans of the alveolar epithelial glycocalyx.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Strategies for Mitigating Commercial Sensor Chip Variability with Experimental Design Controls.Sensors (Basel, Switzerland) · 2023Article
- Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.Cellular and molecular neurobiology · 2023Review
- Application of the Nicoya OpenSPR to Studies of Biomolecular Binding: A Review of the Literature from 2016 to 2022.Sensors (Basel, Switzerland) · 2023Review
- Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- (Glycan Binding) Activity-Based Protein Profiling in Cells Enabled by Mass Spectrometry-Based Proteomics.Israel journal of chemistry · 2023Article
- MS-proteomics provides insight into the host responses towards alginate microspheres.Materials today. Bio · 2022Article
- Excavating proteoglycan structure-function relationships: modern approaches to capture the interactions of ancient biomolecules.American journal of physiology. Cell physiology · 2022Review
- Molecular dynamics simulations to understand glycosaminoglycan interactions in the free- and protein-bound states.Current opinion in structural biology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Animal cells express heparan sulfate proteoglycans that perform many important cellular functions by way of heparan sulfate-protein interactions. The identification of membrane heparan sulfate-binding proteins is challenging because of their low abundance and the need for extensive enrichment. Here, we report a proteomics workflow for the identification and characterization of membrane-anchored and extracellular proteins that bind heparan sulfate. The technique is based on limited proteolysis of live cells in the absence of denaturation and fixation, heparin-affinity chromatography, and high-resolution LC-MS/MS, and we designate it LPHAMS. Application of LPHAMS to U937 monocytic and primary murine and human endothelial cells identified 55 plasma membrane, extracellular matrix, and soluble secreted proteins, including many previously unidentified heparin-binding proteins. The method also facilitated the mapping of the heparin-binding domains, making it possible to predict the location of the heparin-binding site. To validate the discovery feature of LPHAMS, we characterized one of the newly-discovered heparin-binding proteins, C-type lectin 14a (CLEC14A), a member of the C-type lectin family that modulates angiogenesis. We found that the C-type lectin domain of CLEC14A binds one-to-one to heparin with nanomolar affinity, and using molecular modeling and mutagenesis, we mapped its heparin-binding site. CLEC14A physically interacted with other glycosaminoglycans, including endothelial heparan sulfate and chondroitin sulfate E, but not with neutral or sialylated oligosaccharides. The LPHAMS technique should be applicable to other cells and glycans and provides a way to expand the repertoire of glycan-binding proteins for further study.
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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.