Endoglin Human
Description
Molecular Structure and Isoforms
Endoglin is a 180 kDa homodimeric type I transmembrane glycoprotein composed of disulfide-linked 95 kDa subunits . Key structural features include:
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Extracellular domain (561 aa): Contains an orphan domain for ligand binding (e.g., BMP-9) and a zona pellucida (ZP) domain for dimerization .
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Transmembrane domain: Anchors the protein to the cell membrane.
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Cytoplasmic tail (47 aa): Short and lacking enzymatic activity, serving as a modulator for signaling .
Two isoforms exist due to alternative splicing:
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L-endoglin (long isoform): Predominant form with a 47 aa cytoplasmic tail.
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S-endoglin (short isoform): Contains a 14 aa cytoplasmic tail and may antagonize L-endoglin .
Angiogenesis and Vascular Development
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Essential for embryonic vascular development: Endoglin knockout in mice causes embryonic lethality at E10.5 due to defective angiogenesis .
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Modulates TGF-β signaling by balancing ALK1 (pro-angiogenic) and ALK5 (anti-angiogenic) pathways .
Beyond Endothelial Cells
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Expressed on activated monocytes, fibroblasts, and cancer-associated stromal cells .
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Regulates immune responses and fibrosis in pathological conditions .
Hereditary Hemorrhagic Telangiectasia (HHT)
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HHT Type 1: Caused by mutations in the ENG gene (chromosome 9q34.11), leading to vascular malformations and recurrent bleeding .
Preeclampsia
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Elevated soluble endoglin (sENG) levels disrupt vascular homeostasis by antagonizing TGF-β and integrin signaling, contributing to endothelial dysfunction .
Cancer
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Tumor Angiogenesis: Highly expressed in tumor vasculature, making it a target for anti-angiogenic therapies .
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Paradoxical Role: While promoting angiogenesis, reduced membrane-bound endoglin in breast cancer correlates with metastasis .
Signaling Mechanisms
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TGF-β/ALK1 Pathway: Endoglin enhances BMP-9/ALK1 signaling, promoting endothelial proliferation .
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ALK5 Inhibition: Reduces TGF-β-induced growth inhibition in endothelial cells .
Soluble Endoglin (sENG)
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Generated via MMP-14 cleavage, sENG acts as a decoy receptor, disrupting BMP-9 signaling and platelet adhesion .
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Monomeric sENG dominates in preeclampsia plasma, exacerbating vascular dysfunction .
Therapeutic Targeting
Expression Profile
Recombinant Endoglin in Research
Product Specs
Product Science Overview
Endoglin is a 90 kDa protein that forms a disulfide-linked homodimer on the cell surface . It associates with TGF-β type I receptors, including the endothelial cell-specific ALK1 (activin receptor-like kinase 1) and the ubiquitous ALK5, as well as the TGF-β type II receptor . This association is essential for the regulation of angiogenesis and vascular development.
Mutations in the endoglin gene are responsible for Hereditary Hemorrhagic Telangiectasia (HHT) type 1, a vascular disorder characterized by defective angiogenesis, arteriovenous malformations, telangiectasia, and frequent nosebleeds (epistaxis) . Additionally, endoglin is implicated in preeclampsia, a pregnancy-related condition characterized by high blood pressure and damage to other organ systems .
Recombinant human endoglin is produced using a mouse myeloma cell line, NS0-derived human endoglin/CD105 protein . It is typically used in research to study its role in angiogenesis and related diseases. The recombinant protein is purified to a high degree, with a purity greater than 90% as determined by SDS-PAGE . It is also tested for endotoxin levels to ensure it is suitable for use in various biological assays .
Recombinant human endoglin is used in various research applications, including:
- Studying TGF-β signaling pathways: As a co-receptor for TGF-β ligands, endoglin is crucial for understanding the signaling mechanisms involved in angiogenesis and vascular development.
- Investigating vascular diseases: Research on endoglin helps in understanding the molecular basis of diseases like HHT and preeclampsia.
- Drug development: Endoglin is a potential therapeutic target for diseases involving abnormal blood vessel formation.
