ANGPT1 Human
Description
Gene Structure and Protein Characteristics
The ANGPT1 gene (ENSG00000154188) is located on chromosome 8q23.1 and spans 8 transcripts, including canonical and alternative splice variants . Key features include:
| Property | Details |
|---|---|
| Gene ID | ENSG00000154188 |
| Protein Length | 498 amino acids (canonical isoform) |
| Domains | N-terminal coiled-coil, C-terminal fibrinogen-like domain |
| Expression | Pericytes, stromal cells, and mesenchymal tissues |
| Orthologs | 223 species, including mouse and porcine models |
The canonical transcript (ENST00000517746.6) encodes a secreted protein with a signal peptide and heparin-binding motifs critical for receptor activation .
Biological Functions
ANGPT1 primarily regulates vascular integrity through TEK/TIE2 signaling.
Key Mechanisms
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Vascular Stabilization
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Angiogenesis Control
Critical Interactions
ANGPT1 binds TEK/TIE2 with high affinity, inducing receptor dimerization and tyrosine phosphorylation . Other interactors include:
| Protein | Role | Interaction Score |
|---|---|---|
| TEK/TIE2 | Primary receptor for ANGPT1 signaling | 0.999 |
| TIE1 | Modulates TEK/TIE2 activity, enhances survival signaling | 0.998 |
| VEGFR2 (KDR) | Cross-talk with VEGF pathways in angiogenesis | 0.994 |
Developmental Roles
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Embryonic Vascularization: Angpt1 knockout mice exhibit lethal defects in heart and vascular development by E12.5 .
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Ocular Vasculature: Neural crest-specific Angpt1 deletion disrupts choriocapillaris and vortex vein formation, mirroring human pachychoroid diseases .
Disease Associations
Cancer Biology Insights
ANGPT1 exhibits context-dependent roles in tumorigenesis:
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Tumor Suppression: In endometrial carcinoma, low ANGPT1 expression associates with favorable outcomes and reduced immune infiltration (e.g., Tregs) .
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Tumor Progression: In breast cancer, high ANGPT1 promotes angiogenesis and metastasis .
Tissue-Specific Expression
Detection Methods
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Antibodies: Mouse anti-human ANGPT1 (e.g., R&D Systems MAB923) for IHC/Western blot .
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qPCR Primers: NM_001146-specific primers for RNA analysis (Origene HP205085) .
Recombinant Proteins
R&D Systems’ recombinant human ANGPT1 (923-AN-025) is validated for bioactivity assays, including endothelial cell survival and migration studies .
Future Directions
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Therapeutic Targeting:
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ANGPT1 agonists for diabetic retinopathy or ischemic diseases.
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ANGPT1 antagonists for cancers with high angiopoietin signaling.
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Biomarker Development:
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ANGPT1/ANGPT2 ratio as a diagnostic marker for preeclampsia or pachychoroid diseases.
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Product Specs
Product Science Overview
Angiopoietin-1 contains a coiled-coil region and a C-terminal fibrinogen-like domain separated by a short flexible region . This structure allows it to interact with its receptor, Tie-2, a cell surface receptor tyrosine kinase expressed in endothelial and hemopoietic cells . The binding of Ang-1 to Tie-2 activates signaling pathways that promote blood vessel maturation and stability .
Angiopoietin-1 is essential for the proper development of the vascular system during embryogenesis. It helps in the maturation and stabilization of blood vessels by promoting the interaction between endothelial cells and surrounding support cells . This interaction is critical for maintaining the integrity and functionality of the vascular network.
Recombinant human Angiopoietin-1 (rHuANG-1) has been developed for research and potential therapeutic applications. It is produced using recombinant DNA technology, where the gene encoding Ang-1 is inserted into a host cell, typically a mouse myeloma cell line, to produce the protein . The recombinant protein is then purified and used in various studies to understand its role in vascular biology and its potential therapeutic benefits.
Studies have shown that Angiopoietin-1 can inhibit serum deprivation-induced apoptosis in human umbilical vein endothelial cells (HUVECs), indicating its protective role in vascular cells . This property makes it a potential candidate for therapeutic applications in diseases involving vascular dysfunction, such as diabetic retinopathy, atherosclerosis, and cancer .
Recombinant human Angiopoietin-1 is typically lyophilized from a filtered solution and can be reconstituted in sterile PBS containing human or bovine serum albumin . It is stable for up to 12 months when stored at -20 to -70°C and should be handled under sterile conditions to maintain its activity .
