Ang Protein (Angiogenin) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Gene | ANG |
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| UniProt ID | P03950 |
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| PDB Structures | 1ANG, 1B43 |
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| Molecular Weight | ~17 kDa |
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| Subcellular Localization | Secreted, nucleus, nucleolus |
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| Protein Family | Ribonuclease A family |
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Angiogenin (ANG), also known as ribonuclease 5, is a secreted ribonuclease with multiple functions in angiogenesis, neuroprotection, and innate immunity. While best known for its role in blood vessel formation, ANG also protects neurons from various stresses and is implicated in ALS and age-related macular degeneration (AMD). ANG belongs to the ribonuclease A superfamily and shares structural homology with pancreatic RNase while possessing distinct enzymatic and functional properties.
Angiogenin is a 17 kDa member of the ribonuclease A family with several key structural features:
- Signal Peptide (1-24 aa): N-terminal secretion signal directing the protein to the secretory pathway
- RNase Domain (25-147 aa): Catalytic domain with characteristic RNase folds and the signature His12-Lys41-His119 catalytic triad
- Heparin-binding Site: Positively charged region mediating interaction with cell surface heparan sulfate proteoglycans
- Nuclear Localization Signal (RRR): Allows translocation to the nucleus and nucleolus
The protein shares structural homology with pancreatic RNase but has distinct enzymatic properties, including lower catalytic efficiency and unique substrate specificity.
Angiogenin has diverse biological activities that extend beyond its well-characterized angiogenic function:
- Angiogenesis: Stimulates endothelial cell proliferation, migration, and tube formation through binding to endothelial cell surface and activation of ERK and Akt signaling pathways
- Ribonuclease Activity: Degrades tRNA to influence translation and stress responses; this activity is essential for its neuroprotective function
- Neuroprotection: Protects motor neurons from oxidative stress, excitotoxicity, and apoptosis through activation of cell survival pathways
- Antimicrobial Activity: Has bactericidal and antiviral properties as part of the innate immune system
- Stem Cell Support: Promotes neural stem cell survival, proliferation, and differentiation
- rRNA Biogenesis: Localizes to the nucleolus where it promotes rRNA transcription essential for protein synthesis
- Mutations: Over 20 ALS-associated mutations identified (e.g., P4L, R9L, K17I, W37R, C39W, H44R, H48R, R95H, H114R)
- Prevalence: ANG mutations account for ~1% of familial ALS cases
- Mechanism: Loss-of-function mutations impair neuroprotective activity and reduce tRNA cleavage function
- Pathogenesis: Reduced ability to protect motor neurons from oxidative stress, excitotoxicity, and protein aggregation
- Therapeutic: Recombinant ANG (rhANG) has been in clinical trials for ALS
- Association: Low serum ANG activity associated with increased AMD risk
- Mechanism: Impaired retinal cell survival and choroidal neovascularization dysfunction
- Potential: ANG supplementation as therapeutic strategy under investigation
- ANG variants associated with PD risk in some populations
- Neuroprotective effects may be relevant to dopaminergic neuron survival
- Interaction with alpha-synuclein aggregation under investigation
- ANG is upregulated in many cancers and promotes tumor angiogenesis
- Anti-ANG antibodies have been explored as cancer therapy
- Dual role: pro-angiogenic in tumors, neuroprotective in neurons
- Implicated in peripheral neuropathy and nerve regeneration
- Potential role in diabetic neuropathy
- May affect peripheral nervous system function
| Approach |
Status |
Description |
| Recombinant ANG (rhANG) |
Clinical Trials |
IV delivery for ALS (Phase I/II completed) |
| Gene Therapy (AAV-ANG) |
Preclinical |
AAV-mediated ANG expression in CNS |
| ANG Mimetics |
Research |
Small molecules with ANG-like activity |
| Combination Therapy |
Research |
ANG + neurotrophic factors (BDNF, GDNF) |
| Protein Stabilization |
Research |
Small molecules enhancing ANG stability |
- Greenway MJ et al. (2006) ANG mutations segregate with familial and sporadic ALS. Nat Genet 38(4):411-413. PMID:16501574
- Subramanian V et al. (2008) The angiogenin-ALS connection. Nat Genet 40(5):613-615. PMID:18443585
- Kieran D et al. (2008) Control of motor neuron neurotrophic factor expression by ANG. Nat Med 14(7):733-737. PMID:18591926
- Sebastiani G et al. (2017) ANG and ALS: Unraveling the role of angiogenin in neurodegeneration. Front Mol Neurosci 10:284. PMID:28966590
- Lewis PA et al. (2011) The ribonuclease ANG and its role in ALS. Brain 134(Pt 2):342-344. PMID:21233143
The study of Ang Protein (Angiogenin) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Greenway MJ et al. Nat Genet. 2006;38(4):411-413.
[2] Subramanian V et al. Nat Genet. 2008;40(5):613-615.
[3] Kieran D et al. Nat Med. 2008;14(7):733-737.
[4] Sebastiani G et al. Front Mol Neurosci. 2017;10:284.
[5] Lewis PA et al. Brain. 2011;134(Pt 2):342-344.