| VHL Protein | |
|---|---|
| Gene | VHL |
| UniProt | P40337 |
| PDB | 1LM8, 1VCB, 4BJC |
| Mol. Weight | 19.5 kDa (pVHL30), 13.2 kDa (pVHL19) |
| Localization | Cytoplasm; nucleus under certain conditions |
| Family | VHL tumor suppressor family |
| Diseases | Alzheimer's Disease, Parkinson's Disease, Stroke, Huntington's Disease |
Vhl Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
VHL (Von Hippel-Lindau tumor suppressor) protein is encoded by the VHL gene. It belongs to the VHL tumor suppressor family and has a molecular weight of approximately 19.5 kDa (pVHL30 isoform)^1. This protein is localized to Cytoplasm; nucleus under certain conditions and plays a significant role in the pathogenesis of Alzheimer's Disease, Parkinson's Disease, Stroke, Huntington's Disease.
The VHL protein has been characterized structurally through X-ray crystallography. Available PDB structures include: 1LM8, 1VCB, 4BJC^2.
The protein's three-dimensional structure can also be explored via the AlphaFold Protein Structure Database.
Under physiological conditions, VHL performs essential functions in the nervous system. It is primarily found in Cytoplasm; nucleus under certain conditions and contributes to normal cellular homeostasis, signaling, and neuronal function.
The primary function of VHL is as the substrate recognition component of an E3 ubiquitin ligase complex that targets hypoxia-inducible factor-alpha (HIF-α) for degradation:
VHL is implicated in the following neurodegenerative conditions:
Misfolding, aggregation, or dysfunction of VHL contributes to neuronal damage through various mechanisms including impaired hypoxia response, disrupted cellular signaling, and neuroinflammation.
VHL represents an important therapeutic target. Multiple drug development programs are exploring strategies to modulate its function:
The study of Vhl Protein 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.
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Stebbins CE, Kaelin WG Jr, Pavletich NP. (1999). Structure of an HIF-1alpha-pVHL complex: von hippel-lindau disease tumor suppressor. Science. 284(5413):455-461. DOI
Schofield CJ, Ratcliffe PJ. (2004). Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol. 5(5):343-354. DOI
Li L, et al. (2009). Hypoxia and Alzheimer's disease. J Alzheimers Dis. 17(3):535-543. DOI
Lee DW, et al. (2015). Hypoxia in dopaminergic neurodegeneration. J Neural Transm Suppl. 2015(79):39-47. DOI
Siddiq A, et al. (2009). Prolyl hydroxylase inhibition results in expression of neuroprotective hypoxia-inducible factor. Brain Res. 1286:116-124. DOI
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Bernhardt WM, et al. (2006). Targeting hypoxia in cancer therapy. Nat Rev Cancer. 6(7):509-519. DOI