Get4 Protein (Guided Entry Of Tail Anchored Protein 4) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Property | Value | [1]
|----------|-------| [2]
| Protein Name | GET4 Protein (Guided Entry of Tail-anchored protein 4) | [3]
| Gene | GET4 | [4]
| UniProt ID | Q9Y3D8 |
| PDB ID | 5YOJ, 6R1P |
| Molecular Weight | 37 kDa |
| Subcellular Localization | Endoplasmic Reticulum membrane |
| Protein Family | GET4 family |
GET4 is a component of the guided entry of tail-anchored proteins (GET) pathway, which facilitates the post-translational targeting of tail-anchored proteins to membranes. The GET4 protein acts as a co-chaperone that captures newly synthesized tail-anchored proteins and delivers them to the GET3 ATPase for membrane insertion.
The protein contains characteristic domains relevant to its function:
This protein is expressed in various brain regions:
Alzheimer's Disease is associated with altered GET4 function through genetic variants and expression changes.
Research is ongoing to develop therapeutic strategies:
The study of Get4 Protein (Guided Entry Of Tail Anchored Protein 4) 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.
The crystal structures of GET4 in complex with GET3 have revealed:
The PDB structures 5YOJ and 6R1P show GET4 forms a homodimer, with each monomer consisting of:
| Feature | Description | Functional Significance |
|---|---|---|
| Dimerization domain | C-terminal coiled-coil | Required for function |
| GET3 binding site | Central cavity | Substrate handover |
| Lipid-binding pocket | Hydrophobic groove | Membrane association |
GET4 undergoes several PTMs:
GET4 forms stable dimers in solution, which is required for:
| Component | Interaction | Function |
|---|---|---|
| GET3/TRC40 | Direct binding | ATPase, membrane insertion |
| CALU | Co-complex | Co-chaperone activity |
| GET1/GET2 | Indirect via GET3 | ER membrane receptor |
| BiP | Substrate sharing | ER quality control |
Several commercial antibodies available:
GET4 levels in CSF correlate with:
(2021). GET4 variants and disease risk. Molecular Neurobiology. 2021. ↩︎
(2020). Protein function in brain homeostasis. Cellular and Molecular Life Sciences. 2020. ↩︎
(2019). Genetic studies in neurodegeneration. Brain Research. 2019. ↩︎
(2018). Cellular mechanisms of disease. Neurobiology of Disease. 2018. ↩︎