Get4 Gene 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 |
|---|---|
| Gene Symbol | GET4 |
| Full Name | GET4 (Guided Entry of Tail-anchored protein 4) |
| Chromosomal Location | 7q32.1 |
| NCBI Gene ID | 612197 |
| OMIM | 612197 |
| Ensembl ID | ENSG00000156958 |
| UniProt ID | Q9Y3D8 |
| Associated Diseases | Alzheimer's Disease, Protein Misfolding Disorders |
GET4 is involved in targeting tail-anchored proteins to the endoplasmic reticulum and plays a role in protein quality control. Recent studies suggest GET4 may be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative conditions through its interactions with ERAD components and protein aggregation pathways.
The GET4 gene encodes a protein that plays important roles in cellular homeostasis, protein quality control, and signal transduction. Understanding its normal function provides insight into how dysregulation contributes to disease.
This gene is expressed in various brain regions with particular enrichment in areas affected in neurodegenerative diseases:
The GET4 gene has been implicated in Alzheimer's Disease through genetic association studies and functional analyses. Variants may affect protein function or expression, leading to altered cellular phenotypes.
Research is ongoing to develop therapeutic strategies targeting GET4 pathways:
The study of Get4 Gene 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 GET4 gene spans approximately 15 kb of genomic DNA on chromosome 7q32.1 and consists of 8 exons. The protein product is 336 amino acids with a molecular weight of approximately 37 kDa. GET4 is evolutionarily conserved across eukaryotes, with orthologs in yeast (Get4p), C. elegans, Drosophila, and mammals, suggesting an essential cellular function.
GET4 contains several functional domains:
GET4 forms a heterodimeric complex with CALU (Calumenin), which together facilitate the targeting of tail-anchored proteins to the endoplasmic reticulum. This complex works in conjunction with the GET (Guided Entry of Tail-anchored proteins) pathway components including GET1, GET2, and GET3 (Asna1/TRC40).
| Protein | Interaction Type | Functional Significance |
|---|---|---|
| CALU | Direct binding | Co-chaperone for TA protein targeting |
| GET3/TRC40 | Substrate delivery | ATP-dependent TA protein insertion |
| GET1/GET2 | ER membrane | Channel for membrane insertion |
| BiP | ER chaperone | Folding and quality control |
GET4 knockout mice show embryonic lethality, indicating an essential role in development. Conditional knockout studies in neurons demonstrate:
Zebrafish models of GET4 deficiency show developmental defects in neural tube formation, providing insights into its role in neurodevelopment.
While GET4 is not a causative gene for familial neurodegenerative diseases, variants may act as disease modifiers:
GET4 levels in cerebrospinal fluid (CSF) are being investigated as a biomarker for: