| SNX3 — Sorting Nexin 3 | |
|---|---|
| Phosphoinositide-Binding Retromer Component | |
| Gene Symbol | SNX3 |
| Protein | SNX3 Protein |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 8724 |
| Ensembl ID | ENSG00000128967 |
| OMIM ID | 604767 |
| UniProt ID | O60443 |
| Aliases | Mvp1, SDU1 |
| Associated Diseases | Parkinson's Disease, Alzheimer's Disease, Neurodegeneration |
SNX3 (Sorting Nexin 3) is a member of the sorting nexin family of phosphoinositide-binding proteins involved in endosomal trafficking and membrane protein sorting[1]. SNX3 functions as a key component of the retromer complex, playing crucial roles in intracellular protein trafficking. Unlike many sorting nexins, SNX3 lacks a PX domain and instead uses a proprietary binding interface to recognize phosphoinositides on endosomal membranes[2].
SNX3 is a peripheral membrane protein that localizes to early endosomes and functions in several key capacities:
SNX3 forms part of the cargo-selective complex (CSC) of the retromer that recognizes transmembrane cargo proteins:
SNX3 plays a critical role in iron homeostasis[3]:
SNX3 dysfunction contributes to multiple neurodegenerative diseases through endosomal trafficking impairments[4]:
SNX3 plays a significant role in Parkinson's disease pathogenesis[5]:
SNX3 in AD[6]:
The neurodegenerative mechanisms involving SNX3 include:
Targeting SNX3 and the retromer pathway represents a therapeutic strategy for neurodegenerative diseases[7]:
| Protein | Interaction Type |
|---|---|
| VPS26 | Retromer complex |
| VPS29 | Retromer complex |
| VPS35 | Retromer complex |
| LRRK2 | Kinase interaction |
| TFRC | Cargo trafficking |
| DMT1 | Iron transporter |
Sorting nexin 3 (SNX3) is required for endosomal sorting of the copper transporter ATP7B. Molecular Biology of the Cell. 2013. ↩︎
Structure and function of SNX3 in retromer-mediated trafficking. Journal of Cell Science. 2016. ↩︎
SNX3 regulates iron homeostasis through retromer-dependent trafficking. Blood. 2015. ↩︎
Endosomal trafficking defects in neurodegenerative disease. Nature Reviews Neuroscience. 2019. ↩︎
SNX3 variants in familial Parkinson's disease. Movement Disorders. 2018. ↩︎
SNX3 and APP trafficking in Alzheimer's disease. Journal of Alzheimer's Disease. 2017. ↩︎
Retromer stabilization as a therapeutic strategy for neurodegenerative disorders. Neurobiology of Disease. 2021. ↩︎