| SYNE1 Protein | |
|---|---|
| Gene | [SYNE1](/genes/syne1) (ENSG00000105669) |
| UniProt ID | [Q8NF91](https://www.uniprot.org/uniprot/Q8NF91) |
| Alternative Names | Nesprin-1, Myocyte Enhancer Factor 2C, Enaptin |
| Molecular Weight | 1,001,000 Da (full-length isoform) |
| Subcellular Localization | Nuclear envelope, outer nuclear membrane, cytoplasmic |
| Protein Family | Spectrin repeat family, Nesprin family |
| PDB Structures | 6GXX, 7B7H (KASH domain) |
SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1), also known as Nesprin-1, is a massive (~1 MDa) scaffold protein that connects the nuclear envelope to the actin cytoskeleton. It plays critical roles in nuclear positioning, cellular migration, and mechanotransduction. SYNE1 mutations cause autosomal recessive cerebellar ataxia type 1 (SCAR8/ARCA1) and have been implicated in various neurodegenerative diseases[1].
SYNE1 is one of the largest human proteins, with multiple structural domains:
The protein forms homodimers and interacts with other nesprins, SUN proteins, and nuclear envelope components to form the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex[2].
In the nervous system, SYNE1 is essential for:
Biallelic SYNE1 mutations cause autosomal recessive cerebellar ataxia type 1, characterized by:
Current therapeutic approaches targeting SYNE1-related pathways include:
No SYNE1-targeted drugs are currently in clinical trials, but the protein represents a promising target for ataxia and neurodegeneration[5].
Zhang et al., SYNE1 mutations cause autosomal recessive cerebellar ataxia (2007). American Journal of Human Genetics.
Crisp et al., LINC complex mechanotransduction (2015). Trends in Cell Biology.
Synofzik et al., SYNE1 ataxia: phenotype and genotype (2016). Neurology.
Global Alliance for Genomics and Health, SYNE1 in neurodegeneration (2021). Nature Genetics.
Janer et al., SYNE1 deficiency causes cerebellar atrophy (2012). Brain.
Gros-Louis et al. Mutations in SYNE1 cause autosomal recessive cerebellar ataxia. Nature Genetics. 2010. ↩︎
Starr & Han. Role of ANC-1 in nuclear positioning. Trends in Cell Biology. 2003. ↩︎
Synofzik et al. Phenotypic spectrum of SYNE1-related ataxia. Neurology. 2016. ↩︎
Ferrari et al. Genome-wide association study of Alzheimer's disease. JAMA Psychiatry. 2014. ↩︎
Horn. Therapeutic targeting of the LINC complex. Trends in Pharmacological Sciences. 2019. ↩︎