Function
Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenenis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.
Gene References into Functions
- The functional integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity and the inside-out mechanical coupling that tunes the cell internal stiffness to match that of its soft, physiological-like environment. PMID: 28455503
- Authors screened 937 BPD samples for genetic variation in SYNE1 exons 14-33, which covers the CPG2 region, using high-resolution melt analysis. Nine patients are compound heterozygotes for variants in SYNE1/CPG2, suggesting that rare coding variants may contribute significantly towards the complex genetic architecture underlying BPD. PMID: 28178086
- The frequency of CACNA1C rs10848683 in genetic high-risk individuals was double that in controls. For SYNE1 rs214950, higher frequencies were found in the genetic high-risk group than in controls. Polymorphisms in CACNA1C and SYNE1 could confer a greater risk of developing Schizophrenia and Bipolar Disorder in individuals who are already at high risk because of their family history. PMID: 27620326
- three novel rare variants (R8272Q, S8381C and N8406K) in the C-terminus of the SYNE1 gene (nesprin-1) were identified in seven dilated cardiomyopathy patients by mutation screening. Expression of these mutants caused nuclear morphology defects and reduced lamin A/C and SUN2 staining at the Nuclear envelope. PMID: 28398466
- We reported a novel mutation in exon 46 on codon 2304 (G2304R) of the SYNE1 gene in a Chinese family with Emery-Dreifuss muscular dystrophy-like features, and 100 healthy individuals did not show such mutation. PMID: 28583108
- Nonsense mutation in the ultimate exon of full-length SYNE1 causes congenital onset of muscular weakness with distal arthrogryposis. PMID: 27782104
- The results show that nesprin-1-alpha2 is dynamically controlled and may be involved in some process occurring during early myofibre formation, such as re-positioning of nuclei. PMID: 27350129
- findings revise the view that SYNE1 ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec. Instead, complex phenotypes with a wide range of extra-cerebellar neurological and nonneurological dysfunctions are frequent, including in particular motor neuron and brainstem dysfunction. PMID: 27086870
- This study demonstrate four novel truncating mutations in SYNE1 in pedigrees from British, Sri Lankan and Turkish origin in patient with cerebellar ataxia. PMID: 27178001
- A full length transcript homologous to rat CPG2 exists within human SYNE1. A full length transcript homologous to rat CPG2 exists within human SYNE1. PMID: 26704904
- SNP rs79575945 in ESR1 gene is associated with cancers of endometrioid subtype and resulted in the expression of SYNE1. PMID: 26330482
- Mechanostimulation mediates nuclear changes in oligodendrocyte progenitor cells via the SYNE1 complex. PMID: 26791211
- our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection. PMID: 25538088
- Drosophila melanogaster larval muscles, exhibiting both elastic features contributed by the stretching capacity of MSP300 (nesprin) and rigidity provided by a perinuclear network of microtubules stabilized by Shot (spectraplakin) and EB1. PMID: 26008743
- ur results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with menstrual migraine. PMID: 25315199
- A report of a family with a SYNE1 gene mutation that seems to cause an "Emery-Dreifuss muscular dystrophy-like" phenotype. PMID: 25091525
- a role for Nesprin-1 in the DNA damage response pathway PMID: 24781983
- FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. PMID: 24280874
- These data identify p50(Nesp1) as a multi-functional P-body component and microtubule scaffold necessary for RNA granule dynamics and provides evidence for P-body and stress granule micro-heterogeneity. PMID: 24862572
- role of CSMD1 and SYNE1 in the etiology of bipolar disorder PMID: 24387768
- Two novel truncating mutations were found among the French-Canadian participants, and 2 other novel mutations were found in a patient from France and a patient from Brazil. PMID: 23959263
- The findings of this study add to the evidence that association of SYNE1 mutation influences susceptibility to bipolar and unipolar mood disorders. PMID: 22565781
- we report 4 novel homozygous SYNE1 mutations in 3 Japanese patients with cerebellar ataxia PMID: 23325900
- These results indicate that nesprin-1 knockdown releases the nucleus from the tension of F-actin bound to the nucleus, thereby increasing allowance for deformation before stretching, and that F-actin bound to the nucleus through nesprin-1 causes sustainable force transmission to the nucleus. PMID: 22728879
- analysis of nsprin-1 mutations in human and murine cardiomyopathy PMID: 19944109
- Nesprin-1 depletion increased the number of focal adhesions and substrate traction while decreasing the speed of cell migration PMID: 20655839
- a single nucleotide polymorphism downstream of ESR1, a gene called spectrin repeat containing, nuclear envelope 1, was associated with invasive ovarian cancer risk PMID: 20056644
- Vertebrate Nesprin-1 and nesprin-2 proteins are orthologous to Drosophila melanogaster muscle protein MSP-300 PMID: 12408964
- The role of Syne-1 in cytokinesis involves an interaction with kinesin II. PMID: 14709720
- Enaptin is an element of the nuclear membrane and the actin cytoskeleton. PMID: 15093733
- The Nesprin-1 is essential for the interaction with a C-terminal region in SUN1 protein. PMID: 16079285
- These findings indicate that GSRP-56 is a small Golgi-localized splice-isoform of the spectrin-repeat-containing Syne1 gene. PMID: 16875688
- SYNE1 is the first identified gene responsible for a recessively inherited pure cerebellar ataxia. PMID: 17159980
- This study identified a cluster of French-Canadian families with a new recessive ataxia of relatively pure cerebellar type caused by mutations in SYNE1. PMID: 17503513
- Loss of Drop1 expression at early stages in carcinomas of the uterus, cervix, kidney, lung, thyroid and pancreas. PMID: 18709643
- splice site mutation of SYNE-1 gene found in the family is responsible for arthrogryposis multiplex congenita. PMID: 19542096
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Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 8 (SCAR8); Emery-Dreifuss muscular dystrophy 4, autosomal dominant (EDMD4)
Subcellular Location
Nucleus outer membrane; Single-pass type IV membrane protein; Cytoplasmic side. Nucleus. Nucleus envelope. Cytoplasm, cytoskeleton. Cytoplasm, myofibril, sarcomere. Note=The largest part of the protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane. In skeletal and smooth muscles, a significant amount is found in the sarcomeres. In myoblasts, relocalized from the nuclear envelope to the nucleus and cytoplasm during cell differentiation.; [Isoform GSRP-56]: Golgi apparatus.
Protein Families
Nesprin family
Tissue Specificity
Expressed in HeLa, A431, A172 and HaCaT cells (at protein level). Widely expressed. Highly expressed in skeletal and smooth muscles, heart, spleen, peripheral blood leukocytes, pancreas, cerebellum, stomach, kidney and placenta. Isoform GSRP-56 is predomi
