SYNE1
Domain
The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.
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 spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.
Involvement in disease
Spinocerebellar ataxia, autosomal recessive, 8
SCAR8
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR8 is an autosomal recessive form.
None
The disease is caused by variants affecting the gene represented in this entry.
Emery-Dreifuss muscular dystrophy 4, autosomal dominant
EDMD4
A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.
None
The disease is caused by variants affecting the gene represented in this entry.
Arthrogryposis multiplex congenita 3, myogenic type
AMC3
A form of arthrogryposis multiplex congenita, a heterogeneous group of disorders characterized by multiple joint contractures resulting, in some cases, from reduced or absent fetal movements. AMC3 is an autosomal recessive form characterized by decreased fetal movements, muscular hypotonia, delayed motor development, loss of ambulation, variable skeletal defects, and persistent contractures of interphalangeal joints.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.
Sequence Similarities
Belongs to the 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 predominantly expressed in heart and skeletal muscle (at protein level).
Cellular localization
- Nucleus outer membrane
- Single-pass type IV membrane protein
- Cytoplasmic side
- Nucleus
- Nucleus envelope
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Myofibril
- Sarcomere
- 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
Alternative names
C6orf98, KIAA0796, KIAA1262, KIAA1756, MYNE1, SYNE1, Nesprin-1, Enaptin, KASH domain-containing protein 1, Myocyte nuclear envelope protein 1, Nuclear envelope spectrin repeat protein 1, Synaptic nuclear envelope protein 1, KASH1, Myne-1, Syne-1