SYNE1

This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq]

SYNE1

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.

Biological Process Golgi organizationIDA:UniProtKB1 Publication
Biological Process muscle cell differentiationIDA:UniProtKB1 Publication
Biological Process nuclear matrix anchoring at nuclear membraneIDA:UniProtKB1 Publication
Biological Process nucleus organizationNAS:UniProtKB1 Publication
Biological Process spermatogenesisIEA:UniProtKB-KW

Nucleus outer membrane
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

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.
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.
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.

Cytoplasmic: 1-8746
Helical: 8747-8767
Perinuclear space: 8768-8797

The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.