SYNE2

The protein encoded by this gene is a nuclear outer membrane protein that binds cytoplasmic F-actin. This binding tethers the nucleus to the cytoskeleton and aids in the maintenance of the structural integrity of the nucleus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

Full Name

SYNE2

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. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis.

Biological Process

Biological Process centrosome localizationIMP:UniProtKB1 Publication
Biological Process nuclear migrationIMP:UniProtKB1 Publication
Biological Process nuclear migration along microfilamentISS:UniProtKB
Biological Process nucleokinesis involved in cell motility in cerebral cortex radial glia guided migrationIEA:Ensembl
Biological Process positive regulation of cell migrationISS:UniProtKB
Biological Process regulation of cilium assemblyIEA:Ensembl

Cellular Location

Nucleus outer membrane
Sarcoplasmic reticulum membrane
Cell membrane
Cytoplasm, cytoskeleton
Mitochondrion
Nucleus, nucleoplasm
Cytoplasm, myofibril, sarcomere, Z line
Different isoform patterns are found in the different compartments of the cell. The isoforms having the C-terminal transmembrane span can be found in several organellar membranes like the nuclear envelope, the sarcoplasmic reticulum of myoblasts, or the lamellipodia and focal adhesions at the cell membrane. The largest part of the outer nuclear membrane-associated protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane. Remains associated with the nuclear envelope during its breakdown in mitotic cells. Shorter soluble isoforms can be found in the cytoplasm and within the nucleus.
Isoform 8
Cell junction, focal adhesion
In U2OS cells.

Involvement in disease

Emery-Dreifuss muscular dystrophy 5, autosomal dominant (EDMD5):
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.

Topology

Cytoplasmic: 1-6834
Helical: 6835-6855
Perinuclear space: 6856-6885

PTM

The disulfid bond with SUN2 is required for stability of the SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required for the interaction.