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.
Gene References into Functions
- variants of EGFR and SYNE2 play an important role in p21 regulation and are associated with the clinical outcome of HBV-related hepatocellular carcinoma in a TP53-indenpdent manner PMID: 27502069
- The authors identified the nuclear envelope protein nesprin-2 as a binding partner for fascin in a range of cell types in vitro and in vivo. Nesprin-2 interacts with fascin through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery. PMID: 27554857
- these data identify N-terminal nesprin-2 variants as novel regulators of beta-catenin signaling. PMID: 27321956
- We show that AMPH-1/BIN1 binds to nesprin and actin, as well as to the microtubule-binding protein CLIP170 in both species. We propose that BIN1 has a direct and evolutionarily conserved role in nuclear positioning, altered in myopathies. PMID: 26506308
- The significance of these shorter isoforms of nesprin, were evaluated. PMID: 24718612
- nesprin-1 and nesprin-2 both regulate nuclear and cytoplasmic architecture. PMID: 24931616
- nesprin-dependent recruitment of kinesin-1 to the nuclear envelope through the interaction of a conserved LEWD motif with kinesin light chain might be a general mechanism for cell-type-specific nuclear positioning during development. PMID: 25516977
- Each mutation in LMNA has a distinct impact on the Nersprin-2 interaction that substantially explains how distinct mutations in widely expressed genes lead to the formation of phenotypically different diseases. PMID: 23977161
- High Nesprin-2 expression is associated with colorectal cancer. PMID: 24080406
- Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds. PMID: 22768332
- Study presents crystal structures of the human SUN2-KASH1/2 complex, i.e. SUN2 complexed with the C-terminal 29 residues of human Nesprin-1 or -2 (the core of the LINC complex). PMID: 22632968
- novel isoform, nesprin-2-epsilon, was found to be the major mRNA and protein product of the nesprin-2 gene. PMID: 21820406
- Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development PMID: 20108321
- Nesprin-2 interacts with {alpha}-catenin and regulates Wnt signaling at the nuclear envelope. PMID: 20801886
- Novel nuclear nesprin-2 variants tether active extracellular signal-regulated MAPK1 and MAPK2 at promyelocytic leukemia protein nuclear bodies and act to regulate smooth muscle cell proliferation. PMID: 19861416
- Nesprin-2 binds lamin and emerin at the nuclear envelope in skeletal muscle. PMID: 15671068
- Nesprin-2 has a scaffolding function at the nuclear membrane PMID: 15843432
- The Nesprin-2 the conserved C-terminal amino acids PPPX is essential for the interaction with a C-terminal region in Sun1. PMID: 16079285
- The characterisation of the residues both in emerin and in nesprin-1alpha and -2beta which are involved in their interaction is reported. PMID: 17462627
- Screening for DNA variations in the genes encoding nesprin-1 (SYNE1) and nesprin-2 (SYNE2) in 190 probands with Emery Dreifuss muscular dystrophy identified four heterozygous missense mutations. PMID: 17761684
- propose nesprin-2 giant as a structural reinforcer at the nuclear envelope in LMNA S143F progeria cells PMID: 17881656
- Nesprin-2 is an important scaffold protein implicated in the maintenance of nuclear envelope architecture. PMID: 18477613
- association with human nesprin-3 appeared to be stronger for torsinADeltaE than for torsinA. TorsinA also associated with the KASH domains of nesprin-1 and -2 PMID: 18827015
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Involvement in disease
Emery-Dreifuss muscular dystrophy 5, autosomal dominant (EDMD5)
Subcellular Location
Nucleus outer membrane; Single-pass type IV membrane protein; Cytoplasmic side. Sarcoplasmic reticulum membrane; Single-pass type IV membrane protein. Cell membrane; Single-pass membrane protein. Cytoplasm, cytoskeleton. Mitochondrion. Nucleus, nucleoplasm. Cytoplasm, myofibril, sarcomere, Z line.
Protein Families
Nesprin family
Tissue Specificity
Widely expressed, with higher level in kidney, adult and fetal liver, stomach and placenta. Weakly expressed in skeletal muscle and brain. Isoform 5 is highly expressed in pancreas, skeletal muscle and heart.
