4dxr

Structural highlights

Disease

[SYNE1_HUMAN] Autosomal recessive myogenic arthrogryposis multiplex congenita;Autosomal dominant Emery-Dreifuss muscular dystrophy;Autosomal recessive ataxia, Beauce type. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[SUN2_HUMAN] Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. 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. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.^[1] [SYNE1_HUMAN] Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. May be involved in the maintenance of nuclear organization and structural integrity. Connects nuclei to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. May be required for centrosome migration to the apical cell surface during early ciliogenesis.^{[2] [3]}

References

1. ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:http://dx.doi.org/10.1016/j.yexcr.2008.02.022
2. ↑ Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM. Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues. J Cell Sci. 2001 Dec;114(Pt 24):4485-98. PMID:11792814
3. ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:http://dx.doi.org/10.1016/j.yexcr.2008.02.022
4. ↑ Sosa BA, Rothballer A, Kutay U, Schwartz TU. LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins. Cell. 2012 May 25;149(5):1035-47. PMID:22632968 doi:10.1016/j.cell.2012.03.046