6r15

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

[SUN1_HUMAN] As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton (PubMed:18039933, PubMed:18396275). 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 (By similarity). 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 (By similarity). Involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly (By similarity). Required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis (By similarity). Helps to define the distribution of nuclear pore complexes (NPCs) (By similarity). Required for efficient localization of SYNE4 in the nuclear envelope (By similarity). May be involved in nuclear remodeling during sperm head formation in spermatogenenis (By similarity). May play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links (PubMed:24375709).[UniProtKB:Q9D666]^{[1] [2] [3]} [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.^{[4] [5]}

References

1. ↑ Bupp JM, Martin AE, Stensrud ES, Jaspersen SL. Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3. J Cell Biol. 2007 Dec 3;179(5):845-54. Epub 2007 Nov 26. PMID:18039933 doi:http://dx.doi.org/10.1083/jcb.200706040
2. ↑ 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
3. ↑ Li P, Meinke P, Huong le TT, Wehnert M, Noegel AA. Contribution of SUN1 mutations to the pathomechanism in muscular dystrophies. Hum Mutat. 2014 Apr;35(4):452-61. doi: 10.1002/humu.22504. Epub 2014 Jan 13. PMID:24375709 doi:http://dx.doi.org/10.1002/humu.22504
4. ↑ 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
5. ↑ 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