SYNE2

Nesprin-2 is a protein that in humans is encoded by the SYNE2 gene. The human SYNE2 gene consists of 116 exons and encodes nesprin-2, a member of the nuclear envelope (NE) spectrin-repeat (nesprin) family. Nesprins are modular proteins with a central extended spectrin-repeat (SR) rod domain and a C-terminal Klarsicht/ANC-1/Syne homology (KASH) transmembrane domain, which acts as a NE-targeting motif. Nesprin-2 (Nesp2) binds to cytoplasmic F-actin, tethering the nucleus to the cytoskeleton and maintaining the structural integrity of the nucleus.

SYNE2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4DXS, 4FI9
Identifiers
Aliases	SYNE2, EDMD5, NUA, NUANCE, Nesp2, Nesprin-2, SYNE-2, TROPH, spectrin repeat containing nuclear envelope protein 2, KASH2
External IDs	OMIM: 608442; MGI: 2449316; HomoloGene: 56700; GeneCards: SYNE2; OMA:SYNE2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q23.2 Start 63,761,899 bp End 64,226,433 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12 C3|12 33.11 cM Start 75,864,908 bp End 76,157,700 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone Skeletal muscle tissue of biceps brachii ganglionic eminence Skeletal muscle tissue of rectus abdominis triceps brachii muscle renal medulla thoracic diaphragm sural nerve epithelium of colon left ovary Top expressed in ventricular zone zygote secondary oocyte neural layer of retina Rostral migratory stream right kidney genital tubercle left lung lobe ganglionic eminence lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function actin filament binding protein binding actin binding Cellular component cytoplasm integral component of membrane nuclear membrane nuclear envelope membrane focal adhesion plasma membrane sarcoplasmic reticulum nucleoplasm aggresome cell junction myofibril Z discdkac meiotic nuclear membrane microtubule tethering complex mitochondrion sarcoplasmic reticulum membrane intermediate filament cytoskeleton nuclear lumen extracellular exosome nuclear outer membrane lamellipodium membrane cytoskeleton nucleus filopodium membrane centrosome Biological process fibroblast migration nuclear envelope organization nuclear migration along microfilament positive regulation of cell migration centrosome localization nuclear migration establishment or maintenance of cell polarity protein localization to nucleus nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration regulation of cilium assembly centriole-centriole cohesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23224 319565 Ensembl ENSG00000054654 ENSMUSG00000063450 UniProt Q8WXH0 Q6ZWQ0 RefSeq (mRNA) NM_015180 NM_182910 NM_182912 NM_182913 NM_182914 NM_001005510 RefSeq (protein) NP_055995 NP_878914 NP_878917 NP_878918 NP_001005510 Location (UCSC) Chr 14: 63.76 – 64.23 Mb Chr 12: 75.86 – 76.16 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

The human SYNE2 gene encodes a protein of 6,885 amino acids (isoform 1, Nesp2 giant); alternative mRNA splicing produces transcripts encoding a larger isoform and numerous smaller isoforms, some of which are specific to various tissues; alternative start and termination sites within the mRNA also allow translation of smaller isoforms, many possessing unique N- or C-terminal sequences encoded by retained introns. Two mechanisms create splice variants of nesprin-2 with the KASH domain deleted (deltaKASH). In deltaKASH1 variants, deletion of cassette exons 111-112 results in a frame shift that disrupts the KASH domain but retains the 3' untranslated region (UTR) in exon 116 utilized for isoforms containing the KASH domain. This mechanism, which also occurs in SYNE1 mRNA encoding nesprin-1 (enaptin), generates deltaKASH1 isoforms terminating with a distinct 11-amino acid tail (GIAGHSATPPA replacing YPMLRYTNGPPPT in isoforms with KASH). Utilization of an alternative stop codon in exon 115, which is followed by a distinct 3' UTR, generates deltaKASH2 variants. This mechanism truncates larger isoforms without generating a distinct C-terminal sequence. Expression of deltaKASH1 variants occurs largely in brain and kidney, with smaller amounts in heart; deltaKASH2 variants are detected in heart and spleen.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Zhang Q, Skepper JN, Yang F, et al. (2002). "Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues". J. Cell Sci. 114 (Pt 24): 4485–98. doi:10.1242/jcs.114.24.4485. PMID 11792814.
• Zhen YY, Libotte T, Munck M, et al. (2003). "NUANCE, a giant protein connecting the nucleus and actin cytoskeleton". J. Cell Sci. 115 (Pt 15): 3207–22. doi:10.1242/jcs.115.15.3207. PMID 12118075.
• Zhang Q, Ragnauth C, Greener MJ, et al. (2003). "The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300". Genomics. 80 (5): 473–81. doi:10.1016/S0888-7543(02)96859-X. PMID 12408964.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Heilig R, Eckenberg R, Petit JL, et al. (2003). "The DNA sequence and analysis of human chromosome 14". Nature. 421 (6923): 601–7. Bibcode:2003Natur.421..601H. doi:10.1038/nature01348. PMID 12508121.
• Schirmer EC, Florens L, Guan T, et al. (2003). "Nuclear membrane proteins with potential disease links found by subtractive proteomics". Science. 301 (5638): 1380–2. Bibcode:2003Sci...301.1380S. doi:10.1126/science.1088176. PMID 12958361. S2CID 23832536.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Zhang Q, Ragnauth CD, Skepper JN, et al. (2005). "Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle". J. Cell Sci. 118 (Pt 4): 673–87. doi:10.1242/jcs.01642. PMID 15671068.
• Cheng J, Kapranov P, Drenkow J, et al. (2005). "Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution". Science. 308 (5725): 1149–54. Bibcode:2005Sci...308.1149C. doi:10.1126/science.1108625. PMID 15790807. S2CID 13047538.
• Libotte T, Zaim H, Abraham S, et al. (2005). "Lamin A/C-dependent localization of Nesprin-2, a giant scaffolder at the nuclear envelope". Mol. Biol. Cell. 16 (7): 3411–24. doi:10.1091/mbc.E04-11-1009. PMC 1165422. PMID 15843432.
• Padmakumar VC, Libotte T, Lu W, et al. (2005). "The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope". J. Cell Sci. 118 (Pt 15): 3419–30. doi:10.1242/jcs.02471. PMID 16079285.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• Wheeler MA, Davies JD, Zhang Q, et al. (2007). "Distinct functional domains in nesprin-1alpha and nesprin-2beta bind directly to emerin and both interactions are disrupted in X-linked Emery–Dreifuss muscular dystrophy". Exp. Cell Res. 313 (13): 2845–57. doi:10.1016/j.yexcr.2007.03.025. PMID 17462627.