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Available structures
PDB Ortholog search: PDBe RCSB
Aliases SYNE2, EDMD5, NUA, NUANCE, Nesp2, Nesprin-2, SYNE-2, TROPH, spectrin repeat containing nuclear envelope protein 2
External IDs MGI: 2449316 HomoloGene: 56700 GeneCards: SYNE2
RNA expression pattern
PBB GE SYNE2 202761 s at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 14: 63.85 – 64.23 Mb Chr 12: 75.82 – 76.11 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Nesprin-2 is a protein that in humans is encoded by the SYNE2 gene.[3][4][5] 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.

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.[6]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032. 
  4. ^ Apel ED, Lewis RM, Grady RM, Sanes JR (Nov 2000). "Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction". J Biol Chem. 275 (41): 31986–95. doi:10.1074/jbc.M004775200. PMID 10878022. 
  5. ^ "Entrez Gene: SYNE2 spectrin repeat containing, nuclear envelope 2". 
  6. ^ Rajgor D, Mellad JA, Autore F, Zhang Q, Shanahan CM (Jul 2012). "Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds". PLOS ONE. 7 (7): e40098. doi:10.1371/journal.pone.0040098. PMC 3388047Freely accessible. PMID 22768332. 

Further reading[edit]