nesprin-2; nuclear envelope spectrin repeat protein 2; nucleus & actin connecting element protein; protein NUANCE; synaptic nuclear envelope protein 2; syne-2 (SYNE2, KIAA1011, NUA)

Function

• multi-isomeric modular protein which forms a linking network between organelles & the actin cytoskeleton to maintain the subcellular spatial organization
• component of SUN-protein-containing multivariate complexes
• involved in the maintenance of nuclear organization & structural integrity
• connects nuclei to the cytoskeleton by interacting with the nuclear envelope & with F-actin in the cytoplasm
• required for centrosome migration to the apical cell surface during early ciliogenesis
• interacts with F-actin via its N-terminal domain
• interacts with EMD, LMNA & MKS3

Structure

• the KASH domain mediates the nuclear envelope targeting
• belongs to the nesprin family
• contains 1 actin-binding domain
• contains 2 CH (calponin-homology) domains
• contains 1 KASH domain
• contains 13 LRR repeats (leucine-rich repeats)
• contains 9 spectrin repeats

Compartment

• nuclear outer membrane
• single-pass type 4 membrane protein; cytoplasmic side (putative)
• sarcoplasmic reticulum membrane
• plasma membrane
• cytoplasm, cytoskeleton
• mitochondrion
• nucleus, nucleoplasm
• different isoform patterns are found in different compartments of the cell
• isoforms having the C-terminal transmembrane span can be found in several organellar membranes like the
  • nuclear envelope
  • sarcoplasmic reticulum of myoblasts
  • lamellipodia & focal adhesions at the plasma membrane
• the largest part of the outer nuclear membrane-associated protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane
• remains associated with the nuclear envelope during its breakdown in mitotic cells
• shorter solubles isoforms can be found in the cytoplasm & within the nucleus

Alternative splicing

• named isoforms=9
• isoforms produced by exon skipping that results in a frameshift

Expression

• widely expressed
• high expression in kidney, adult & fetal liver, stomach & placenta
• weak expression in skeletal muscle & brain

isoform 5 is highly expressed in pancreas, skeletal muscle & heart

Pathology

• defects in SYNE2 are the cause of Emery-Dreifuss muscular dystrophy type 5

More general terms

• nesprin
• leucine-rich repeat-containing protein (LRRC)

Component of

• SUN-protein-containing multivariate complex (LINC complex)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=23224
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23224
• OMIM: https://mirror.omim.org/entry/608442
• OMIM: https://mirror.omim.org/entry/612999
• UniProt: http://www.uniprot.org/uniprot/Q8WXH0.html