Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SYNE2 contributors: mct - updated : 04-07-2015
HGNC name spectrin repeat containing, nuclear envelope 2
HGNC id 17084
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal CH domain, and an actin-binding site
  • two spectrin repeats
  • a luminal domain binding directly to SUN proteins
  • a region in the rod domain of SYNE2 that is predicted as SMC domain (AA 1436-1766)that can interact with itself, and has the capacity to bind to SMC2 and SMC4, the core subunits of condensin
  • C-terminal single transmembrane domain (KASH domain) spanning the outer nuclear membrane, which mediates nuclear membrane localization, and/or N-terminal paired calponin-homology domains that bind actin
    • mono polymer trimer
    HOMOLOGY
    intraspecies homolog to SYNE1
    Homologene
    FAMILY
  • alpha-actinin type actin-binding proteins family
  • giant spectrin-repeat containing proteins family
    • CATEGORY motor/contractile
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nuclear envelope,ext
    intracellular,nuclear envelope,lumen
    text
  • sarcoplasmic RE, nuclear membrane
  • associate with the NE by virtue of their highly conserved type II transmembrane domain (KASH domain)
  • relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum
  • connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes
    • basic FUNCTION
  • acting as an adapter for assembling multiprotein complexes
  • having a scaffolding function at the nuclear membrane and may be involved in human disease
  • multi-isomeric, spectrin-repeat proteins that bind both emerin and lamins A/C and form a network in muscle linking the nucleoskeleton to the inner nuclear membrane, the outer nuclear membrane, membraneous organelles, the sarcomere and the actin cytoskeleton
  • in combination with two SUN-domain proteins, UNC84A and UNC84B, form a linking complex that couples the nucleoskeleton to the cytoskeleton
  • implicated in nuclear envelope organization and the physical integration of the nucleus with cytoskeletal filaments
  • multifunctional actin-binding and nuclear-envelope-associated protein
  • important scaffold protein implicated in the maintenance of nuclear envelope architecture
  • participate in the LINC complex that links the cytoplasm to the nucleus
  • having potential novel SYNE2 functions in cellular signaling, and positive regulator of the Wnt signaling pathway
  • giant nesprins form a link between the nuclear envelope and the cytoskeleton
  • SYNE2 and SUN1 are involved in an early retinal developmental stage and the loss of function of these proteins eventually leads to an increase in cell death linked to apoptosis
  • SYNE1, SYNE2 act as highly versatile tissue specific intracellular protein scaffolds
  • SYNE2 may have an impact on chromosomes which might be due to its interaction with condensins or to indirect mechanisms provided by its interactions at the nuclear envelope
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of the LINC complex with the nesprin and SUN proteins
  • SYNE2 forms complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus with dynein/dynactin and kinesin molecular motors during the nuclear migrations in the retina
  • SUN2 must form a trimer to bind to SYNE1, SYNE2, and this trimerization is mediated through two predicted coiled-coil regions of the protein, CC1 and CC2, which precede the SUN domain
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds directly to emerin and the C-terminal common region of lamin A/C (LMNA is necessary for the nuclear envelope localization of Nesprin-2)
  • interacting with TOR1A through the KASH domain (role for torsinA in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the nuclear envelope, with torsinA influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement)
  • interacting with UNC84A, and UNC84B
  • interacting with EMD (Nesprin-2 and emerin localize to the nuclear enveloppe)
  • SYNE2 interacts with FSCN1 through a direct, F-actin-independent interaction, and this binding is distinct and separable from a role for fascin within filopodia at the cell periphery
    • cell & other
  • interacting with both dynein/dynactin and kinesin complexes for interkinetic nuclear migration and nuclear migration of photoreceptors during retinal development
    • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EMD5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in Emery-Dreyfuss muscular dystrophy (caused, in part, by uncoupling of the nucleoskeleton and cytoskeleton because of perturbed nesprin/emerin/lamin interactions)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking the actin-binding domain of Nesprin-2 (Nesprin-2DeltaABD), have significant thickening of the epidermis, which is a consequence of the increased epithelial nuclear size
  • Syne-2-/- and Sun1-/- mice exhibit excessive apoptosis in the retina