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FLASH GENE
Symbol SYNE2 contributors: mct - updated : 04-07-2012
HGNC name spectrin repeat containing, nuclear envelope 2
HGNC id 17084
Corresponding disease
EMD5 Emery-Dreifuss muscular dystrophy 5
Location 14q23.2      Physical location : 64.319.682 - 64.693.165
Synonym name
  • synaptic nuclei expressed gene 2
  • nesprin 2
  • nucleus and actin connecting element
  • nesprin-2 giant nuance
  • polytrophin
  • protein NUANCE
  • Nuclear envelope spectrin-repeat proteins 2
  • Synonym symbol(s) KIAA1011, FLJ45710, FLJ46790, NUA, NUANCE, Nesprin-2, SYNE-2, DKFZP434H2235, FLJ11014, DKFZp686H1931, TROPH, FLJ43727, DKFZp686E01115
    DNA
    TYPE functioning gene
    STRUCTURE 373.49 kb     116 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    KCNH5 14q23.1 potassium voltage-gated channel, subfamily H (eag-related), member 5 ADPRTP2 14q24 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase) pseudogene 2 ARHJ 14q23.1 ras homolog gene family, member J GPB5 14q23.2 glycoprotein beta 5 PPP2R5E 7p12-p11.2 protein phosphatase 2, regulatory subunit B (B56), epsilon isoform LOC390485 14 similar to ribosomal protein L31 GCATP 14q23.2 glycine C-acetyltransferase pseudogene LOC112840 14q23.2 similar to RIKEN cDNA 2600001A11 gene HSPEP2 14 heat shock 10kDa protein 1 (chaperonin 10) pseudogene 2 SGPP1 14q23.1 sphingosine-1-phosphate phosphatase 1 EIF2S2P 14q23.2 eukaryotic translation initiation factor 2, subunit 2 beta, pseudogene SYNE2 14q23.1-q23.2 spectrin repeat containing, nuclear envelope 2 ESR2 14q24.1 estrogen receptor 2 (ER beta) MTHFD1 14q24 methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase AKAP5 14q21-q24 a kinase (PRKA) anchor protein 5 ZNF46 14q22-q24 zinc finger protein 46 (KUP) ZBTB1 14q22.1-q22.3 zinc finger and BTB domain containing 1 HSPA2 14q22 heat shock 70kDa protein 2 C14orf50 14q23.2 chromosome 14 open reading frame 50 NUP50P 14 nucleoporin 50 pseudogene KIAA0599 14q23.3 KIAA0599 SPTB 14q22-q23.2 spectrin, beta, erythrocytic (includes spherocytosis, clinical type I) C14orf52 14q23.2 chromosome 14 open reading frame 52 GPX2 14q24.1 glutathione peroxidase 2 (gastrointestinal) LOC390487 14 similar to Ras-related protein Rab-15 FNTB 14q23.1 farnesyltransferase, CAAX box, beta MAX 14q23.1 MAX protein LOC390488 14 similar to 60S ribosomal protein L21 RPL36AP2 14 ribosomal protein L36a pseudogene 2 PTBP1P 14 polypyrimidine tract binding protein 1 pseudogene
    RNA
    TRANSCRIPTS type messenger
    text alternative promoter usage and splicing produces shorter forms containing spectrin repeats and the KASH domain (PMID: 19008300)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    115 - 21816 796.4 6884 - 2007 17881656
  • N2G, scaffold protein (nesprin-2 giant/NUANCE) essential for emerin anchorage to the inner nuclear membrane
  • composed of an N-terminal -actinin type actin-binding domain (ABD), followed by a long spectrin-repeat-containing rod and a C-terminal KASH domain
  • larger nesprin forms are thought to reside in the outer nuclear membrane
  • FHOD1 is an interaction partner of N2G
  • 9 - 2586 48.2 429 - 2007 17462627
    11 - 2694 62.2 556 - 2007 17462627
    116 - 21882 798.9 6907 - 2009 19008300
  • Nesprin-2-giant
  • larger nesprin forms are thought to reside in the outer nuclear membrane
  • - - - 120 - . located at the nuclear envelope . strongly expressed in ovary, but absent from human skin fibroblasts . strongly in Ntera-2 cells (testicular embryonal carcinoma cell line) 2011 21820406
  • may have a role in very early development or in some ovary-specific function
  • lacking the actin-binding N-terminus
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately Homo sapiens
    Reproductivefemale systemplacenta  highly Homo sapiens
     female systemovary  highly Homo sapiens
     male systemtestis  highly Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • eye, dominant isoform in fetal brain
  • 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
  • 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
  • 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,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
  • 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
  • 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)
  • 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