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FLASH GENE
Symbol SUN1 contributors: mct/pgu - updated : 29-04-2020
HGNC name Sad1 and UNC84 domain containing 1
HGNC id 18587
DNA
TYPE functioning gene
STRUCTURE 58.29 kb     20 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
18 - 3840 - 702 - 2006 17132086
6 - 1017 - 257 - 2006 17132086
7 - 1221 - 278 - 2006 17132086
17 - 3703 - 682 - 2006 17132086
20 - 3977 - 785 - 2006 17132086
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Endocrineneuroendocrinepituitary  highly
Hearing/Equilibriumear   highly
Nervousspinal cord    
Reproductivefemale systemovary  highly
 male systemtestis  highly
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
Nervouscentral   
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal 300 amino acids crucial for efficient nuclear enveloppe localization of UNC84A, responsible for detergent-resistant association with the nuclear lamina and lamin A binding
  • an AID domain preceding the SUN domain, which adopts a three-helix bundle conformation that interacts with the SUN domain and keeps it in an autoinhibited state
  • conserved C-terminal SUN domain, 175 AA SUN domain, not required for efficient nuclear enveloppe localization, interacts with the mammalian ANC-1 homologs nesprins 1 and 2 via their conserved KASH domain
  • a UNC84 domain may be playing a role in the nuclear anchoring and/or migration
  • HOMOLOGY
    interspecies homolog to murine Sun1
    homolog to C-Elegans Unc-84
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    intracellular,nuclear envelope,int
    text
  • nuclear and perinuclear (integral membrane protein located at the inner nuclear membrane)
  • SUN1 and LMNA colocalize at the Nuclear Envelope (NE)
  • SUN1 deleted for Its N-Terminal Lamin A-Interacting Domain Locates in the Golgi
  • inner nuclear membrane (INM)2 proteins playing a major role in nuclear-cytoplasmic connection by formation of a bridge across the nuclear envelope (NE), known as the LINC complex
  • basic FUNCTION
  • involved in acetylation of histones for de-compacting DNA at the end of mitosis
  • connects the nucleoplasm with the cytoskeleton
  • SYNE2, and SUN1, SUN2 mediate nuclear migration of the photoreceptor cells through bridging microtubules with molecular motors to the nuclei
  • 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
  • nuclear envelope protein involved in nuclear migration, meiotic telomere tethering, and antiviral responses (
  • major role of SUN1 and SUN2 in the nucleo-cytoskeleton interactions and in regulation of nuclear positioning in differentiating cells
  • SUN1 and SUN2 may play a redundant role in DNA damage response (DDR)
  • SUN1 and SUN2 could affect DDR by localizing certain nuclear factors to the nuclear enveloppe or by mediating communication between nuclear and cytoplasmic events
  • role of SUN1, SUN2 proteins in bipolar spindle assembly and mitotic progression
  • important role for SUN1 and SUN2 in muscle disease pathogenesis which support the hypothesis that defects in the LINC complex contribute to disease pathology through disruption of nuclear-microtubule association, resulting in defective myonuclear positioning
  • mitotic phosphorylation of SUN1 disrupts interactions with nucleoplasmic binding partners, promoting disassembly of the nuclear lamina and, potentially, its chromatin interactions
  • inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and it is an integral component of the mammalian mRNA export pathway
  • SUN1 is involved in the HIV-1 nuclear entry process
  • SUN1 modulates gene expression independently of its incorporation into LINC complexes
  • is required for efficient muscle regeneration
  • SUN1, SUN2, SYNE1 (LINC complex) have emerged as a key regulators of actin cytoskeletal organisation
  • LINC complex exists in a mechanical feedback circuit with RHOA to regulate Vascular smooth muscle cells (VSMCs) actomyosin activity and morphology
  • mislocalization of LINC complex proteins (SUN1, SUN2, LMNA, EMD, SYNE1) is a significant characteristic of cellular senescence phenotypes and may influence complex events at the nuclear membrane, including trafficking and heterochromatin attachment
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homodimers and heterodimers with SUN1
  • 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
  • TSNAX
  • interacting with UNC84B to form a physical interaction between the nuclear envelope and the centrosome
  • lamin A-binding protein
  • interact with lamin A (a subset of lamin A mutations, associated with Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome, disrupt lamin A interaction with UNC84B and SUN1)
  • interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton
  • emerin and short SYNE2 isoforms are novel binding partners of both SUN1, UNC84B
  • POM121 and SUN1 interact transiently to promote early steps of interphase Nuclear pore complexes assembly
  • CCDC155 possesses hitherto unknown KASH-related sequences that directly interacted with SUN1 and mediated telomere localization
  • dysregulated interaction of SUN1 and LMNA in the ER during nuclear envelope reformation determines the progression of PRO1
  • SUN1 functions in mammalian mRNA export through the NXF1-dependent pathway, and this interaction SUN1-NXF1is at least partly regulated by a protein kinase C (PKC)
  • SUN1 regulates muscle regeneration by modulating DROSHA activity
  • SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1
  • cell & other
    REGULATION
    Other SUN1 phosphorylation is part of a surveillance mechanism to coordinate chromosome synapsis and recombination with meiotic progression and chromosome movement
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Syne-2-/- and Sun1-/- mice exhibit excessive apoptosis in the retina
  • premature death of progeric and dystrophic mice is ameliorated by removal of Sun1
  • mice depleted of Sun1 showed a marked reduction in the cerebellar volume, and this phenotype is exacerbated with additional loss of a Sun2 allele