Affinage

SUN1

SUN domain-containing protein 1 · UniProt O94901

Length
785 aa
Mass
87.1 kDa
Annotated
2026-06-10
68 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SUN1 is an integral inner nuclear membrane protein that forms the nucleoplasmic half of the LINC complex, mechanically coupling chromatin and the nuclear lamina to the cytoskeleton: its N-terminal nucleoplasmic domain binds lamin A and its C-terminal luminal SUN domain engages the KASH domains of nesprins, building a continuous bridge across the nuclear envelope (PMID:16648470, PMID:16079285). SUN1 is required for nuclear-envelope retention of nesprins via the conserved PPPX motif, and it forms highly immobile oligomers through a self-associating C-terminal coiled-coil that also heterodimerizes with SUN2 (PMID:16079285, PMID:18845190); its luminal region adopts a flexible trimeric coiled-coil architecture that may extend the LINC network through domain-swap interactions (PMID:37416798). Through nesprin connections to dynein/dynactin and kinesin, SUN1 (acting redundantly with SUN2) anchors and moves nuclei during interkinetic nuclear migration, photoreceptor positioning, and myonuclear anchorage (PMID:19509342, PMID:21177258). SUN1 couples microtubules to the lamina and tunes cytoskeletal signaling, regulating focal-adhesion maturation and integrin/traction force, endothelial junction stability via a microtubule–GEF-H1–Rho axis, and front-rear cell polarity through a SUN-domain-determined function distinct from SUN2 (PMID:35663386, PMID:36989130, PMID:41366027). In meiosis, SUN1 specifically attaches telomeres to the nuclear envelope, interacting with the KASH protein KASH5/CCDC155, MAJIN, and a SPDYA-CDK2 module to assemble a telomere supramolecular ring that drives homolog pairing and synapsis; loss of Sun1 abolishes gametogenesis (PMID:17543860, PMID:22826121, PMID:34039995, PMID:33015044, PMID:35587281). Beyond mechanical coupling, SUN1 associates with nuclear pore complexes to promote their interphase assembly and distribution, and it directly binds NXF1 and Nup153 to support NXF1-dependent mRNA export, a function regulated by PKC phosphorylation of S113 (PMID:17724119, PMID:21727197, PMID:26476453, PMID:28831067). Mitotic phosphorylation by Cdk1 (S48, S333) and Plk1 (S138) loosens SUN1's nucleoplasmic interactions while preserving the core SUN-KASH bridge (PMID:25482198). Pathologically, SUN1 over-accumulation driven by its dysregulated interaction with farnesylated progerin is a common event in laminopathies, and reducing SUN1 rescues nuclear defects in HGPS and EDMD models (PMID:22541428, PMID:24522183).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 2006 High

    Established the founding LINC architecture by showing SUN1 physically bridges the lamina to the cytoskeleton, answering how the inner nuclear membrane connects to cytoplasmic structures.

    Evidence Yeast two-hybrid, Co-IP, and domain mapping defining lamin A binding by the N-terminus and nesprin KASH binding by the SUN domain, confirmed by an independent lab the same year

    PMID:16079285 PMID:16648470

    Open questions at the time
    • Stoichiometry and structure of the SUN-KASH interface not resolved
    • Whether B-type lamins also engage SUN1 not addressed here
  2. 2006 Medium

    Mapped the determinants of SUN1 NE targeting, showing the N-terminal ~300 residues are required and the SUN domain dispensable, and that anchoring is lamin-independent.

    Evidence Truncation mutants, RNAi lamin knockdown, immunofluorescence and FRAP

    PMID:16445915

    Open questions at the time
    • The molecular retention partner within the N-terminus not identified
    • Apparent tension with later lamin-dependent recruitment models not reconciled
  3. 2007 High

    Extended SUN1's role beyond the LINC bridge to nuclear pore complex organization, showing it associates with NPCs and maintains their even distribution.

    Evidence Immunofluorescence, immunoelectron microscopy, RNAi, and topology analysis showing NPC clustering on SUN1 loss

    PMID:17724119

    Open questions at the time
    • Direct NPC-binding partner not identified at this stage
    • Mechanism distinguishing SUN1 from SUN2 in NPC association unknown
  4. 2007 High

    Defined a meiotic function by showing SUN1 tethers telomeres to the NE for homolog pairing, explaining a non-somatic role of the LINC complex.

    Evidence Sun1 knockout mice with FISH and immunofluorescence showing failed telomere attachment, pairing, and sterility

    PMID:17543860

    Open questions at the time
    • The telomere-side and force-generating partners not yet identified
    • How telomere movement couples to the cytoskeleton unresolved
  5. 2008 High

    Explained SUN1's immobility and network potential by demonstrating disulfide-linked self-oligomerization and heterophilic association with SUN2.

    Evidence Inverse FRAP, cross-linking, and mutagenesis defining coiled-coil dimers/tetramers

    PMID:18845190

    Open questions at the time
    • Physiological oligomeric state in intact LINC complexes not defined
    • Functional consequence of SUN1-SUN2 heteromers unclear
  6. 2009 High

    Demonstrated genetic redundancy of SUN1 and SUN2 in nuclear anchoring and connected the complex to nesprin localization in muscle.

    Evidence Single and double Sun1/Sun2 knockout mice with graded phenotypes and Nesprin-1 mislocalization

    PMID:19509342

    Open questions at the time
    • Isoform-specific contributions within muscle not dissected
    • Mechanical force requirements not measured
  7. 2009 Medium

    Identified a transcriptional/gene-regulatory dimension of SUN1 in gametogenesis, showing it is needed for meiotic gene expression and piRNA production.

    Evidence Sun1 knockout transcriptomics and piRNA Northern blot in testes

    PMID:19211677

    Open questions at the time
    • Whether the gene-expression defect is secondary to telomere/pairing failure unresolved
    • No direct SUN1-chromatin mechanism shown
  8. 2011 Medium

    Placed SUN1 in NPC biogenesis by showing it is specifically required for interphase, not post-mitotic, pore assembly.

    Evidence RNAi with cell-cycle staging and co-localization with POM121 at assembly sites

    PMID:21727197

    Open questions at the time
    • Direct molecular role at the assembly intermediate not defined
    • Relationship to NPC clustering phenotype not integrated
  9. 2010 High

    Connected SUN1/SUN2-nesprin-2 complexes to motor-driven nuclear migration in vivo, explaining tissue-level consequences of LINC disruption.

    Evidence Sun1/Sun2 double knockout mice with retinal phenotypes, ERG, and Co-IP linking nesprin-2 to dynein/dynactin and kinesin

    PMID:21177258

    Open questions at the time
    • Direct vs indirect SUN1-motor coupling not separated
    • Force magnitudes during INM not quantified
  10. 2012 High

    Identified the SPDYA/KASH5-dynein axis as the meiotic telomere force machinery downstream of SUN1.

    Evidence Yeast two-hybrid, Co-IP, and mouse genetics showing KASH5 binds SUN1 and recruits dynein-dynactin

    PMID:22826121

    Open questions at the time
    • Stoichiometry of the telomere-LINC assembly not yet resolved
    • Regulation of attachment timing unknown
  11. 2012 Medium

    Revealed a DNA-damage-response role for SUN proteins, linking them to ATM/H2A.X activation and DNA-PK.

    Evidence Sun1/Sun2 double knockout MEFs with S-phase arrest and Co-IP with DNA-PK components

    PMID:22863315

    Open questions at the time
    • Direct vs indirect SUN-DNA-PK interaction not validated reciprocally
    • Whether the phenotype reflects mechanics or signaling unresolved
  12. 2012 High

    Established SUN1 over-accumulation as a common pathogenic driver in laminopathies and a therapeutic target, by showing SUN1 removal rescues disease.

    Evidence Sun1 loss in Lmna-/- and progeroid mice extending lifespan, plus SUN1 reduction correcting HGPS fibroblast defects

    PMID:22541428

    Open questions at the time
    • Molecular basis of SUN1 accumulation not defined in this study
    • Tissue-specific contributions to rescue not separated
  13. 2014 High

    Defined the mechanism of pathological SUN1 accumulation as a farnesylation-enhanced progerin-SUN1 interaction occurring during NE reformation.

    Evidence EM, FRAP, Co-IP, and farnesylation mutants showing progerin retains SUN1 in the ER

    PMID:24522183

    Open questions at the time
    • Why accumulation is cumulative across divisions not fully mechanistic
    • Whether this drives all laminopathy pathologies unresolved
  14. 2014 High

    Showed mitotic kinases dynamically remodel SUN1 interactions, explaining how the LINC complex is regulated through the cell cycle.

    Evidence Mass spectrometry phosphosite mapping, kinase assays, and phosphomimetic mutants altering solubility and NE retention

    PMID:25482198

    Open questions at the time
    • Functional consequence for mitotic nuclear envelope breakdown not measured in vivo
    • Phosphatase that reverses these marks unknown
  15. 2014 Medium

    Linked SUN1 point mutations to muscular dystrophy through defective nuclear-microtubule coupling and myonuclear positioning.

    Evidence Patient fibroblasts and C2C12 myotubes expressing A203V/A614V variants with impaired lamin A/C and emerin binding and pericentrin recruitment

    PMID:25210889

    Open questions at the time
    • Causality of variants in patients not established by family genetics here
    • Microtubule nucleation mechanism at the NE not molecularly defined
  16. 2011 Medium

    Connected SUN1 to farnesylated prelamin A recruitment during myoblast differentiation, relevant to EDMD pathology.

    Evidence Immunofluorescence and pharmacological farnesylation inhibition in human myoblasts

    PMID:21311568

    Open questions at the time
    • Direct prelamin A-SUN1 binding not biochemically isolated
    • Causal link to myonuclear positioning correlative
  17. 2015 High

    Assigned SUN1 a direct role in mRNA export, showing it recruits mRNP complexes to the NPC via NXF1 and Nup153.

    Evidence siRNA, Co-IP, GST pulldown, and poly(A)+ RNA in situ hybridization showing nuclear RNA retention on SUN1 loss

    PMID:26476453

    Open questions at the time
    • Whether export and LINC functions are separable not fully resolved
    • Quantitative contribution of SUN1 to bulk export unknown
  18. 2017 Medium

    Identified PKC phosphorylation of S113 as the switch governing the export-competent SUN1-NXF1 interaction.

    Evidence S113A/S113D mutagenesis with poly(A)+ RNA in situ rescue assays

    PMID:28831067

    Open questions at the time
    • Upstream signals activating PKC toward SUN1 unknown
    • In vivo relevance not tested
  19. 2021 High

    Provided structural and in vivo proof that the SUN1-SPDYA-CDK2 module builds the telomere supramolecular ring needed for meiotic pairing.

    Evidence Crystal structure of the ternary complex plus SPDYA-binding-deficient SUN1 knock-in mice

    PMID:34039995

    Open questions at the time
    • How CDK2 activity is timed to attachment not fully defined
    • Ring assembly dynamics not visualized live
  20. 2020 Medium

    Mapped overlapping MAJIN/SPDYA binding sites on the SUN1 N-terminus and showed CDK2-dependent regulation of telomere tethering.

    Evidence Co-IP, GST pulldown, domain mapping, and CDK2 inhibition

    PMID:33015044

    Open questions at the time
    • Competition vs cooperation among partners at overlapping sites unresolved
    • Direct binding affinities not quantified
  21. 2023 High

    Solved the luminal trimeric coiled-coil structure, providing a model for SUN1 flexibility and LINC network formation.

    Evidence X-ray crystallography, SAXS, and molecular dynamics of the luminal region

    PMID:37416798

    Open questions at the time
    • Domain-swap network model not validated in cells
    • Coupling to KASH binding in the full-length protein not shown
  22. 2016 Medium

    Revealed isoform-specific SUN1 functions, with splice variants exerting opposing effects on directional cell migration and B-type lamin binding.

    Evidence Isoform-specific siRNA, overexpression, migration assays, and Co-IP

    PMID:27858498

    Open questions at the time
    • Structural basis of isoform-specific lamin binding unknown
    • Mechanism of opposing migration effects not defined
  23. 2022 Medium

    Showed SUN1 is required for cytoskeletal force generation, integrin activation, and focal adhesion maturation, with SUN2 unable to compensate.

    Evidence siRNA, traction force microscopy, and focal adhesion/integrin assays

    PMID:35663386

    Open questions at the time
    • Molecular link from SUN1 to integrin activation not defined
    • SUN1-specific determinant of this role not mapped
  24. 2022 Medium

    Demonstrated SUN1 organizes NPC concentration along mechanically induced ALL nuclear lines, linking it to mechanoresponsive pore positioning.

    Evidence CRISPR KD/KO under cyclic stretch with nucleoporin quantification

    PMID:36619427

    Open questions at the time
    • Direct nucleoporin partners at ALL lines not all identified
    • Physiological role of ALL-line NPCs unknown
  25. 2023 High

    Placed SUN1 upstream of microtubule-GEF-H1-Rho signaling controlling endothelial junction stability and vascular sprouting.

    Evidence Endothelial knockout mice, zebrafish morpholino, live microtubule imaging, and GEF-H1/nesprin-1 rescue epistasis

    PMID:36989130

    Open questions at the time
    • How SUN1 controls peripheral microtubule stability mechanistically unresolved
    • Direct vs indirect GEF-H1 regulation not separated
  26. 2020 Medium

    Identified a mechanical feedback circuit between the LINC complex and RhoA-actomyosin in vascular smooth muscle.

    Evidence siRNA, FRAP, RhoA activity assays, and pharmacological actomyosin inhibition in VSMCs

    PMID:31935926

    Open questions at the time
    • Directionality of the feedback not fully causal
    • SUN1 vs SUN2 specific contributions intertwined
  27. 2023 High

    Linked SUN1/SUN2 turnover to inflammatory nuclear mechano-remodeling, showing CK2-βTrCP degradation softens the nucleus to enable M1 gene expression.

    Evidence shRNA/siRNA, proteasome inhibitors, ATAC-seq, AFM stiffness, and tumor models showing the transmembrane helix is sufficient

    PMID:37828059

    Open questions at the time
    • How the transmembrane helix alone remodels nuclear mechanics not mechanistic
    • Generality beyond macrophages untested
  28. 2019 Medium

    Uncovered a non-canonical SUN1 role in miRNA biogenesis, with a muscle isoform binding and inhibiting Drosha.

    Evidence Co-IP and miRNA profiling in WT vs SUN1-null myotubes

    PMID:31686651

    Open questions at the time
    • Direct vs indirect Drosha inhibition not fully resolved
    • How a NE protein accesses the microprocessor unclear
  29. 2025 Medium

    Showed elevated SUN1 disrupts cell polarity by coupling stable microtubules to the lamina, with the SUN domain dictating divergence from SUN2.

    Evidence SUN1-SUN2 chimeras, siRNA, microtubule perturbation, and nuclear repositioning assays

    PMID:41366027

    Open questions at the time
    • Why microtubule stabilization inhibits polarity not mechanistic
    • In vivo relevance not tested
  30. 2017 Medium

    Implicated SUN1 in restricting HIV-1 nuclear import in a capsid- and cyclophilin A-dependent manner.

    Evidence Overexpression, CRISPR knockout, chimeric viruses, cyclosporine, and 2-LTR circle quantification

    PMID:29643244

    Open questions at the time
    • Direct SUN1-capsid interaction not demonstrated
    • Why both overexpression and knockdown inhibit import unexplained
  31. 2011 Medium

    Connected SUN1 to DYT1 dystonia by showing it abnormally retains torsinA-ΔE at the NE.

    Evidence siRNA, Co-IP, immunofluorescence, and mutagenesis

    PMID:21627841

    Open questions at the time
    • Whether the SUN1-torsinA interaction is direct unclear
    • Pathogenic significance in patients not established
  32. 2022 Medium

    Demonstrated in human meiosis that the SUN1-CCDC155 complex is required for telomere NE anchoring, extending the mouse model to human fertility disease.

    Evidence Whole-exome sequencing of patients with a CCDC155 mutation and spermatocyte immunofluorescence showing SUN1 mislocalization

    PMID:35587281

    Open questions at the time
    • Single-family genetic evidence
    • Direct mutation effect on binding not biochemically isolated
  33. 2023 Medium

    Linked a common SUN1 variant H118Y to metabolic dysfunction through increased SUN1 degradation, insulin resistance, and lipid accumulation.

    Evidence Proteasome inhibition and cell-based insulin/lipid assays

    PMID:37567366

    Open questions at the time
    • Mechanism connecting SUN1 loss to insulin signaling not defined here
    • In vivo metabolic validation absent
  34. 2025 Medium

    Proposed a metabolic mechanism whereby SUN1-CUL3 binding restrains CUL3 neddylation and IRS ubiquitination, with H118Y impairing this control.

    Evidence AP-MS, Co-IP, neddylation inhibitors, and Western blotting (preprint)

    PMID:42079055

    Open questions at the time
    • Preprint not yet peer-reviewed
    • How a NE protein regulates cytoplasmic CRL activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SUN1's many separable functions — mechanical LINC coupling, NPC assembly, mRNA export, miRNA processing, and metabolic E3-ligase regulation — are partitioned, regulated, and prioritized within a single cell remains unresolved.
  • No unified model separating mechanical from biochemical SUN1 functions
  • Isoform- and tissue-specific function allocation incompletely mapped
  • Structure of the full-length, membrane-embedded SUN1 in an intact LINC complex not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005635 nuclear envelope 3 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1474165 Reproduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-8953854 Metabolism of RNA 2
Partners
CUL3KASH5LMNAMAJINNUP153NXF1SPDYASYNE2
Complex memberships
LINC complextelomere-LINC supramolecular ring (SUN1-KASH5-SPDYA-CDK2)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 SUN1 is an integral inner nuclear membrane protein whose N-terminal nucleoplasmic domain binds lamin A (but not type B lamins) in a detergent-resistant manner, while its C-terminal luminal SUN domain interacts with the KASH domains of nesprins 1 and 2, forming a physical bridge between the nuclear lamina and the cytoskeleton. Yeast two-hybrid screen, co-immunoprecipitation, detergent fractionation, dominant-negative overexpression Molecular and cellular biology High 16079285 16648470
2005 SUN1 is required for nuclear envelope localization of Nesprin-2; the conserved C-terminal PPPX motif of nesprin-1/2 directly interacts with a C-terminal region of SUN1, and knockdown of SUN1 or dominant-negative SUN1 fragments mislocalize Nesprin-2 from the nuclear envelope. Co-immunoprecipitation, dominant-negative overexpression, siRNA knockdown, immunofluorescence Journal of cell science High 16079285
2007 SUN1 (but not SUN2) is intimately associated with nuclear pore complexes (NPCs) as demonstrated by immunofluorescence and immunoelectron microscopy; SUN1 is a type II integral protein of the inner nuclear membrane and NPC association requires synergy of both nucleoplasmic and lumenal domains. Depletion of SUN1 by RNAi or overexpression of dominant-negative SUN1 fragments causes NPC clustering. Immunofluorescence, immunoelectron microscopy, RNAi depletion, topology analysis, dominant-negative overexpression The Journal of cell biology High 17724119
2007 SUN1 at the inner nuclear membrane specifically associates with telomeres during meiotic prophase I (leptotene to diplotene stages); genetic disruption of Sun1 in mice prevents telomere attachment to the nuclear envelope, blocks efficient homolog pairing and synapsis, and causes massive apoptosis abolishing spermatogenesis and oogenesis. Mouse knockout, immunofluorescence, FISH, co-localization studies Developmental cell High 17543860
2008 SUN1 forms highly immobile oligomeric complexes at the nuclear envelope; the C-terminal coiled-coil segment can form dimers and tetramers via self-association, involves interchain disulfide bonds, and supports heterophilic association with SUN2. Both perinuclear and nucleoplasmic SUN1 segments are required for NE immobility. Inverse FRAP, co-immunoprecipitation, biochemical cross-linking, site-directed mutagenesis Biochimica et biophysica acta High 18845190
2009 SUN1 and SUN2 function redundantly in anchoring myonuclei in skeletal muscle; Sun1 single knockout partially disrupts synaptic nuclear anchorage, Sun1/Sun2 double knockout disrupts both synaptic and nonsynaptic nuclear organization, and Syne-1/Nesprin-1 localization at the nuclear envelope is lost in double knockout muscle cells. Mouse knockout (single and double), immunofluorescence, gene dosage analysis Proceedings of the National Academy of Sciences of the United States of America High 19509342
2006 The N-terminal ~300 amino acids of human SUN1 (UNC84A) are crucial for nuclear envelope localization, whereas the conserved C-terminal SUN domain is not required. SUN1 localization and anchoring at the NE is not dependent on lamin proteins, as shown by RNAi knockdown of lamins combined with immunofluorescence and FRAP. RNAi knockdown, truncation mutants, immunofluorescence, FRAP FEBS letters Medium 16445915
2011 SUN1 is required for interphase NPC assembly; it co-localizes with POM121 at forming pore assembly sites, and depletion of Sun1 specifically impairs interphase (but not post-mitotic) NPC assembly. RNAi depletion, live imaging, immunofluorescence, cell-cycle staging The Journal of cell biology Medium 21727197
2012 Accumulation of SUN1 protein is a common pathogenic event in laminopathies: in Lmna−/− and progeroid LmnaΔ9 mice, Sun1 accumulates at the NE; additional loss of Sun1 in these backgrounds markedly reduces tissue pathologies and extends lifespan. In human HGPS fibroblasts, reducing SUN1 overaccumulation corrects nuclear defects and cellular senescence. Double-knockout mice, siRNA knockdown in human cells, histopathology, cell biology assays Cell High 22541428
2012 The germ-cell-specific KASH domain protein KASH5 localizes to telomeres from leptotene to diplotene stages and directly interacts with SUN1 via KASH-related sequences; KASH5 also interacts with the dynein-dynactin complex, connecting the telomere-associated SUN1 to cytoplasmic force-generating machinery for meiotic chromosome movement. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, mouse genetics The Journal of cell biology High 22826121
2012 SUN1 and SUN2 play redundant roles in the DNA damage response; Sun1/Sun2 double-knockout MEFs show premature S-phase arrest, increased apoptosis, DNA damage, decreased perinuclear heterochromatin, and impaired activation of ATM and H2A.X. Biochemical screen identified interactions between SUN1/SUN2 and the DNA-PK complex. Double-knockout MEFs, flow cytometry, immunofluorescence, co-immunoprecipitation, Western blotting Current biology : CB Medium 22863315
2010 SUN1 and SUN2 form complexes with Syne-2/Nesprin-2 at the nuclear envelope and are required for interkinetic nuclear migration (INM) and photoreceptor cell migration in mouse retina; double Sun1/Sun2 knockout causes severe reduction of the outer nuclear layer, photoreceptor mislocalization, and retinal dysfunction. Nesprin-2 complexes with SUN1/2 to connect the nucleus with dynein/dynactin and kinesin motors during nuclear migrations. Mouse double knockout, immunofluorescence, ERG, co-immunoprecipitation Human molecular genetics High 21177258
2011 Farnesylated prelamin A recruits SUN1 to the nuclear envelope during myoblast differentiation; impairment of prelamin A farnesylation alters SUN1 recruitment, and reduced prelamin A and SUN1 levels in EDMD myoblasts correlate with defective myonuclear positioning. Immunofluorescence, pharmacological inhibition of farnesylation, Western blotting, cell fractionation in human myoblasts Cell death and differentiation Medium 21311568
2014 Mitotic phosphorylation of SUN1 at serines 48 and 333 (by Cdk1) and serine 138 (by Plk1) loosens SUN1's interaction with nucleoplasmic binding partners lamin A/C, emerin, and short nesprin-2 isoforms during mitosis, while the C-terminal SUN1-KASH domain interaction with nesprin-2 is maintained. A triple phosphomimetic SUN1 mutant shows increased solubility and reduced NE retention. Mass spectrometry phosphosite identification, site-directed mutagenesis, co-immunoprecipitation, kinase assays, immunofluorescence Nucleus (Austin, Tex.) High 25482198
2014 The dysregulated interaction between SUN1 and progerin (farnesylated mutant lamin A) occurs in the ER during post-mitotic nuclear envelope reformation; farnesylation of progerin enhances its SUN1 interaction, reduces SUN1 mobility, and promotes aberrant ER membrane recruitment of progerin, causing cumulative SUN1 accumulation over successive cell divisions. Two domains of full-length lamin A associate with SUN1, with the farnesylated CaaX motif having stronger affinity. Light and electron microscopy, co-immunoprecipitation, FRAP, domain mapping, farnesylation mutants Journal of cell science High 24522183
2014 SUN1 variants associated with muscular dystrophy (A203V and A614V) show reduced interaction with lamin A/C and emerin; patient fibroblasts and C2C12 myotubes expressing these variants display defective rearward nuclear repositioning, loss of pericentrin recruitment to the NE, and impaired microtubule nucleation at the NE, establishing a direct link between SUN1 mutation and defective nuclear-microtubule coupling and myonuclear positioning. Co-immunoprecipitation, immunofluorescence, nuclear repositioning assays, myotube differentiation PLoS genetics Medium 25210889
2015 SUN1 is required for efficient nuclear mRNA export via the NXF1-dependent pathway; SUN1 depletion causes nuclear accumulation of hnRNP F/H, hnRNP K/J, and poly(A)+ RNA. SUN1 directly interacts with NXF1 to recruit mRNP complexes to the NE, and associates with the NPC through direct interaction with Nup153. siRNA knockdown, co-immunoprecipitation, in situ hybridization for poly(A)+ RNA, leptomycin B treatment, GST pulldown Nucleic acids research High 26476453
2017 The SUN1-NXF1 interaction required for mRNA export is regulated by PKC phosphorylation of serine 113 in the SUN1 N-terminal domain; S113A mutation reduces mRNA export rescue efficiency, while S113D (phosphomimetic) efficiently restores export. Nesprin-2 knockdown also impairs mRNA export, but this effect is independent of SUN1's SUN domain. Site-directed mutagenesis, siRNA knockdown, poly(A)+ RNA in situ hybridization, co-immunoprecipitation Scientific reports Medium 28831067
2021 SUN1 directly interacts with Speedy A (SPDYA), and the crystal structure of the human SUN1-SPDYA-CDK2 ternary complex was determined. SUN1-SPDYA interaction is required for telomere-LINC complex connection and assembly of a ring-shaped telomere supramolecular architecture at the NE, as demonstrated by SPDYA-binding-deficient SUN1 mutant mice that show defective homologous pairing and synapsis. X-ray crystallography, co-immunoprecipitation, mouse knock-in (SUN1 mutant), immunofluorescence, FISH Nature communications High 34039995
2016 SUN1 splice variant SUN1_888, but not the predominant SUN1_916, activates directional cell migration when overexpressed; knockdown of SUN1_888 suppresses cell migration while depletion of SUN1_916 activates it, indicating non-redundant functions. SUN1 (but not SUN2) preferentially interacts with B-type lamins. siRNA knockdown of specific splice variants, overexpression, migration assays, co-immunoprecipitation Nucleus (Austin, Tex.) Medium 27858498
2019 A major muscle-specific isoform of SUN1 binds to and inhibits Drosha (a key microprocessor complex component for miRNA biogenesis); SUN1 null myotubes show altered miRNA profiles including decreased miR-127 (which inhibits RTL1 translation), implicating the LINC complex in muscle regeneration through regulation of miRNA processing. Co-immunoprecipitation, miRNA profiling comparison between WT and SUN1-null myotubes, Western blotting eLife Medium 31686651
2023 SUN1 regulates vascular sprouting and endothelial cell-cell junction stability via microtubules; SUN1 depletion reduces peripheral microtubule density, increases catastrophes, and destabilizes junctions. Mechanistically, SUN1 loss activates Rho via the microtubule-regulated GEF-H1, increasing contractility. Depletion of GEF-H1 or nesprin-1 rescues defective junctions, placing SUN1 upstream of microtubule-GEF-H1-Rho signaling. Endothelial-specific mouse knockout, zebrafish morpholino, live imaging, microtubule dynamics analysis, siRNA rescue experiments eLife High 36989130
2020 SUN1 depletion in VSMCs impairs RhoA activity and actomyosin contractility; inhibition of actomyosin activity (via ROCK inhibition or blebbistatin) reduces SUN2 mobility and decreases SUN2-lamin A association, indicating a mechanical feedback circuit between the LINC complex and RhoA-actomyosin. siRNA knockdown, FRAP, RhoA activity assays, isolated aortic VSMCs from SUN2 KO mice Cells Medium 31935926
2023 The crystal structure of a luminal trimeric coiled-coil domain of SUN1 was solved by X-ray crystallography; combined with light/X-ray scattering and molecular dynamics, a model of SUN1's entire luminal region reveals inherent flexibility between structured domains and suggests domain-swap interactions that may establish a LINC complex network. X-ray crystallography, small-angle X-ray scattering, molecular dynamics simulation Frontiers in cell and developmental biology High 37416798
2024 SUN1 facilitates nuclear influx of CHMP7 (ESCRT-III protein) in sporadic ALS neurons; impaired NPC permeability barrier and SUN1 interactions promote CHMP7 nuclear accumulation, which initiates NPC injury cascades leading to nucleoporin loss and TDP-43 mislocalization. iPSN model of sALS, co-immunoprecipitation, imaging, siRNA knockdown Brain : a journal of neurology Medium 37639327
2023 LPS-induced M1 macrophage polarization decreases SUN1/2 protein levels via a CK2-βTrCP-dependent proteasomal degradation pathway; loss of SUN1/2 shrinks and softens the nucleus, altering chromatin accessibility for M1-associated gene expression. The transmembrane helix of SUN1/2 is required and sufficient for nuclear mechano-remodeling. siRNA/shRNA depletion, proteasome inhibitors, domain deletion mutants, ATAC-seq, AFM nuclear stiffness measurements, mouse tumor models Nature communications High 37828059
2022 SUN1 is required for cytoskeletal force generation and focal adhesion maturation; SUN1 depletion reduces integrin β1 activation, impairs vinculin and zyxin incorporation into nascent focal adhesions, disrupts actin organization, and reduces traction force generation, while SUN2 cannot compensate. siRNA knockdown, traction force microscopy, immunofluorescence, integrin activation assays Frontiers in cell and developmental biology Medium 35663386
2011 SUN1 depletion by siRNA removes DYT1 dystonia torsinA-ΔE (but not ATP-locked torsinA) from the nuclear envelope; torsinA-ΔE localization to the NE requires the torsinA membrane association domain and residue Y147, implicating an abnormal gain-of-function SUN1-torsinA interaction in DYT1 dystonia pathogenesis distinct from the LAP1-torsinA interaction. siRNA knockdown, co-immunoprecipitation, immunofluorescence, site-directed mutagenesis BMC cell biology Medium 21627841
2020 SUN1 interacts with both MAJIN and SPDYA at overlapping N-terminal domain sites; MAJIN interaction is stronger than TERB1 interaction. SPDYA binds SUN1 via its Ringo domain and recruits CDK2; CDK2 inhibition decreases the SUN1-MAJIN interaction, suggesting CDK2-dependent regulation of telomere-NE tethering. Co-immunoprecipitation, GST pulldown, domain mapping, kinase inhibition Frontiers in cell and developmental biology Medium 33015044
2017 Overexpression of SUN1 inhibits HIV-1 infection in a capsid (CA)-dependent manner, blocking nuclear import of viral cDNA; sensitivity to SUN1 depends on the interaction between HIV-1 CA and cyclophilin A (CypA), as cyclosporine treatment or CA-G89A mutation (which abrogates CypA binding) confers resistance. Both SUN1 overexpression and knockdown inhibit HIV-1 nuclear entry. Overexpression, CRISPR knockout, chimeric virus analysis, cyclosporine treatment, 2-LTR circle quantification Journal of virology Medium 29643244
2025 Elevated SUN1 disrupts fibroblast front-rear cell polarity by mechanically coupling microtubules to the nuclear lamina via direct SUN1-lamin A interaction and force transmission through nesprin-2; stable microtubules are necessary and sufficient to inhibit cell polarity; chimeric SUN1-SUN2 proteins show the SUN domain determines their divergent roles in polarization. SUN1-SUN2 chimeric protein expression, siRNA knockdown, microtubule stabilization/depolymerization, nuclear repositioning assays, live imaging Communications biology Medium 41366027
2023 The common SUN1 variant H118Y undergoes increased proteasomal degradation relative to wild-type SUN1; cells expressing H118Y SUN1 exhibit insulin resistance and increased lipid accumulation. Proteasome inhibition, Western blotting, cell-based lipid accumulation and insulin signaling assays Journal of hepatology Medium 37567366
2022 A CCDC155 missense mutation blocks nuclear envelope distribution of SUN1 in human spermatocytes, demonstrating that the SUN1-CCDC155 complex is required for telomere attachment and NE anchoring during human meiosis; loss of this complex causes meiotic arrest in both sexes. Whole-exome sequencing, patient spermatocyte histology, immunofluorescence, co-localization, ex vivo and in vitro expression studies Human genetics Medium 35587281
2022 SUN1 is required for NPC concentration along Actin/LINC/Lamin (ALL) nuclear lines in response to uniaxial cyclic stretch; CRISPR knockdown and knockout of SUN1 significantly diminishes NPC/ALL line integration, with reduced Pom121, TPR, and Nup153 fluorescence at ALL lines. CRISPR SUN1 KD/KO, cyclic stretch, live imaging, immunofluorescence quantification of nucleoporins Heliyon Medium 36619427
2009 Sun1 deficiency in mice leads to repression of meiotic reproductive gene expression in testes and absence of detectable piRNA, identifying an unrecognized role of Sun1 in selective gene expression during gametogenesis. Sun1 knockout mice, transcriptomic analysis, piRNA Northern blot Development (Cambridge, England) Medium 19211677
2025 SUN1 interacts with CUL3 E3 ubiquitin ligase; wild-type SUN1 robustly interacts with CUL3 while H118Y SUN1 shows markedly diminished CUL3 interaction. SUN1 silencing or H118Y expression increases CUL3 neddylation, which promotes CRL-mediated ubiquitination of IRS proteins and insulin resistance; neddylation inhibition restores IRS-1 levels and insulin signaling. Affinity purification-mass spectrometry, co-immunoprecipitation, siRNA knockdown, neddylation inhibitors, Western blotting bioRxiv : the preprint server for biologypreprint Medium 42079055

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. Molecular and cellular biology 420 16648470
2005 The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope. Journal of cell science 346 16079285
2007 SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Developmental cell 343 17543860
2009 SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proceedings of the National Academy of Sciences of the United States of America 199 19509342
2007 Functional association of Sun1 with nuclear pore complexes. The Journal of cell biology 199 17724119
2012 A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis. The Journal of cell biology 195 22826121
2012 Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell 186 22541428
2010 KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development. Human molecular genetics 144 21177258
2014 Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization. PLoS genetics 138 25210889
2015 Global loss of a nuclear lamina component, lamin A/C, and LINC complex components SUN1, SUN2, and nesprin-2 in breast cancer. Cancer medicine 122 26175118
2011 POM121 and Sun1 play a role in early steps of interphase NPC assembly. The Journal of cell biology 112 21727197
2008 Dictyostelium Sun-1 connects the centrosome to chromatin and ensures genome stability. Traffic (Copenhagen, Denmark) 97 18266910
2012 Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Current biology : CB 90 22863315
2008 Sun1 forms immobile macromolecular assemblies at the nuclear envelope. Biochimica et biophysica acta 79 18845190
2011 Prelamin A-mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle. Cell death and differentiation 75 21311568
2009 Requirement for Sun1 in the expression of meiotic reproductive genes and piRNA. Development (Cambridge, England) 64 19211677
2009 SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment, are a functional SUN/KASH pair in Caenorhabditis elegans. Molecular biology of the cell 62 19759181
2006 Nuclear envelope localization of human UNC84A does not require nuclear lamins. FEBS letters 62 16445915
2014 Dysregulated interactions between lamin A and SUN1 induce abnormalities in the nuclear envelope and endoplasmic reticulum in progeric laminopathies. Journal of cell science 59 24522183
2015 Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export. Nucleic acids research 55 26476453
2009 Dictyostelium Sun1 is a dynamic membrane protein of both nuclear membranes and required for centrosomal association with clustered centromeres. European journal of cell biology 41 19632001
2016 SUN1 splice variants, SUN1_888, SUN1_785, and predominant SUN1_916, variably function in directional cell migration. Nucleus (Austin, Tex.) 40 27858498
2014 Mitotic phosphorylation of SUN1 loosens its connection with the nuclear lamina while the LINC complex remains intact. Nucleus (Austin, Tex.) 37 25482198
2013 The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery. The Journal of cell biology 37 24297748
2023 Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation. eLife 36 36989130
2011 The nuclear envelope localization of DYT1 dystonia torsinA-ΔE requires the SUN1 LINC complex component. BMC cell biology 35 21627841
2015 Sun1 deficiency leads to cerebellar ataxia in mice. Disease models & mechanisms 34 26035387
2020 SUN1/2 Are Essential for RhoA/ROCK-Regulated Actomyosin Activity in Isolated Vascular Smooth Muscle Cells. Cells 33 31935926
2023 SUN1/2 controls macrophage polarization via modulating nuclear size and stiffness. Nature communications 31 37828059
2021 The SUN1-SPDYA interaction plays an essential role in meiosis prophase I. Nature communications 31 34039995
2024 SUN1 facilitates CHMP7 nuclear influx and injury cascades in sporadic amyotrophic lateral sclerosis. Brain : a journal of neurology 28 37639327
2016 Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli. Nucleus (Austin, Tex.) 26 26962703
2014 Contribution of SUN1 mutations to the pathomechanism in muscular dystrophies. Human mutation 23 24375709
2022 Homozygous missense mutation in CCDC155 disrupts the transmembrane distribution of CCDC155 and SUN1, resulting in non-obstructive azoospermia and premature ovarian insufficiency in humans. Human genetics 22 35587281
2022 Inner Nuclear Membrane Protein, SUN1, is Required for Cytoskeletal Force Generation and Focal Adhesion Maturation. Frontiers in cell and developmental biology 19 35663386
2017 Effects of Inner Nuclear Membrane Proteins SUN1/UNC-84A and SUN2/UNC-84B on the Early Steps of HIV-1 Infection. Journal of virology 19 28747499
2018 SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A. Journal of virology 18 29643244
2011 Expression of individual mammalian Sun1 isoforms depends on the cell type. Communicative & integrative biology 18 21966565
2019 Telomere elongation through hTERT immortalization leads to chromosome repositioning in control cells and genomic instability in Hutchinson-Gilford progeria syndrome fibroblasts, expressing a novel SUN1 isoform. Genes, chromosomes & cancer 17 30474255
2022 Nuclear pore complexes concentrate on Actin/LINC/Lamin nuclear lines in response to mechanical stress in a SUN1 dependent manner. Heliyon 16 36619427
2020 Tethering of Telomeres to the Nuclear Envelope Is Mediated by SUN1-MAJIN and Possibly Promoted by SPDYA-CDK2 During Meiosis. Frontiers in cell and developmental biology 15 33015044
2019 The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating drosha activity. eLife 14 31686651
2017 The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation. Scientific reports 12 28831067
2012 Reversal of laminopathies: the curious case of SUN1. Nucleus (Austin, Tex.) 11 22895095
2016 Nuclear Envelope Retention of LINC Complexes Is Promoted by SUN-1 Oligomerization in the Caenorhabditis elegans Germ Line. Genetics 8 27098914
2025 A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium berghei. eLife 7 40392232
2023 Loss of SUN1 function in spermatocytes disrupts the attachment of telomeres to the nuclear envelope and contributes to non-obstructive azoospermia in humans. Human genetics 7 36933034
2023 Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1. Frontiers in cell and developmental biology 6 37416798
2023 A common variant that alters SUN1 degradation associates with hepatic steatosis and metabolic traits in multiple cohorts. Journal of hepatology 6 37567366
2025 Depletion of SUN1/2 induces heterochromatin accrual in mesenchymal stem cells during adipogenesis. Communications biology 5 40082539
2020 The SUN1 splicing variants SUN1_888 and SUN1_916 differentially regulate nucleolar structure. Genes to cells : devoted to molecular & cellular mechanisms 5 32931086
2019 Sun1 Mediates Interkinetic Nuclear Migration and Notch Signaling in the Neurogenesis of Zebrafish. Stem cells and development 5 31140357
2017 Data on the association of the nuclear envelope protein Sun1 with nucleoli. Data in brief 5 28580408
2021 Nuclear restriction of HIV-1 infection by SUN1. Scientific reports 4 34580332
2003 Mad1p, a component of the spindle assembly checkpoint in fission yeast, suppresses a novel septation-defective mutant, sun1, in a cell-division cycle. FEMS microbiology letters 4 14592707
2017 SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung adenocarcinoma. OncoTargets and therapy 3 28652764
2012 Dialing down SUN1 for laminopathies. Cell 3 22541423
2025 A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium. bioRxiv : the preprint server for biology 2 39677758
2025 Elevated SUN1 promotes migratory cell polarity defects through mechanically coupling microtubules to the nuclear lamina. Communications biology 2 41366027
2018 Detection of SUN1 Splicing Variants at the mRNA and Protein Levels in Cancer. Methods in molecular biology (Clifton, N.J.) 2 30141053
2025 Endothelial Nucleoporin93 (Nup93) Maintains Vascular Function via Sun1-Dependent Regulation of RhoA-eNOS Signaling. bioRxiv : the preprint server for biology 1 40777343
2023 Allele pairing at Sun1-enriched domains at the nuclear periphery via T1A3 tandem DNA repeats. bioRxiv : the preprint server for biology 1 37066204
2017 SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung adenocarcinoma [Retraction]. OncoTargets and therapy 1 29343968
2026 SV40 exploits the Nesprin-2-SUN1-KPNA4 axis for stepwise targeting and entry into the host nucleus to promote infection. bioRxiv : the preprint server for biology 0 41959248
2026 The inner nuclear membrane protein SUN1 regulates cullin-3 neddylation to maintain insulin signaling. bioRxiv : the preprint server for biology 0 42079055
2026 A Mechano-Feedback Loop Orchestrated by SUN1/2 Governs Cellular Mechanoadaptation via Lamina-Associated Domain Remodeling. Research (Washington, D.C.) 0 42146760
2025 Proteins Lamin A and SUN1 are exclusively decreased in nuclear grade 4 clear cell renal cell carcinoma. Oncology letters 0 41480119
2024 SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression. Journal of cellular and molecular medicine 0 39383106

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