| 2006 |
Sec13 and Sec31 form a 2:2 heterotetramer that self-assembles into cuboctahedral cage structures in the absence of Sec23/24, revealing that Sec13/31 has a primary structural role in COPII coat formation. Cryo-EM reconstruction at 30 Å resolution showed a novel cuboctahedron geometry capable of forming a flexible lattice. |
Cryo-electron microscopy and single particle analysis of purified Sec13/31 cages |
Nature |
High |
16407955
|
| 2010 |
The COPII accessory protein Sec16 contains an ACE1 (ancestral coatomer element 1) domain and forms a 2:2 tetramer edge element with Sec13, analogous to the Sec13-Sec31 edge element. Crystal structure at 2.7 Å resolution showed domain swapping at the ACE1-ACE1 interface; in vivo data indicated the ACE1 of Sec31 can functionally replace the ACE1 of Sec16, supporting Sec16 as a scaffold/template for COPII coat assembly. |
X-ray crystallography (2.7 Å crystal structure of Sec16 central domain–Sec13 complex), in vivo complementation assays |
The Journal of cell biology |
High |
20696705
|
| 2009 |
Sec13 participates in the nuclear pore complex (NPC) Y-complex as a structural component forming a heterotrimeric edge element with Nup84 and Nup145C. Crystal structure of the 134-kDa Nup84-Nup145C-Sec13 complex showed that the heterotypic ACE1 interaction of Nup84 and Nup145C is analogous to the homotypic ACE1 interaction of Sec31 in COPII, supporting a common lattice architecture between COPII and NPC scaffolds. |
X-ray crystallography of Nup84-Nup145C-Sec13 complex |
Nature structural & molecular biology |
High |
19855394
|
| 2003 |
Human Sec13 directly interacts with Nup96 at the nuclear pore complex via the WD repeat region of Sec13 and the N-terminal region of Nup96. Sec13 shuttles between intranuclear sites and cytoplasm (shown by FRAP), a fraction is stably associated with NPCs during interphase, and Sec13 contains a nuclear localization signal enabling active nuclear import. |
Yeast two-hybrid, biochemical co-immunoprecipitation, immunofluorescence/confocal/immunoelectron microscopy, photobleaching (FRAP), cotransfection competition assay |
Molecular and cellular biology |
High |
14517296
|
| 2008 |
Sec13 depletion causes concomitant loss of Sec31 and juxtanuclear clustering of Sec23/24-containing pre-budding complexes. Sec13/31 is not required for generation of membrane curvature at the ER (curved coated profiles persist), but efficient coupling of the inner (Sec23/24) and outer (Sec13/31) COPII layers is specifically required for collagen export from the ER in primary fibroblasts, while general secretory cargo (tsO45-G-YFP) export is unaffected. |
siRNA knockdown, electron microscopy, live-cell fluorescence imaging, secretion assays in primary fibroblasts, zebrafish morpholino knockdown |
Journal of cell science |
High |
18713835
|
| 2014 |
The nuclear pore function of Sec13 (distinct from its COPII function) is specifically required for retinal development. Loss of COPII function (sec31a/b knockdown or brefeldin A) did not cause retinal lamination defects, while sec13 mutation caused NPC failure, nuclear mRNA accumulation, and p53-dependent apoptosis in retinal cells. The retinal phenotype was phenocopied by loss of NPC-specific component Nup107. |
Zebrafish genetic model (sec13 sq198 mutant), morpholino knockdown of sec31a/sec31b, brefeldin A treatment, nuclear mRNA localization assay, apoptosis assay, genetic epistasis with nup107 knockdown |
The Journal of biological chemistry |
High |
24627485
|
| 2012 |
In zebrafish, a C-terminal truncation of Sec13 that loses affinity for Sec31a leads to ER structural disintegration in differentiated cells (chondrocytes, intestinal epithelial cells, hepatocytes), triggering unfolded protein response, cell-cycle arrest, and apoptosis, arresting digestive organ growth. This provides direct genetic evidence that COPII function is essential for digestive system organogenesis. |
Zebrafish genetic mutant analysis, co-immunoprecipitation (Sec13 truncation vs. Sec31a), electron microscopy of ER structure, UPR assays, apoptosis assays |
Developmental biology |
High |
22609279
|
| 2010 |
p125A forms a stable ternary complex with Sec13/Sec31A in the cytosol, existing primarily as preassembled Sec13/Sec31A/p125A heterohexamers. p125A binds the C-terminal region of Sec31A (residues 260–600 of p125A) via a domain distinct from its Sec23A-binding domain. Loss of p125A disrupts Golgi morphology and ER protein export. |
Co-immunoprecipitation, gel filtration, immunodepletion, siRNA knockdown with ER export and Golgi morphology assays |
The Journal of cell biology |
High |
20679433
|
| 2011 |
Sec13 is a component of the SEA (Seh1-Associated) complex in yeast, which also contains Seh1, Npr2, Npr3, and Sea1–Sea4 proteins. SEA complex proteins share structural characteristics with COPI, COPII, NPC, and vesicle tethering complexes HOPS/CORVET. The SEA complex dynamically associates with the vacuole in vivo and has roles in intracellular trafficking, amino acid biogenesis, and nitrogen starvation response. |
Mass spectrometry proteomics, co-immunoprecipitation, computational structural modeling, yeast genetics/genetic assays, in vivo vacuole localization |
Molecular & cellular proteomics : MCP |
High |
21454883
|
| 1998 |
The conserved aspartic acid residues in WD repeat blades of Sec13 (yeast) are important but not individually essential for folding of the WD propeller structure. Mutating conserved Asp to Gly in individual blades of Sec13 affects folding in vitro and in COS-7 cells equally; double mutants fold poorly. The repeats most affecting folding differ between Sec13 and Gβ, indicating different folding pathways for different WD repeat proteins. |
Site-directed mutagenesis of conserved Asp residues, in vitro folding assay, expression in COS-7 cells |
The Journal of biological chemistry |
Medium |
9535892
|
| 2017 |
TRAPPIII complex (via its specific subunit TRAPPC12) binds to the Sec13/Sec31A tetramer (but not to Sec13 or Sec31A alone) and positively modulates the assembly of the COPII outer layer during vesicle formation at ER exit sites. TRAPPC12 localizes to ER exit sites/ERGIC, and its deletion disperses the ERGIC and delays ER-to-Golgi transport. |
Co-immunoprecipitation, TRAPPC12 knockout/knockdown, ER-to-Golgi transport assay, immunofluorescence localization |
Scientific reports |
Medium |
28240221
|
| 2018 |
PAQR3 interacts with the WD domains of Sec13 and Sec31A (via its N-terminal end) and facilitates tethering of COPII vesicles to the Golgi. PAQR3 deletion delays ER-to-Golgi trafficking (assessed by BFA washout and RUSH assay). PAQR3 enhances Golgi localization of Sec13 and Sec31A. |
APEX2 proximity labeling, Co-immunoprecipitation, PAQR3 knockout, BFA washout assay, RUSH assay, domain mapping |
iScience |
Medium |
30466064
|
| 2024 |
SPOP mediates K63-linked ubiquitination of Sec13, a component of the GATOR2 complex. K63-ubiquitination of Sec13 attenuates its interaction with other GATOR2 components, thereby suppressing GATOR2 activity and negatively regulating mTORC1 signaling in response to amino acids. SPOP deficiency promotes cancer cell proliferation/migration in a Sec13-dependent manner. |
Co-immunoprecipitation, ubiquitination assay (K63 linkage), Sec13 knockdown rescue experiment, mTORC1 activity assay, cell proliferation/migration assays |
Cellular signalling |
Medium |
38242269
|
| 2022 |
Sec13-dependent COPII protein trafficking is required for oligodendrocyte (OL) differentiation and myelination. Ablation of Sec13 in OL lineage prevents OPC differentiation and inhibits myelination/remyelination. Loss of Sec13 alters the OL secretome and specifically inhibits secretion of pleiotrophin (PTN), which acts as an autocrine factor promoting OL differentiation and myelin repair. |
Conditional Sec13 knockout in OL lineage, remyelination model, secretome analysis, PTN rescue experiments, COPII enhancer (TUDCA) treatment, ectopic COPII component expression |
The Journal of clinical investigation |
Medium |
35143418
|
| 2000 |
Mammalian Sec13 (mSec13p) directly binds rabphilin-11 in cell-free and intact cell systems. The interaction is enhanced by GTP-Rab11p. Disruption of the rabphilin-11–mSec13p interaction by overexpression of the mSec13p-binding domain of rabphilin-11 impairs vesicle trafficking in the perinuclear/Golgi region. |
Cell-free binding assay, co-immunoprecipitation from intact cells, immunofluorescence colocalization, dominant-negative overexpression of binding domain |
The Journal of biological chemistry |
Medium |
10747849
|
| 2009 |
Sec13 directly interacts with presenilin-1 (PS1); the interaction maps to the N-terminal part of the large hydrophilic PS1 cytoplasmic loop and the first WD40-repeat of Sec13. |
Pulldown/binding assay, domain mapping |
Biochemical and biophysical research communications |
Low |
19682973
|
| 2018 |
Sec13 functions as a positive regulator of VISA (MAVS)-mediated antiviral signaling. Sec13 specifically co-immunoprecipitates with VISA. Overexpression of Sec13 increases VISA aggregation and ubiquitination, enhances IRF3 phosphorylation and dimerization, and promotes IFN-β production. Knockdown of Sec13 attenuates Sendai virus-induced IRF3 activation and IFN-β production. |
Co-immunoprecipitation, overexpression and siRNA knockdown, IRF3 phosphorylation/dimerization assays, IFN-β reporter/ELISA |
Virus genes |
Medium |
29948782
|
| 2024 |
Sec13 forms a protein complex with Pgm1 (phosphoglucomutase 1) and Ubqln1. Sec13 inhibits Ubqln1-mediated K48-linked ubiquitination and degradation of Pgm1, thereby stabilizing Pgm1 and promoting glycolysis (G6P and lactate production) in acute lung injury. |
Co-immunoprecipitation, ubiquitination assay, Sec13/Pgm1/Ubqln1 knockdown/overexpression, metabolite measurement (G6P, lactate) |
Biochimica et biophysica acta. Molecular basis of disease |
Low |
39159700
|
| 2018 |
The C-terminal disordered region of Sec31 (residues 820–1220) regulates the flexibility and rigidity of Sec13/31 cages. Deletion of this region produces Sec13/31ΔC cages with more homogeneous size distribution but greater conformational heterogeneity within cuboctahedra. Cryo-EM and MD flexible fitting identified a new hinge for Sec31 β-propeller domain flexing and increased flexibility of a known hinge. |
Cryo-EM, biophysical characterization of purified complexes, molecular dynamics flexible fitting (MDFF) |
Journal of structural biology |
Medium |
30172710
|
| 2005 |
Human Sec13 localizes to kinetochores at metaphase during mitosis. Overexpression of Sec13 causes cells to evade mitotic arrest in response to spindle damage (nocodazole), leading to G1-like phase and apoptotic cell death, and results in giant nuclei formation, suggesting a role in the metaphase/anaphase transition. |
GFP-tagging and live cell imaging, cell cycle analysis, nocodazole treatment, apoptosis assay |
Experimental & molecular medicine |
Low |
16000881
|
| 2011 |
Calcineurin A (Cna1) physically associates with the COPII component Sec13 in Cryptococcus neoformans, as identified by quantitative mass spectrometry and confirmed by co-immunoprecipitation. Cna1 co-localizes with Sec13 at ER-associated puncta during high-temperature stress. |
Mass spectrometry from immunoprecipitation, co-immunoprecipitation, immunofluorescence colocalization |
PloS one |
Low |
21984910
|
| 2023 |
In euglenozoan protists (diplonemids), two Sec13 paralogues have functionally diverged: Sec13a interacts with COPII components and the NPC, while Sec13b interacts with Sec16 and SEA/GATOR complex components. This demonstrates that the three established Sec13 roles (COPII, NPC, SEA/GATOR) can be distributed across paralogues. |
Co-immunoprecipitation/protein interaction studies, subcellular localization imaging, yeast two-hybrid |
Open biology |
Low |
37311539
|
| 2017 |
In C. elegans, the Sec13 orthologue NPP-20 (a nucleoporin) is required for nuclear import of the centromeric protein HCP-4. Knockdown of NPP-20 causes HCP-4 to remain in the cytosol during prophase, preventing its incorporation into centromeres and causing chromosomal segregation defects. |
RNAi knockdown in C. elegans, immunofluorescence localization of HCP-4, chromosome segregation phenotype analysis |
Journal of cell science |
Low |
28122936
|