Ask about this productRelated genes to: SEC23IP antibody
- Gene:
- SEC23IP NIH gene
- Name:
- SEC23 interacting protein
- Previous symbol:
- -
- Synonyms:
- p125
- Chromosome:
- 10q26.11-q26.12
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-03
- Date modifiied:
- 2018-02-13
Related products to: SEC23IP antibody
Related articles to: SEC23IP antibody
- About one-third of the eukaryotic proteome transits the secretory pathway to reach its correct cellular or extracellular destination. At the earliest stage, transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) or Golgi apparatus is mediated by coat protein complex II (COPII). COPII coats consist of inner and outer layers formed by Sec23-Sec24 heterodimers and Sec13-Sec31 heterotetramers, respectively, which initially assemble at ER exit sites (ERES) to form transport carriers. Sec23-interacting protein (Sec23IP) links the inner and outer coats through its interactions with both Sec23A and Sec31A, positioning it as a key potential regulator of COPII function. However, the mechanisms controlling Sec23IP activity remain poorly understood. Here, we investigate how physiological stimuli regulate COPII function through the dynamic modification of Sec23IP by O-linked β-N-acetylglucosamine (O-GlcNAc), a reversible, intracellular form of glycosylation. We first validated Sec23IP as a bona fide O-GlcNAcylated protein. Rescue experiments in Sec23IP knockout cells with a nearly unglycosylatable mutant protein demonstrated the essential role of O-GlcNAcylation in the intrinsically disordered domain in protein transport and in recruiting Sec31A to ERES. Moreover, O-GlcNAcylation of Sec23IP increased during protein transport, coinciding with a reduction in its interaction with Sec31A. These results indicate that distinct site-specific O-GlcNAcylation of Sec23IP spatiotemporally modulates its association with Sec31A to fine-tune ERES recruitment and COPII assembly/disassembly. Our work provides new insight into Sec23IP regulation and suggests that O-GlcNAc on other COPII proteins may govern carrier formation, uncoating, and transport. - Source: PubMed
Publication date: 2026/07/22
Hirata TetsuyaNguyen QuyenLiu CocoBoyce Michael - About one-third of the eukaryotic proteome transits the secretory pathway to reach its correct cellular or extracellular destination. At the earliest stage, transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) or Golgi apparatus is mediated by coat protein complex II (COPII). COPII coats consist of inner and outer layers formed by Sec23-Sec24 heterodimers and Sec13-Sec31 heterotetramers, respectively, which initially assemble at ER exit sites (ERES) to form transport carriers. Sec23-interacting protein (Sec23IP) links the inner and outer coats through its interactions with both Sec23A and Sec31A, positioning it as a key potential regulator of COPII function. However, the mechanisms controlling Sec23IP activity remain poorly understood. Here, we investigate how physiological stimuli regulate COPII function through the dynamic modification of Sec23IP by O-linked β--acetylglucosamine (O-GlcNAc), a reversible, intracellular form of glycosylation. We first validated Sec23IP as a bona fide O-GlcNAcylated protein. Rescue experiments in Sec23IP knockout cells with a nearly unglycosylatable mutant protein demonstrated the essential role of O-GlcNAcylation in the intrinsically disordered domain in protein transport and in recruiting Sec31A to ERES. Moreover, O-GlcNAcylation of Sec23IP increased during protein transport, coinciding with a reduction in its interaction with Sec31A. These results indicate that distinct site-specific O-GlcNAcylation of Sec23IP spatiotemporally modulates its association with Sec31A to fine-tune ERES recruitment and COPII assembly/disassembly. Our work provides new insight into Sec23IP regulation and suggests that O-GlcNAc on other COPII proteins may govern carrier formation, uncoating, and transport. - Source: PubMed
Publication date: 2025/12/20
Hirata TetsuyaNguyen QuyenLiu CocoBoyce Michael - With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H/HeJ ovariectomized (OVX) mice. : The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. : In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism. - Source: PubMed
Publication date: 2025/09/27
Sáez-Chandía JorgeCastillo-Quispe StephannyOkamoto KeiichiroKurahashi AtsushiKodaira KazuyaAihara KotaroSuzuki-Barrera KiyokoKaku MasaruMikami YoshikazuTerunuma MihoYamamura KensukeHayashi TakafumiSaeki MakioKakihara Yoshito - COPII-coat proteins play a crucial role in generating small vesicles at endoplasmic reticulum (ER) exit sites (ERES). However, they also assemble at the necks of tunnels and tubules connecting the ER exit site (donor) to the ERGIC/cis-Golgi cisterna (acceptor). How can COPII support these two traffic mechanisms? Through cell-free reconstitutions, we have found that the apposition of donor and acceptor membranes is important for the assembly of the outer layer of the COPII coat (Sec13/31) but had minimal impact on Sar1-induced COPII inner layer (Sec23/24) recruitment. The expression of the adaptor protein p125A, which binds to phosphatidylinositol 4-phosphate (PI4P), Sec31 and Sec23, stabilized the contact between the donor and acceptor membranes and promoted COPII outer layer assembly. A p125A-chimera expressing a Golgi-targeted PI4P-binding domain could also support outer layer assembly. Notably, the C-terminal helical domain of Sec31A, which interacts with p125A, was essential for its assembly at ERES. In cells lacking p125A, the assembly of the COPII outer layer was selectively destabilized. Transcriptome and secretome analyses reveal selective adjustments to extracellular matrix remodeling and collagen secretion, which corresponded with selective inhibition of fibrillar collagen traffic from the ER. Thus, p125A connects the outer COPII layer at ERES with PI4P-rich ERGIC/cis-Golgi membranes, coordinating COPII assembly with tunnel-driven collagen traffic. - Source: PubMed
Publication date: 2025/05/13
Long Kimberly RSingh GazalVillemeur MarieBrouwers NathalieMalhotra VivekRaote IshierAridor Meir - VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconventional cargo carrier that expedites ER-to-Golgi transport. In addition, depletion of VPS13B or Sec23IP delays ER export of procollagen, suggesting a link between procollagen secretion and joint laxity in patients with Cohen disease. Together, our study reveals a crucial role of VPS13B-Sec23IP interaction at the ERES-Golgi interface in the pathogenesis of Cohen syndrome. - Source: PubMed
Publication date: 2024/10/01
Du YuanjiaoFan XinyuSong ChunyuChang WeipingXiong JuanDeng LinJi Wei-Ke