TXNDC4
- Known as:
- TXNDC4
- Catalog number:
- Y213971
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- TXNDC4
Related genes to: TXNDC4
- Gene:
- ERP44 NIH gene
- Name:
- endoplasmic reticulum protein 44
- Previous symbol:
- TXNDC4
- Synonyms:
- KIAA0573, PDIA10
- Chromosome:
- 9q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-11
- Date modifiied:
- 2018-11-15
Related products to: TXNDC4
Related articles to: TXNDC4
- The biogenesis of secretory proteins proceeds under sequential quality control checkpoints operating along the exocytic pathway. Unlike other chaperones that reside primarily in the endoplasmic reticulum, ERp44 cycles through the Golgi to control the assembly of polymeric proteins and the localization of a few endoplasmic reticulum resident enzymes (ERAP1, Prx4, Ero1α, and SUMF1). To gain information about its pathophysiological role, we generated ERp44-deficient models. ERp44 KO mice are smaller than control siblings, and show skeletal malformations and delayed bone development, with reduced collagen deposition. Similar skeletal defects were also observed in ERp44 knocked down zebrafish embryos, supporting a conserved role for ERp44 in skeletal development. In cellular models, ERp44 downregulation dramatically affects collagen type 1 deposition, causing intracellular procollagen 1 accumulation. We thus conclude that the levels of ERp44 are crucial for efficient collagen deposition. - Source: PubMed
Publication date: 2026/04/16
Pannese MariaCanciani BarbaraCarnovali MartaDalla Torre MarcoGallucci GianpieroMangiavini LauraMariotti MassimoPanina-Bordignon PaolaVan't Hof RobSitia RobertoAnelli Tiziana - Zinc ions (Zn2+) are essential trace metal ions in the human body. Intracellular Zn2+ levels are tightly regulated by two metal transporter families: ZIPs, which mediate Zn2+ influx into the cytosol, and ZnTs, which export Zn2+ from the cytosol to the extracellular space or sequester it into the cellular organelles. Within cells, Zn2+ plays multiple roles, acting as a catalytic cofactor for numerous enzymes, stabilizing protein structures, and functioning as a second messenger in signal transduction. In addition, Zn2+ is involved in the transient regulation of enzymatic activities. Here, we review recent findings that reveal novel roles of Zn2+ in the structural and functional regulations of the molecular chaperone ERp44 and the cargo receptor ERGIC-53, both of which operate for protein quality control in the early secretory pathway. - Source: PubMed
Publication date: 2026/05/05
Watanabe SatoshiInaba Kenji - Zinc homeostasis is crucial for various biological processes, including gene regulation, signal transduction, and proteostasis. ZIP7 is a membrane transporter that exports zinc ions (Zn) from the lumen of the endoplasmic reticulum (ER) to the cytosol, and its dysfunction causes ER stress, although the underlying mechanism remains unclear. Here, we show that ZIP7 inhibition increases the labile Zn concentration in the ER to micromolar levels, approximately 10 times higher than its steady-state level. Such abnormally high Zn concentrations disrupt the function and trafficking of the Zn-dependent chaperone ERp44 at the ER-Golgi interface. In vitro assays using recombinant proteins demonstrated that Zn inhibits the Ero1α-PDI oxidative system, and that ERp44 enhances this inhibitory effect. Consequently, the ER redox environment becomes more reducing, severely impairing the oxidative folding of key membrane receptors such as Notch1 and EGFR. These findings reveal the essential role of zinc homeostasis in redox-dependent proteostasis within the ER. - Source: PubMed
Publication date: 2026/04/22
Amagai YutaArai ChihiroYamamoto WakanaWatanabe SatoshiKowada ToshiyukiSitia RobertoHoseki JunMizukami ShinMatsumoto MasakiInaba Kenji - KDEL receptors (KDELRs) prevent the secretion of soluble chaperones and enzymes meant to reside in the endoplasmic reticulum. While a single KDELR exists in yeast (ERD2), three variants are present in mammals, displaying high sequence similarity. All three can prevent the secretion of KDEL-bearing clients. However, their diverse tissue distribution and the high phylogenetic conservation of the differences suggest functional specialization. Accordingly, we show here that while KDELR2 plays a major role in client retrieval, KDELR1 and KDELR3 regulate the production of AGR2, a key assistant of mucin folding, in opposite ways. AGR2 transcripts increase dramatically upon silencing KDELR3 but decrease when KDELR1 is downregulated. Silencing ERp44, but no other ER residents, phenocopies KDELR3 knockdown, suggesting that AGR2 regulation depends on ERp44-KDELR3 interactions. Our findings identify a novel regulatory circuit, distinct from the unfolded protein response, that controls the molecular composition of the early secretory pathway based on specific interactions between KDELRs and ER residents. - Source: PubMed
Publication date: 2026/02/18
Palazzo Federica CeciliaDalla Torre MarcoAmagai YutaHan XueTempio TizianaValetti CaterinaManteiga Jose GarciaMatsumoto MasakiFeige MatthiasSallese MicheleInaba KenjiSitia RobertoAnelli Tiziana - Microproteins encoded by short open reading frames (sORFs) of <100 codons have been predicted to constitute a substantial fraction of the eukaryotic proteome. However, the relevance and roles of a majority of microproteins remain undefined, as only a small fraction of these intriguing cellular players have been characterized in-depth so far. Here, we use pooled overexpression screens with a library of 11 338 sORFs to overcome the challenge of elucidating which of the thousands of putative translated sORFs are biologically functional. As a proof-of-concept, we performed a phenotypic screen to identify sORFs protecting cells from treatment with the nucleotide analogue 6-thioguanine. With this approach, we identified two cytoprotective microproteins: altDDIT3 and PIPPI. PIPPI is encoded within the LCR16a core duplicon of the Morpheus/NPIP gene cluster. We show that PIPPI modulates the cellular response to protein folding stress in the endoplasmic reticulum (ER) and interacts with proteins in the same pathway, including protein disulfide isomerase ERp44. PIPPI overexpression protects, while PIPPI knockdown sensitizes cells to ER stress. Besides providing mechanistic insights into a new microprotein, this study highlights the power of using pooled overexpression screens to identify functional microproteins. - Source: PubMed
Lafranchi LorenzoRaja Glancis LuzeenaArenas Alberto MSpinner AnnaShrung Kovi RHornisch MaximilianSchlesinger DörteLuzon Carmen NavarroBrinkenstråhle LinusShao RuiPiazza IlariaLehtiö JanneBranca Rui M MElsӓsser Simon J