Ask about this productRelated genes to: SLC33A1 antibody
- Gene:
- SLC33A1 NIH gene
- Name:
- solute carrier family 33 member 1
- Previous symbol:
- ACATN, SPG42
- Synonyms:
- AT-1, AT1
- Chromosome:
- 3q25.31
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-12
- Date modifiied:
- 2016-02-17
Related products to: SLC33A1 antibody
Related articles to: SLC33A1 antibody
- - Source: PubMed
Publication date: 2026/05/01
- The endoplasmic reticulum (ER) requires an oxidative environment to support the efficient maturation of secretory and membrane proteins. This is in part established by glutathione, a redox-active metabolite present in reduced (GSH) and oxidized (GSSG) forms. The ER maintains a higher GSSG:GSH ratio than the cytosol; however, the mechanisms controlling ER redox balance remain poorly understood. To address this, we developed a method for the rapid immunopurification of the ER, enabling comprehensive profiling of its proteome and metabolome. Combining this approach with CRISPR screening, we identified SLC33A1 as the major ER GSSG exporter in mammalian cells. Loss of SLC33A1 led to GSSG accumulation in the ER and a liposome-based assay demonstrated that SLC33A1 directly transports GSSG. Cryogenic electron microscopy structures and molecular dynamics simulations revealed how SLC33A1 binds GSSG and identified residues critical for its transport. Finally, an imbalance in GSSG:GSH ratio induced ER stress and dependency on the ER-associated degradation pathway, driven by a shift in protein disulfide isomerases towards their oxidized forms. Together, our work establishes SLC33A1-mediated GSSG export as a key mechanism for ER redox homeostasis and protein maturation. - Source: PubMed
Publication date: 2026/04/17
Liu ShanshanGad MarkLi CaifanCho KevinLiu YuyangWangdu KhandoBelay ViktorMillet AlonKojima HiroyukiSanford HenryWölk MicheleUrnavicius LinasFedorova MariaPatti Gary JVinogradova Ekaterina VHite Richard KBirsoy Kıvanç - The transcription factor ATF6α has a central role in adapting mammalian cells to ER stress via the unfolded protein response (UPR), prompting efforts to identify ATF6α modulators. Here, an unbiased genome-wide CRISPR-Cas9 screen performed in Chinese Hamster Ovary cells revealed that proteolytic processing of the ATF6α precursor to its active form was impaired in cells lacking the ER-resident solute carrier SLC33A1, a transporter previously implicated in acetyl-CoA import, sialylation, and Nε-lysine protein acetylation. Cells lacking SLC33A1 constitutively trafficked the ATF6α to the Golgi but exhibited impaired Golgi processing and activating proteolysis. IRE1α signalling was derepressed by SLC33A1 deficiency consistent with selective loss of ATF6α-mediated negative feedback in the UPR. -deleted cells accumulated unmodified sialylated N-glycans, precursors to acetylated glycans, likely reflecting impaired glycan processing. Deletion of ER-localised acetyltransferases NAT8 and NAT8B, which catalyse protein Nε-lysine acetylation in the secretory pathway, did not replicate the ATF6α processing defects observed in -deficient cells. Together, our findings highlight a role of SLC33A1-mediated metabolite transport in the post-ER ATF6α maturation, linking small-molecule metabolism to branch-specific signalling in the UPR. - Source: PubMed
Publication date: 2026/04/17
George GintoHarding Heather PKay RichardRon DavidOrdoñez Adriana - Sialic acid O-acetylation is implicated in the modulation of sialoglycan recognition and ganglioside biology. The sugar modification is catalyzed by CASD1, a Golgi membrane protein that encompasses a luminal catalytic domain and a multipass transmembrane domain. The mechanism of how acetyl-CoA is provided to the Golgi remains poorly understood. Here, we show that the acetyl-CoA transporter SLC33A1 provides acetyl-CoA to the luminal domain of CASD1 and that patient-derived SLC33A1 variants linked to inherited neurodevelopmental and neurodegenerative disorders impair ganglioside 9-O-acetylation. Under conditions that enable the formation of 7,9-di-O-acetylated sialoglycans, genetic inactivation of SLC33A1 impaired di-O-acetylation, but unexpectedly, still enabled mono-O-acetylation. Structure prediction and site-directed mutagenesis revealed a second active site in CASD1 that shares striking similarities with the catalytic acetyl-CoA binding transmembrane tunnel of the lysosomal acetyltransferase HGSNAT. Together, our data provide strong evidence that CASD1 has dual functionalities and catalyzes 7,9-di-O-acetylation through SLC33A1-dependent luminal acetylation and SLC33A1-independent transmembrane acetylation. - Source: PubMed
Publication date: 2026/04/01
Albers MalenaBosse LydiaSchröter LarissaJunemann Anna-Maria TRossdam CharlotteHartmann MaikeGrove MelanieLitfin ThomasEgger Anna-SophiaKwiatkowski MarcelThedieck KathrinZocher GeorgBuettner Falk F RMalde Alpeshkumar Kvon Itzstein MarkMühlenhoff Martina - The endoplasmic reticulum (ER) transporter solute carrier family 33 member 1 (SLC33A1) has emerged as an attractive therapeutic target in etiologically diverse diseases, ranging from lung cancer to neurodegenerative disorders. Yet, no pharmacologic SLC33A1 modulators have been described. Here, we show that the small molecule IXA4, a highly selective activator of the adaptive IRE1/XBP1s signaling arm of the unfolded protein response (UPR), binds to SLC33A1 and inhibits its activity. Genetic depletion of phenocopies the selective induction of IRE1/XBP1s signaling brought about by IXA4 treatment. Chemoproteomic analyses and cryo-electron microscopy show that IXA4 binds SLC33A1 within the central channel to inhibit transport of its substrate metabolite(s). Binding of IXA4 to SLC33A1 leads to the accumulation of oxidized glutathione within the ER, hyperoxidizing the ER lumen and inducing activation of adaptive IRE1/XBP1s signaling. Consistent with this function, we find that pharmacologic inhibition of SLC33A1 with IXA4 selectively reduces viability of KEAP1-deficient lung adenocarcinoma cells that have elevated levels of glutathione, mimicking the sensitivity of these cells to genetic deletion of SLC33A1. Our work demonstrates a new physiologic role of SLC33A1 in regulation of ER redox homeostasis and designates IXA4 as a pharmacologic inhibitor of SLC33A1 that can be used to evaluate the biological impact and therapeutic utility of SLC33A1 inhibition in homeostasis and in disease. - Source: PubMed
Publication date: 2026/02/18
Kutseikin SergeiRafiq MariaBora PreronaLiu ShanshanHoman Rick AMindrebo Jeffrey THolcomb MatthewPetrassi H MichaelQiu HuangRedkina AnastasiyaSosna JustynaLee Thanh-TrangHu XiaoForli StefanoParker Christopher GLander Gabriel CBirsoy KivancSaez EnriqueWiseman R Luke