| Aspect | Key details | Key sources (with year, venue) | URL |
|---|---|---|---|
| Identity | Target verified as rat **Uggt1/UGGT1** (UniProt Q9JLA3), the mammalian **UDP-glucose:glycoprotein glucosyltransferase 1**, an ER quality-control glucosyltransferase distinct from drug-metabolizing UGT1A enzymes, UGGT2, or ceramide glucosyltransferase. It is described as a central ER folding sensor/gatekeeper for N-glycosylated proteins (pqac-00000004, pqac-00000005). | Sagert et al., 2023, *eLife*; Adams et al., 2020, *eLife* | https://doi.org/10.7554/elife.85432 ; https://doi.org/10.7554/elife.63997 |
| Reaction | UGGT1 catalyzes **reglucosylation**: transfer of **glucose from UDP-glucose** onto deglucosylated **N-linked glycans**, e.g. conversion of **Man9GlcNAc2 to Glc1Man9GlcNAc2** on non-native glycoproteins; catalytic activity requires **Ca2+** coordinated by a **DxD motif** (pqac-00000004, pqac-00000007). | Sagert et al., 2023, *eLife* | https://doi.org/10.7554/elife.85432 |
| Substrate specificity | UGGT1 preferentially acts on **non-native/partially folded glycoproteins** and prefers proteins with **exposed hydrophobic regions** over folded proteins. Cellular substrates are enriched for **large, multidomain, heavily glycosylated proteins**; UGGT1 is the dominant mammalian glucosyltransferase and shows preference toward **large plasma-membrane proteins** (pqac-00000002, pqac-00000005, pqac-00000006). | Ninagawa et al., 2024, *eLife*; Adams et al., 2020, *eLife* | https://doi.org/10.1101/2023.10.18.562958 ; https://doi.org/10.7554/elife.63997 |
| Localization | UGGT1 is an **ER-resident/ER-localized luminal enzyme** in the early secretory pathway; both mammalian UGGT1 and UGGT2 are described as ER-localized glycoproteins with **Endo H-sensitive N-glycans** (pqac-00000003, pqac-00000004). | Ninagawa et al., 2024, *eLife*; Sagert et al., 2023, *eLife* | https://doi.org/10.1101/2023.10.18.562958 ; https://doi.org/10.7554/elife.85432 |
| Pathway role | UGGT1 functions in the **calnexin/calreticulin (CNX/CRT) cycle**, re-glucosylating misfolded glycoproteins so they can rebind lectin chaperones and avoid premature ER exit. Newer evidence indicates UGGT1 also **delays glycoprotein ER-associated degradation (gpERAD)**, creating a **“tug-of-war”** between refolding and EDEM/mannose-trimming-driven degradation; proper **ATF6α** function depends on UGGT activity (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000004). | Ninagawa et al., 2024, *eLife*; Sagert et al., 2023, *eLife* | https://doi.org/10.1101/2023.10.18.562958 ; https://doi.org/10.7554/elife.85432 |
| Binding partners | Supported partners include **TAPBPR**, which promotes UGGT1-mediated reglucosylation of peptide-free MHC I, and **SEP15/SELENOF**, a redox-active selenoprotein that forms a stable complex with UGGT1. SEP15 binding maps largely to its **N-terminal cysteine-rich domain (CRD)** and a predicted **SEP15-binding region (SBR)** in UGGT1; prior review evidence cites high-affinity binding (**Kd ~20 nM**) (pqac-00000000, pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000012). | Sagert et al., 2023, *eLife*; Williams et al., 2024, *PNAS*; Kozlov & Gehring, 2020, *FEBS J.* | https://doi.org/10.7554/elife.85432 ; https://doi.org/10.1073/pnas.2315009121 ; https://doi.org/10.1111/febs.15330 |
| Recent 2023-2024 developments | **2023:** Reconstituted human-protein system showed **TAPBPR** is an essential mediator for UGGT1 reglucosylation of peptide-free **MHC I** in at least some allomorphs; UGGT1-catalyzed conversion reached about **80% saturation** in the assay, and Ca2+ was required for catalysis but not for binding to the MHC I–TAPBPR complex (pqac-00000000, pqac-00000007). **2024:** UGGT1 was shown to **compete with ERAD** and inhibit early degradation of unstable/misfolded glycoproteins, including **ATF6α** (pqac-00000001, pqac-00000003). **2024:** AlphaFold2 plus mutagenesis/co-IP refined the **UGGT1–SEP15 interface**, identifying an interface of about **1,860 Å2** and validating UGGT1 interface mutants that strongly reduced SEP15 binding (pqac-00000008, pqac-00000011, pqac-00000013). | Sagert et al., 2023, *eLife*; Ninagawa et al., 2024, *eLife*; Williams et al., 2024, *PNAS* | https://doi.org/10.7554/elife.85432 ; https://doi.org/10.1101/2023.10.18.562958 ; https://doi.org/10.1073/pnas.2315009121 |
| Rat-specific findings | Direct rat evidence is limited but present in **rat liver** metabolic-disease models. In Zucker fatty rats, **Uggt1 mRNA**, **UGGT1 protein**, and **UGGT1 enzymatic activity** are all reduced versus lean controls; in Zucker diabetic fatty rats, mRNA/protein rise relative to obese rats but enzymatic activity remains impaired, indicating discordance between abundance and function under severe metabolic stress (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000020). | Kuribara et al., 2020, *FEBS Letters* | https://doi.org/10.1002/1873-3468.13780 |
| Quantitative stats | Quantitative values supported by evidence include: **71** endogenous UGGT substrates identified in human cells, with a conservative **3-fold enrichment cutoff** for high-confidence substrates (pqac-00000005, pqac-00000006); UGGT2 abundance was about **6.9%** of UGGT1 in HCT116 cells and **29.8%** in HeLa cells (pqac-00000003); in the TAPBPR/MHC I system, UGGT1 reaction saturated at about **80%** (pqac-00000000); the UGGT1–SEP15 predicted interface buries about **1,860 Å2**, and SEP15 co-IP with WT UGGT1 was about **27%**, falling to about **3.8%** or **6.5%** with UGGT1 interface mutants; SELENOF knockout altered glucosylation of **26** proteins, **7** by at least **50%** (pqac-00000008, pqac-00000011, pqac-00000013); in rat ZF liver, Uggt1 mRNA and protein were each about **0.6-fold** of lean controls and activity was about **60% lower**; in ZDF versus ZF, mRNA was **1.7-fold** higher and protein about **1.5-fold** higher, yet activity was about **0.5-fold** (pqac-00000016, pqac-00000018). | Adams et al., 2020, *eLife*; Sagert et al., 2023, *eLife*; Williams et al., 2024, *PNAS*; Kuribara et al., 2020, *FEBS Letters* | https://doi.org/10.7554/elife.63997 ; https://doi.org/10.7554/elife.85432 ; https://doi.org/10.1073/pnas.2315009121 ; https://doi.org/10.1002/1873-3468.13780 |
| Applications | Current applications are mainly **mechanistic and translational** rather than clinical: UGGT1 knowledge is being used to understand **antigen presentation quality control** (MHC I/TAPBPR), to map **ER proteostasis** and **client selectivity**, and to interpret how altered UGGT1 activity affects **glycoprotein maturation** and **metabolic disease-associated ER quality control**. These studies also support proteostasis-oriented strategies in biotechnology and disease models, but no direct rat-specific therapeutic implementation was supported in the gathered snippets (pqac-00000000, pqac-00000001, pqac-00000005, pqac-00000016). | Sagert et al., 2023, *eLife*; Ninagawa et al., 2024, *eLife*; Adams et al., 2020, *eLife*; Kuribara et al., 2020, *FEBS Letters* | https://doi.org/10.7554/elife.85432 ; https://doi.org/10.1101/2023.10.18.562958 ; https://doi.org/10.7554/elife.63997 ; https://doi.org/10.1002/1873-3468.13780 |


*Table: This table summarizes the supported functional annotation of rat Uggt1/UGGT1 (UniProt Q9JLA3), including biochemical function, ER quality-control role, binding partners, recent mechanistic advances, and rat-specific metabolic-disease evidence. It is useful as a compact evidence map before writing the full narrative report.*