| Aspect | Key points | Representative evidence (with citation IDs) |
|---|---|---|
| Identity | Human **AUP1** corresponds to UniProt **Q9Y679**; also called **Ancient ubiquitous protein 1** and described as a **lipid droplet-regulating VLDL assembly factor**. It is a broadly expressed, conserved ~410 aa protein linked to ER protein quality control and lipid droplet biology. | (pqac-00000001, pqac-00000003, pqac-00000004) |
| Domains | Domain architecture includes an **N-terminal hydrophobic hairpin/membrane-inserting region**, a **putative acyltransferase domain** containing the conserved **HX4D** motif, a **CUE ubiquitin-binding domain**, and a **C-terminal G2BR/UBE2G2-binding region**. | (pqac-00000002, pqac-00000003, pqac-00000014, pqac-00000020) |
| Localization | AUP1 localizes to both the **endoplasmic reticulum (ER)** and **lipid droplets (LDs)**. Imaging, flotation, and immuno-EM studies show a major LD pool plus reticular ER staining. | (pqac-00000001, pqac-00000003, pqac-00000018) |
| Membrane topology | AUP1 is inserted in a **monotopic hairpin** topology, with both N- and C-termini facing the cytosol; this topology is important for ER-to-LD targeting. A transmembrane-converted mutant loses LD localization. | (pqac-00000002, pqac-00000014, pqac-00000020) |
| Key interacting partners | Experimentally supported partners include **UBE2G2/UBC7**, **HRD1-SEL1L**, **p97/VCP**, **OS9**, **UBXD8**, **gp78/AMFR**, and **Trc8/RNF139**. AUP1 also interacts with disease-relevant clients such as **apoB100**, **NKCC2**, and **NCC** in specific contexts. | (pqac-00000019, pqac-00000022, pqac-00000024, pqac-00000012) |
| Core mechanism: CUE domain | The **CUE domain** mediates ubiquitin/substrate engagement and promotes interaction with ER quality-control/dislocation machinery. CUE mutations reduce AUP1 association with p97, SEL1L, UBXD8, OS9, UBC6e, and HRD1, and impair substrate-related ubiquitination behavior. | (pqac-00000000, pqac-00000019, pqac-00000021) |
| Core mechanism: G2BR domain | The **G2BR** directly binds **UBE2G2**, recruits it to ER membranes, stabilizes cellular UBE2G2, and allosterically activates ERAD ubiquitination. Structural work showed a conserved interface and **low-nanomolar affinity** for UBE2G2 binding. | (pqac-00000006, pqac-00000016, pqac-00000021) |
| ERAD role | AUP1 is an **ERAD accessory factor** in the **HRD1-SEL1L** complex. It recruits E2 activity, supports ubiquitination of misfolded ER proteins, and is required for efficient degradation of selected ERAD substrates. | (pqac-00000002, pqac-00000005, pqac-00000010, pqac-00000023) |
| Lipid droplet role | AUP1 links ubiquitination machinery to LDs and can influence **LD abundance, clustering, and protein composition**. Monoubiquitinated AUP1 promotes LD clustering, and AUP1 expression affects cellular LD levels. | (pqac-00000001, pqac-00000003, pqac-00000010) |
| Sterol/cholesterol pathway | In lipid droplet-associated ER membranes, AUP1 promotes sterol-induced ubiquitination/ERAD of **HMG-CoA reductase**, **Insig-1**, and **SREBP precursors** by helping recruit E2 activity to **gp78** and **Trc8** complexes. | (pqac-00000007, pqac-00000022) |
| ApoB/VLDL pathway | In hepatocytes, AUP1 interacts with **apoB100**, promotes its ubiquitination/degradation, influences LD size, and thereby regulates **VLDL assembly and secretion**. Knockdown is associated with more **VLDL1-sized apoB100 particles** and increased TG in VLDL-sized fractions. | (pqac-00000004, pqac-00000012, pqac-00000013) |
| 2023–2024 development: viral lipophagy | Recent work reinforced AUP1’s role in **virus-triggered lipophagy**, especially with **UBE2G2** in flaviviral infection. 2023 work showed UBE2G2 is required for replication organelle biogenesis and virus production in conjunction with AUP1. | (pqac-00000008, pqac-00000011) |
| 2023–2024 development: renal ERAD | A 2024 **Cells** study identified AUP1 as a regulator of **NKCC2** and **NCC** ERAD/polyubiquitination in renal cells. AUP1 co-expression lowered NKCC2, while **MG132** or **kifunensine** fully abolished the AUP1 effect. | (pqac-00000009, pqac-00000024) |
| 2023–2024 application: glioma biomarker | A 2023 glioma study found AUP1 is a **poor-prognosis biomarker** associated with **tumor grade**, **TP53 status**, **tumor mutation burden**, proliferation, and inflamed microenvironments. Functional knockdown mainly affected proliferation rather than lipophagy in U87MG cells. | (pqac-00000027) |
| 2023–2024 application: cervical cancer | A 2024 study reported that **KDM5B transcriptionally activates AUP1**, promoting lipid-metabolism reprogramming and malignant progression in cervical cancer; AUP1 knockdown reduced malignant behaviors and lipid metabolic outputs. | (pqac-00000008, pqac-00000025) |
| 2023–2024 application: COVID-19 bioinformatics | AUP1 was identified among **seven lipophagy-related biomarker/drug-target candidates** in COVID-19 transcriptomic analyses, where lipophagy appeared downregulated and lipid-droplet formation upregulated. This is currently computational rather than direct mechanistic validation for AUP1. | (pqac-00000011, pqac-00000026) |
| Quantitative data points | Explicit recent numbers available in accessible sources include: glioma study **TCGA n=690** plus **IHC n=78**; COVID-19 study identified **47** lipophagy-related DEGs (**27 down**, **20 up**) and selected **7** feature proteins; cervical cancer methods used **50 nmol/L** reagents in **3×10^5 cells/well** and viability assays with **2×10^4 cells/well**; cervical cancer burden cited **604,000** new cases and **342,000** deaths in 2020. | (pqac-00000025, pqac-00000026, pqac-00000027) |


*Table: This table summarizes the verified identity, domains, localization, mechanisms, pathways, and recent 2023–2024 applications of human AUP1 (UniProt Q9Y679). It is useful as a compact evidence map linking classic mechanistic studies with newer disease and biomarker contexts.*