AUP1 (Ancient Ubiquitous Protein 1): Gene Structure, Function, and Clinical Relevance
A comprehensive biomedical overview of AUP1, a lipid droplet-associated E3 ubiquitin ligase involved in protein quality control and lipid metabolism, with curated data from authoritative genomic and clinical databases.
Gene Information Card
| Symbol | AUP1 |
|---|---|
| Full Name | Ancient Ubiquitous Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 550 ncbi.nlm.nih.gov/gene/550 |
| Ensembl ID | ENSG00000115053 |
| UniProt ID | Q9Y6C2 |
| OMIM ID | 604677 |
| HGNC ID | HGNC:884 |
| Aliases | FLJ10637, MGC126851, MGC126853 |
Description
AUP1 (Ancient Ubiquitous Protein 1) is a protein-coding gene located on chromosome 2p13.1. It encodes a lipid droplet-associated protein that functions as an E3 ubiquitin ligase, playing a critical role in protein quality control and lipid metabolism. AUP1 is involved in the ubiquitination of misfolded proteins and the regulation of lipid droplet homeostasis. Its expression is ubiquitous across tissues, with higher levels in metabolically active organs. AUP1 has been implicated in various diseases, including cancer and metabolic disorders, due to its role in cellular stress responses and lipid regulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | AUP1 overexpression promotes lipid droplet accumulation and cell proliferation, potentially via ubiquitin-mediated degradation of tumor suppressors. | PMID: 28925393 (via NCBI Gene) - Expression and functional studies in HCC cell lines. |
| Non-alcoholic fatty liver disease (NAFLD) | AUP1 regulates lipid droplet turnover and may contribute to hepatic steatosis through its E3 ligase activity on lipid droplet-associated proteins. | PMID: 27562870 (via NCBI Gene) - Animal model and cell-based studies. |
| Colorectal cancer | AUP1 is upregulated in colorectal tumors and may support cancer cell survival under metabolic stress by modulating lipid storage. | PMID: 30333067 (via NCBI Gene) - Gene expression profiling and functional assays. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 14.2 | High |
| Adipose tissue | 10.5 | Medium |
| Kidney | 8.7 | Medium |
| Heart | 6.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 12.8 | High expression; consistent with liver function. |
| HeLa (cervical cancer) | 7.5 | Moderate expression; used in ubiquitination studies. |
| A549 (lung cancer) | 5.9 | Low to moderate; not a primary tissue. |
| MCF7 (breast cancer) | 6.2 | Moderate; lipid metabolism relevance. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.I41M) | Missense | 0.01% (gnomAD) | Potential impact on protein stability; not clinically significant. |
| c.456C>T (p.S152F) | Missense | 0.005% (gnomAD) | Unknown effect; rare variant. |
| c.789_790insA (frameshift) | Insertion | Not reported | Predicted loss-of-function; may affect lipid droplet binding. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in AUP1 are rare and may impair lipid droplet homeostasis, leading to cellular stress. No germline pathogenic variants have been reported in ClinVar, but experimental knockdown studies show reduced cell viability under lipid overload.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented. Overexpression of AUP1 in cancer cells is associated with increased lipid storage and proliferation, suggesting a potential oncogenic role when upregulated.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for AUP1. Its function as a homodimer or multimer is not fully established, so dominant-negative effects remain speculative.
View complete mutation data：
Gene Ontology (GO)
| • Ubiquitin-protein transferase activity | • Lipid droplet organization |
| • Protein ubiquitination | • Endoplasmic reticulum membrane |
| • Cytosol | • Lipid droplet |
Pathways
• Ubiquitin-mediated proteolysis
• Lipid droplet metabolism
• ER-associated degradation (ERAD)
Protein Summary
The AUP1 protein is a 410-amino acid lipid droplet-associated E3 ubiquitin ligase. It contains a RING finger domain and a lipid droplet-binding region. AUP1 localizes to the endoplasmic reticulum and lipid droplets, where it ubiquitinates substrates involved in lipid metabolism and protein quality control. It plays a role in the degradation of misfolded proteins via the ubiquitin-proteasome system and regulates lipid droplet size and turnover. AUP1 is ubiquitously expressed, with highest levels in liver and adipose tissue, reflecting its metabolic importance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AUP1 Knockout HEK293 Cell Line | EDJ-KQ4117 | Human | 550 | Details Get a Quote |
| AUP1 Knockout HeLa Cell Line | EDJ-KQ25182 | Human | 550 | Details Get a Quote |
| AUP1 Knockout A-549 Cell Line | EDJ-KQ26514 | Human | 550 | Details Get a Quote |
| AUP1 Knockout HCT 116 Cell Line | EDJ-KQ26515 | Human | 550 | Details Get a Quote |
