Lipid droplet-regulating VLDL assembly factor AUP1 (AUP1)
The protein contains 410 amino acids for an estimated molecular weight of 45787 Da.
Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome (PubMed:18711132, PubMed:21857022). Plays a role in lipid droplet formation (PubMed:21857022). Induces lipid droplet clustering (PubMed:24039768). Recruits ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation (PubMed:23223569, PubMed:21127063). Also required for the degradation of INSIG1, SREBF1 and SREBF2 (PubMed:23223569). Plays a role in regulating assembly and secretion of very low density lipoprotein particles and stability of apolipoprotein APOB (PubMed:28183703).', '(Microbial infection) Following Dengue virus infection, required for induction of lipophagy which facilitates production of virus progeny particles. (updated: Oct. 7, 2020)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
ER-associated misfolded protein catabolic process
Lipid droplet formation
Lipid droplet organization
Lipophagy
Protein localization to lipid droplet
Response to virus
Retrograde protein transport, ER to cytosol
Ubiquitin-dependent ERAD pathway
Viral process
The reference OMIM entry for this protein is 602434
Ancient ubiquitous protein 1; aup1
CLONING
While searching for genes on mouse chromosome 6 between microsatellite markers D6Mit5 and D6Mit21, Jang et al. (1996) found a nonrepetitive 0.7-kb fragment that hybridized to human, cat, and dog DNAs on a zoo blot. Using this fragment as a probe, they cloned cDNAs from mouse neonatal brain and adult mouse testis cDNA libraries. Jang et al. (1996) sequenced overlapping cDNAs and found an open reading frame of 410 amino acids with putative secretion signal sequence at the N terminus and a domain with homology to the 'ancient conserved region' of the ARCN1 gene (600820). They called the new gene AUP1. Northern blot analysis in mouse revealed a 1.5-kb Aup1 transcript in all adult tissues tested and in fetal samples from embryonic days 10 to 14. By database analysis, Jang et al. (1996) revealed the existence of a Caenorhabditis elegans homolog, hypothetical protein F44b9, which has 35% amino acid identity to mouse Aup1. With numerous overlapping EST sequences, Jang et al. (1996) identified a human homolog of mouse Aup1. Spandl et al. (2011) reported that the 410-amino acid human AUP1 protein contains a long N-terminal hydrophobic stretch, followed by an acyltransferase domain, a coupling of ubiquitin to endoplasmic reticulum-associated degradation (CUE) domain, and a C-terminal G2 (UBE2G2; 603124)-binding region (G2BR). Immunofluorescence analysis of human and other mammalian cell lines localized AUP1 to the surface of lipid droplets and at the endoplasmic reticulum (ER).GENE FUNCTION
Using human cell lines, Mueller et al. (2008) identified several components of a protein complex required for retrotranslocation or dislocation of misfolded proteins from the ER lumen to the cytosol for proteasome-dependent degradation. These included SEL1L (602329), HRD1 (SYVN1; 608046), derlin-2 (DERL2; 610304), the ATPase p97 (VCP; 601023), PDI (P4HB; 176790), BIP (HSPA5; 138120), calnexin (CANX; 114217), AUP1, UBXD8 (FAF2), UBC6E (UBE2J1; 616175), and OS9 (609677). Using differential solubilization and protease digestion, Spandl et al. (2011) showed that the N-terminal hydrophobic stretch in the AUP1 protein formed a hairpin structure on the surface of lipid droplets, with both the N and C termini facing the cytoplasm. A soluble form of recombinant human AUP1 and the isolated G2BR domain bound the E2 ubiquitin conjugase Ube2g2, but not Ube2g1 (601569). Immunoaffinity chromatography confirmed the interaction between AUP1 and Ube2g2 and showed that AUP1 bound itself. Full-length AUP1 containing mutations or deletion of the G2BR domain did not bind Ube2g2. Spandl et al. (2011) hypothesized that AUP1 in lipid droplets, and perhaps at the ER, has a role in ubiquitin-mediated protein degradation by recruiting UBE2G2.MAPPING
By YAC contig analysis, Jang et al. (1996) mapped the human AUP1 gene to chromosome 2p13. ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 29, 2020: Protein entry updated
Automatic update: OMIM entry 602434 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).