HGNC Approved Gene Symbol: AUP1
Cytogenetic location: 2p13.1 Genomic coordinates (GRCh38): 2:74,526,652-74,529,706 (from NCBI)
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).
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.
By YAC contig analysis, Jang et al. (1996) mapped the human AUP1 gene to chromosome 2p13.
Jang, W., Weber, J. S., Bashir, R., Bushby, K., Meisler, M. H. Aup1, a novel gene on mouse chromosome 6 and human chromosome 2p13. Genomics 36: 366-368, 1996. [PubMed: 8812468] [Full Text: https://doi.org/10.1006/geno.1996.0477]
Mueller, B., Klemm, E. J., Spooner, E., Claessen, J. H., Ploegh, H. L. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc. Nat. Acad. Sci. 105: 12325-12330, 2008. [PubMed: 18711132] [Full Text: https://doi.org/10.1073/pnas.0805371105]
Spandl, J., Lohmann, D., Kuerschner, L., Moessinger, C., Thiele, C. Ancient ubiquitous protein 1 (AUP1) localizes to lipid droplets and binds the E2 ubiquitin conjugase G2 (Ube2g2) via its G2 binding region. J. Biol. Chem. 286: 5599-5606, 2011. [PubMed: 21127063] [Full Text: https://doi.org/10.1074/jbc.M110.190785]