NAD(P)H-hydrate epimerase (NAXE)
The protein contains 288 amino acids for an estimated molecular weight of 31675 Da.
Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. Accelerates cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis (PubMed:23719382). (updated: Aug. 12, 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs7516274 | |
| PEBEL1 | |
| PEBEL1 |
Biological Process
Lipid transport
Membrane raft distribution
NAD biosynthesis via nicotinamide riboside salvage pathway
Negative regulation of angiogenesis
Nicotinamide nucleotide metabolic process
Regulation of cholesterol efflux
Sprouting angiogenesis
The reference OMIM entry for this protein is 608862
Apolipoprotein a-i-binding protein; apoa1bp
Apoa-i-binding protein; aibp
Apoa1-binding protein
DESCRIPTION
APOA1BP interacts with apolipoprotein A-I (APOA1; 107680) and is involved in cholesterol transfer. It is also predicted to function as an epimerase in the repair of (R)-epimers of hydrated NADH and NADPH (summary by Marbaix et al., 2014).CLONING
Using the mature APOA1 protein (107680) as bait in a yeast 2-hybrid screen of a liver cDNA library, Ritter et al. (2002) cloned full-length APOA1BP, which they designated AIBP. The deduced 288-amino acid protein has a calculated molecular mass of 31.6 kD. APOA1BP contains an N-terminal signal peptide for translocation into the endoplasmic reticulum, a putative signal sequence cleavage site, and several putative phosphorylation and O-glycosylation sites. The processed mature protein has a calculated molecular mass of 29.1 kD. Human APOA1BP shares 88.2 to 89.5% amino acid identity with mouse, bovine, and porcine Apoa1bp. RNA dot blot analysis revealed abundant APOA1BP expression in all adult and fetal tissues investigated. Highest expression was in kidney, apex of heart, liver, thyroid gland, adrenal gland, and testis. APOA1BP was also expressed in all cell lines examined. Western blot analysis detected a 29-kD APOA1BP protein in hepatoma cell lysates and, to a lesser extent, in the culture medium. APOA1BP was also detected in cerebrospinal fluid (CSF) and urine of healthy volunteers, but not in normal serum samples. One of 3 patients with septic syndromes showed detectable serum APOA1BP. In sepsis serum and normal CSF, APOA1BP migrated as a complex with an apparent molecular mass of about 80 kD; no 29-kD monomeric APOA1BP was detected. Marbaix et al. (2014) identified 2 highly conserved methionines separated by approximately 50 residues at the N terminus of mouse and human AIBP. EST database analysis revealed that both were used as initiation methionines. The longer protein was predicted to be targeted to mitochondria, and the shorter protein was predicted to be cytosolic. The long and short isoforms of mouse Aibp were expressed in mitochondria and cytosol, respectively, following transfection of Chinese hamster ovary cells.GENE FUNCTION
Ritter et al. (2002) confirmed direct binding between APOA1 and APOA1BP by in vitro protein binding assays and copurification of the 2 proteins from hepatoma cell lysates. APOA1BP also bound APOA2 (107670) and high density lipoprotein (HDL). Stimulation of a human proximal tubular cell line with APOA1 and HDL resulted in secretion of APOA1BP in a dose-dependent manner. Secretion of APOA1BP was not increased in colon carcinoma or hepatoma cell lines following stimulation. Individuals with impaired renal function, as well as mice with resorption deficiency due to a megalin (600073) mutation, showed increased excretion of APOA1BP, indicating that APOA1BP is a reabsorbed protein. Fang et al. (2013) showed that AIBP accelerates cholesterol efflux from endothelial cells to HDL and thereby regulates angiogenesis. AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (191306) dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Notably, Aibp, a zebrafish homolog of human AIBP, regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell-autonomous regulator of angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, whereas forced Aibp expression inhibits an ... More on the omim web siteAug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 608862 was added.
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).