NAD(P) transhydrogenase, mitochondrial (NNT)
The protein contains 1086 amino acids for an estimated molecular weight of 113896 Da.
The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane (By similarity). May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland (PubMed:22634753). (updated: July 31, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
Biological Process
Cell redox homeostasis
Cellular metabolic process
Cellular oxidant detoxification
NADPH regeneration
Negative regulation of apoptotic process
Negative regulation of protein phosphorylation
Oxidation-reduction process
Oxygen homeostasis
Positive regulation of hydrogen peroxide catabolic process
Positive regulation of mitochondrial membrane potential
Proton transmembrane transport
Proton transport
Reactive oxygen species metabolic process
Response to vitamin
Small molecule metabolic process
Tricarboxylic acid cycle
The reference OMIM entry for this protein is 607878
Nicotinamide nucleotide transhydrogenase; nnt
DESCRIPTION
NNT is a pyridine nucleotide transhydrogenase (EC 1.6.1.1). These integral inner mitochondrial membrane proteins are part of the energy-transfer system of the respiratory chain and catalyze the transfer of a hydride ion between nicotinamide adenine dinucleotide, NAD(H), and oxidized nicotinamide dinucleotide phosphate, NADP(H) (summary by Zieger and Ware, 1997).CLONING
Using bovine Nnt as probe, Arkblad et al. (1996) cloned NNT from a heart cDNA library, and they cloned mouse Nnt from a mouse liver cDNA library. The deduced 1,086-amino acid NNT protein has a 43-amino acid presequence, 10 membrane-spanning alpha helices, and substrate-binding sites for NAD(H) and NADP(H). It shares 97% amino acid identity with bovine Nnt and 94% identity with mouse Nnt. A hypervariable region is located in the first transmembrane helix, and the presequences are less conserved. Zieger and Ware (1997) cloned NNT from a cell line established from a solid tumor in a patient with megakaryoblastic leukemia. Meimaridou et al. (2012) found wide expression of NNT in humans, with expression most readily detectable in adrenal, heart, kidney, thyroid, and adipose tissues.MAPPING
By FISH, Arkblad et al. (1997) mapped the NNT gene to chromosome 5p13.1-cen. They mapped the mouse Nnt gene to chromosome 13D2.GENE FUNCTION
Meimaridou et al. (2012) studied the adrenal glands from Nnt-deficient mice and observed slightly disorganized zonae fasciculatae with higher levels of apoptosis than wildtype mice. There were no observable differences in the levels of the steroidogenic enzymes CYP11A1 (118485) and CYP11B1 (610613) between wildtype and mutant mice; however, the mutant mice did have lower basal and stimulated levels of corticosterone than their wildtype counterparts. Knockdown of NNT in the human adrenocortical H295R cell line by short hairpin RNA not only increased the levels of mitochondrial reactive oxygen species and apoptosis but also lowered the glutathione (GSH; see 601002)/glutathione disulfide (GSSG) ratio, implying that these cells also have impaired redox potential.MOLECULAR GENETICS
In 3 kindreds with glucocorticoid deficiency mapping to chromosome 5p13-q12 (GCCD4; 614736), Meimaridou et al. (2012) identified homozygosity for 3 different mutations in the NNT gene (607878.0001-607878.0003) that segregated with disease in each family and were not found in controls. Subsequent analysis of the NNT gene in 100 individuals with GCCD of unknown etiology revealed homozygosity or compound heterozygosity for 18 more mutations in 12 kindreds (see, e.g., 607878.0004-607878.0006). The mutations were spread throughout the NNT gene and included a mutation that destroyed the translation-initiating methionine, 2 additional splice site mutations, and many missense and nonsense changes. ... More on the omim web site
Aug. 20, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607878 was added.