NAD kinase 2, mitochondrial (NADK2)
The protein contains 442 amino acids for an estimated molecular weight of 49433 Da.
Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. (updated: July 24, 2007)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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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The reference OMIM entry for this protein is 615787
Nad kinase 2, mitochondrial; nadk2
Chromosome 5 open reading frame 33; c5orf33
DESCRIPTION
NADK2 is a mitochondrial kinase that synthesizes NADP+ (Ohashi et al., 2012).CLONING
Using Arabidopsis Nadk3 to query a human database, Ohashi et al. (2012) identified 2 splice variants of NADK2, which they called C5ORF33. The deduced full-length 442-amino acid protein has a 62-amino acid N-terminal mitochondrial targeting signal and a central NADK domain. Variant 2 encodes a deduced 279-amino acid protein that is N-terminally truncated relative to full-length NADK2. Quantitative PCR detected variable NADK2 expression in all 12 human tissues examined, with highest expression in heart, liver, and testis. Fluorescence-tagged NADK2 localized to mitochondria in transfected HEK293A cells. Cell fractionation followed by Western blot analysis confirmed that NADK2 localized to mitochondria.GENE FUNCTION
Using recombinant protein expressed in E. coli, Ohashi et al. (2012) found that soluble NADK2 lacking the mitochondrial localization signal converted NAD and ATP to NADP+ and ADP. NADK2 also used several endogenous polyphosphates as phosphoryl donors. NADK2 did not function as a kinase with other substrates tested. NADK2 activity was inhibited by NADP+, NADH, and NADPH. Knockdown of NADK2 in HEK293A cells did not affect cell viability or mitochondrial morphology, but it decreased mitochondrial NADK activity and increased intracellular reactive oxygen species.MAPPING
Hartz (2014) mapped the NADK2 gene to chromosome 5p13.2 based on an alignment of the NADK2 sequence (GenBank GENBANK AK057950) with the genomic sequence (GRCh37).MOLECULAR GENETICS
In a Hispanic boy with 2,4-dienoyl-CoA reductase deficiency (DECRD; 616034), Houten et al. (2014) identified a homozygous nonsense mutation in the NADK2 gene (R340X; 615787.0001). The mutation was found by exome sequencing and segregated with the disorder in the family. Mitochondria isolated from patient fibroblasts showed decreased levels of NADP(H). Although NADPH did not restore DECR activity in patient cells, transfection of wildtype NADK2 was able to rescue the DECR deficiency. A mitochondrial stress test indicated overall decreased oxygen consumption and increased extracellular acidification in patient cells compared to controls. The patient presented in early infancy with a severe encephalopathy, developmental delay, movement abnormalities, and lactic acidosis; he died at age 5 years. Laboratory studies showed decreased activity of DECR and hyperlysinemia due to impaired activity of AASS (605113), both of which are dependent upon mitochondrial NADP(H), but Houten et al. (2014) suggested that the severe phenotype likely resulted from impairment of additional mitochondrial NADP-dependent processes. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615787 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).