ATP-dependent (S)-NAD(P)H-hydrate dehydratase (NAXD)

The protein contains 347 amino acids for an estimated molecular weight of 36576 Da.

 

Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 21

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VariantDescription
dbSNP:rs3742191
dbSNP:rs3742192
dbSNP:rs1044112
PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent N
PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent N

The reference OMIM entry for this protein is 615910

Carbohydrate kinase domain-containing protein; carkd
(s)-nadph-hydrate dehydratase, atp-dependent

DESCRIPTION

Hydrated forms of NADH and NADPH, called NADHX and NADPHX, respectively, inhibit several dehydrogenases. The (S)-epimer of these damaged cofactors can be reconverted to the active form by CARKD, an ATP-dependent dehydratase (EC 4.2.1.93). The (R)-epimers require epimerization to the (S)-form prior to dehydration by CARKD (summary by Marbaix et al., 2014).

CLONING

Marbaix et al. (2014) identified 3 alternative initiating ATG codons in mouse, rat, and human CARKD, the second of which becomes available following alternative splicing at the 3-prime end of exon 1. Proteins translated from the first ATG have an N-terminal mitochondrial targeting signal (mCARKD), those translated from the second were predicted to have a signal peptide (spCARKD), and those translated from the third were predicted to have no N-terminal targeting signal and were likely cytosolic (cCARKD). Following expression in Chinese hamster ovary cells, fluorescence-tagged mouse mCarkd was expressed predominantly in mitochondria, whereas spCarkd localized to nuclear membranes and the endoplasmic reticulum, and cCarkd showed a diffuse cytosolic localization. Deglycosylation reduced the apparent molecular mass of spCarkd, but not cCarkd, by Western blot analysis.

GENE FUNCTION

Marbaix et al. (2014) showed that recombinant mouse Carkd dehydrated (S)-NADPHX to (S)-NADPH in vitro in the presence of MgCl(2) and ATP.

GENE STRUCTURE

Marbaix et al. (2014) determined that the CARKD gene contains 10 exons and spans 5 kb. Exon 1 contains 2 putative initiator ATG codons, and exon 2 contains a third initiator ATG. The 3-prime end of exon 1 is subject to alternative splicing.

MAPPING

Hartz (2014) mapped the CARKD gene to chromosome 13q34 based on an alignment of the CARKD sequence (GenBank GENBANK AF091088) with the genomic sequence (GRCh38). ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615910 was added.

Feb. 22, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 22, 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).