NAD(P)HX dehydratase is an enzyme that in humans is encoded by the NAXD gene (previously CARKD). The NAXD protein is a ATP-dependent NAD(P)H-hydrate dehydratase enzyme that is involved in repairing NAD(P)HX, a type of damaged NAD(P)H.
Gene
Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome: COL4A2: A2 Subunit of type IV collagen RAB20: Potential regulator of Connexin 43 trafficking. CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2 ING1: Tumor-Suppressor Protein
Tissue distribution
CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog, indicate its expression in almost all tissues. One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocytes. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.
Structure
This protein is part of the phosphomethylpyrimidine kinase: ribokinase / pfkB superfamily. This family is characterized by the presence of a domain shared by the family. CARKD contains a carbohydrate kinase domain (). This family is related to and implying that it also is a carbohydrate kinase.
Predicted properties
The following properties of CARKD were predicted using bioinformatic analysis: Molecular Weight: 41.4 KDal Isoelectric point: 9.377 CARKD orthologs have highly variable isoelectric points. Post-translational modification: Three post-translational modifications are predicted: Modified Phosphotyrosine Residue Two N-Linked Glycosylation Sites A Signal Peptide and signal peptide cleavage site was predicted.
Binding partners
The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD. This prediction is based on co-occurrence across genomes and co-expression. In addition to these data, the orthologs of CARKD in E. coli contain a domain similar to APOA1BP. This indicates that the two proteins are likely to have originated from a common evolutionary ancestor and, according to Rosetta stone analysis theory, are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.
Clinical significance
Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia. In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.
Mutations of the NAXD gene cause the rare disease early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2).
References
Further reading
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