Kinase Subfamily NDKE
NDKB is a subfamily of Nucleoside Diphosphate Kinases. It contains two human genes, NME8 and NME9. Both encode thioredoxin domains in addition to dual nucleoside diphosphate domains.
NDKE are found in most holozoa, and in two basal fungi (Batrachochytrium dendrobatidis, which has a similar domain architecture, but with four NDK catalytic domains (gi|575480492), and Rozella allomycis (gi|528893406). They are absent in nematodes, and have at best a trace in arthropods - a protein with the thioredoxin domain and a long C-terminal extension, but no detectible homology to NDKE, known as CG14221 or CG18130 in Drosophila. The losses in nematodes, most fungi, and degeneration in arthropods parallels the losses of cilia in these organisms.
A single NDKE, NME8 is seen in most vertebrates. All mammals have an additional NDKE, called NME9, which is truncated directly after the first kinase domain.
NDKE typically have a thioredoxin domain followed by three NDK domains of the NDKE subfamily. The catalytic H of the first domain is lost in amniotes, and the catalytic H of the second domain is also lost in primates and rodents.
NDKE appear to be involved in cilium biology. Members from the invertebrate Ciona intestinalis and the sea urchin are both intermediate chains of the flagellar outer arm dynein . Mutations in NME8 in human are linked to primary ciliary dyskinesia (PCD), a disease caused by axonemal defects, and also linked to dynein and cilium biology . NME8 is largely testis-specific (http://www.gtexportal.org/home/gene/NME8) and , though the PCD suggests broader expression during development , while NME9 is also expressed at a low level in brain and scattered other tissues (http://www.gtexportal.org/home/gene/NME9), including lung [4, 5]. Bacterially-expressed NME8 was seen not to have kinase or thioredoxin activity . The Drosophila putative NDKE, CG18130 was implicated in hearing, along with various dynein genes and other ciliary components  and both CG14221 and CG18130 were shown to be part of the sperm proteome .
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