Kinase Subfamily NDKE
Kinase Classification: Group NDK: 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.
Evolution
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.
Domain Structure
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.
Functions
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 [1]. 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 [2]. NME8 is largely testis-specific (http://www.gtexportal.org/home/gene/NME8) and [3], 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 [3]. The Drosophila putative NDKE, CG18130 was implicated in hearing, along with various dynein genes and other ciliary components [6] and both CG14221 and CG18130 were shown to be part of the sperm proteome [7].
References
- Padma P, Hozumi A, Ogawa K, and Inaba K. Molecular cloning and characterization of a thioredoxin/nucleoside diphosphate kinase related dynein intermediate chain from the ascidian, Ciona intestinalis. Gene. 2001 Sep 5;275(1):177-83. DOI:10.1016/s0378-1119(01)00661-8 |
- Duriez B, Duquesnoy P, Escudier E, Bridoux AM, Escalier D, Rayet I, Marcos E, Vojtek AM, Bercher JF, and Amselem S. A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3336-41. DOI:10.1073/pnas.0611405104 |
- Sadek CM, Damdimopoulos AE, Pelto-Huikko M, Gustafsson JA, Spyrou G, and Miranda-Vizuete A. Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly repeated NDP-kinase domains is expressed in human testis germ cells. Genes Cells. 2001 Dec;6(12):1077-90. DOI:10.1046/j.1365-2443.2001.00484.x |
- Lee EJ, In KH, Kim JH, Lee SY, Shin C, Shim JJ, Kang KH, Yoo SH, Kim CH, Kim HK, Lee SH, and Uhm CS. Proteomic analysis in lung tissue of smokers and COPD patients. Chest. 2009 Feb;135(2):344-352. DOI:10.1378/chest.08-1583 |
- Miranda-Vizuete A, Sadek CM, Jiménez A, Krause WJ, Sutovsky P, and Oko R. The mammalian testis-specific thioredoxin system. Antioxid Redox Signal. 2004 Feb;6(1):25-40. DOI:10.1089/152308604771978327 |
- Senthilan PR, Piepenbrock D, Ovezmyradov G, Nadrowski B, Bechstedt S, Pauls S, Winkler M, Möbius W, Howard J, and Göpfert MC. Drosophila auditory organ genes and genetic hearing defects. Cell. 2012 Aug 31;150(5):1042-54. DOI:10.1016/j.cell.2012.06.043 |
- Dorus S, Busby SA, Gerike U, Shabanowitz J, Hunt DF, and Karr TL. Genomic and functional evolution of the Drosophila melanogaster sperm proteome. Nat Genet. 2006 Dec;38(12):1440-5. DOI:10.1038/ng1915 |
