Alternative titles; symbols
HGNC Approved Gene Symbol: CTDNEP1
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,243,591-7,251,978 (from NCBI)
CTDNEP1 is a phosphatase that forms a complex with the regulatory protein CNEP1R1 (616869) to activate lipin-1 (LPIN1; 605518) and lipin-2 (LPIN2; 605519) (Han et al., 2012).
Satow et al. (2002) cloned Xenopus Dullard and, by database analysis, identified its human homolog. The deduced 261-amino acid human protein shares 92% identity with Xenopus Dullard, and both have the conserved C-terminal domain of NLIIF (CTDSP1; 605323). In Xenopus embryos, Dullard mRNA localized to the animal hemisphere before the gastrula stage. It was restricted to the neural region as gastrulation proceeded and subsequently localized to the neural tissues, branchial arches, and pronephroi at the tail-bud stages.
Using immunofluorescence analysis, Han et al. (2012) showed that CTDNEP1 and NEP1R1 (CNEP1R1), the human orthologs of yeast Nem1 and Spo7, respectively, colocalized in the perinuclear area, in the nuclear rim, and in a filamentous pattern in the cytoplasm, likely the endoplasmic reticulum (ER), in transfected HeLa cells.
Hartz (2007) mapped the CTDNEP1 (DULLARD) gene to chromosome 17p13.1 based on an alignment of the CTDNEP1 sequence (GenBank AJ011916) with the genomic sequence (build 36.1).
By translational knockdown, Satow et al. (2002) found that Dullard was involved in neural development in Xenopus embryos. Overexpression of Dullard led to apoptosis in early Xenopus development.
Satow et al. (2006) found that Dullard negatively regulated BMP (see BMP1; 112264) signaling by promoting ubiquitin-mediated proteasomal degradation of BMP receptors (see BMPR2; 600799) in Xenopus. Dullard phosphatase activity was essential for degradation of BMP receptors and neural induction in Xenopus.
Han et al. (2012) found that cotransfection of human NEP1R1 and CTDNEP1 rescued neutral lipid synthesis defects, but not sporulation defects, in yeast mutants lacking both Spo7 and Nem1 in a CTDNEP1 phosphatase activity-dependent manner. Coimmunoprecipitation experiments demonstrated that human NEP1R1 interacted with and stabilized human CTDNEP1 in cotransfected yeast and HEK293 cells. In HEK293 cells, cotransfection of human NEP1R1 and CTDNEP1 led to increased nuclear, perinuclear, and nuclear rim accumulation of exogenous mouse lipin-1b. Lipin-1b also showed nuclear accumulation, but not perinuclear or nuclear rim accumulation, in cotransfected HeLa cells. Exogenously expressed human CTDNEP1 required NEP1R1 to dephosphorylate mouse lipin-1b, -1a, and -2 in HEK293 cells. Levels of Nep1r1 and Ctdnep1 mRNA were reduced in muscle and gonadal fat of Lpin1-null fatty liver dystrophy (fld) mice, suggesting coordinated regulation of these genes. Han et al. (2012) concluded that NEP1R1 and CTDNEP1 are functionally conserved from yeast to human and function in the lipid activation pathway.
Han et al. (2012) showed that RNA interference-mediated knockdown of Ctdnep1, Nep1r1, or Lpin1 in C. elegans embryos resulted in a distinctive 'twinned-nuclei' phenotype in each daughter cell.
Han, S., Bahmanyar, S., Zhang, P., Grishin, N., Oegema, K., Crooke, R., Graham, M., Reue, K., Dixon, J. E., Goodman, J. M. Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the metazoan Spo7p ortholog and functions in the lipin activation pathway. J. Biol. Chem. 287: 3123-3137, 2012. [PubMed: 22134922] [Full Text: https://doi.org/10.1074/jbc.M111.324350]
Hartz, P. A. Personal Communication. Baltimore, Md. 1/4/2007.
Satow, R., Chan, T., Asashima, M. Molecular cloning and characterization of dullard: a novel gene required for neural development. Biochem. Biophys. Res. Commun. 295: 85-91, 2002. [PubMed: 12083771] [Full Text: https://doi.org/10.1016/S0006-291X(02)00641-1]
Satow, R., Kurisaki, A., Chan, T., Hamazaki, T. S., Asashima, M. Dullard promotes degradation and dephosphorylation of BMP receptors and is required for neural induction. Dev. Cell 11: 763-774, 2006. [PubMed: 17141153] [Full Text: https://doi.org/10.1016/j.devcel.2006.10.001]