Alternative titles; symbols
HGNC Approved Gene Symbol: ENC1
Cytogenetic location: 5q13.3 Genomic coordinates (GRCh38) : 5:74,627,409-74,640,728 (from NCBI)
DNA damage and/or hyperproliferative signals activate wildtype p53 tumor suppressor protein (TP53; 191170), inducing cell cycle arrest or apoptosis. Mutations that inactivate p53 occur in 50% of all tumors. Polyak et al. (1997) used serial analysis of gene expression (SAGE) to evaluate cellular mRNA levels in a colorectal cancer cell line transfected with p53. Of 7,202 transcripts identified, only 14 were expressed at levels more than 10-fold higher in p53-expressing cells than in control cells. Polyak et al. (1997) termed these genes 'p53-induced genes,' or PIGs, several of which were predicted to encode redox-controlling proteins. They noted that reactive oxygen species (ROS) are potent inducers of apoptosis. Flow cytometric analysis showed that p53 expression induces ROS production, which increases as apoptosis progresses under some conditions. The authors stated that the PIG10 gene, also called ENC1, encodes an actin-binding protein.
By screening fetal and adult hippocampus cDNA libraries using a brain development-related cDNA as the probe, Kim et al. (1998) obtained cDNAs encoding ENC1, which they called NRPB (nuclear-restricted protein/brain). Human and mouse ENC1 share 99% amino acid identity. The deduced 589-amino acid ENC1 protein has a 114-amino acid BTB/POZ-like domain in the alpha-helical N terminus and a beta sheet bearing a 50-amino acid 'kelch' motif repeated 6 times in the C terminus. The kelch motif invariably contains 2 adjacent glycine residues and shares homology with several actin-associated proteins, including the Drosophila kelch protein. Northern blot analysis detected abundant expression of a 5.5-kb ENC1 transcript in fetal brain, with moderate expression in fetal heart, lung, and kidney. In adult tissues, high levels of ENC1 were detected in brain, particularly in amygdala and hippocampus, and lower levels were detected in pancreas. In 12 day- but not 10 day-postcoitus mouse embryos, expression of Enc1 was 50-fold higher in brain than in other tissues. Immunoprecipitation and Western blot analysis showed that ENC1 is expressed as a 67-kD protein in nuclear pellets and as 67- and 57-kD proteins in total cell lysates from primary neurons. Western blot analysis, immunofluorescence, and confocal microscopy demonstrated that Enc1 is expressed in the nuclear matrix of rat hippocampal neurons but not at all in astrocytes.
By searching an EST database for homologs of mouse Enc1, Hernandez et al. (1998) identified human ENC1. Northern blot analysis detected abundant expression of an approximately 4.5-kb ENC1 transcript in brain, with lower expression in pancreas and no expression in other tissues. Within the central nervous system, expression was highest in cerebral cortex, frontal and temporal lobes, putamen, and spinal cord; lower expression was found in medulla and cerebellum, and very low levels of expression were found in the occipital pole. Low levels of ENC1 were also detected in a variety of neural tumor cell lines. ENC1 expression increased dramatically in a neuroblastoma cell line undergoing retinoic acid-induced differentiation.
By differential display, Zhao et al. (2000) identified rat Enc1 as a transcript associated with differentiation of rat preadipocytes in primary culture. Using the fragment identified by differential display as probe, they cloned full-length Enc1 cDNA from a mouse brain cDNA library. By Northern blot analysis of rat tissues, Zhao et al. (2000) found high expression in brain, low expression in testis, and no expression in other tissues tested. They also found high expression of Enc1 in the stroma-vascular fraction of adipose tissue but very little in mature adipocyte fraction. Transient transfection in a 3T3 fibroblastic preadipocyte cell line resulted in subcellular colocalization with F-actin (102560).
Kim et al. (1998) showed that expression of ENC1 induced neuronal process formation, whereas antisense treatment inhibited neurite development. Immunoblot analysis showed that ENC1 can be phosphorylated and binds to the functionally active hypophosphorylated form of the nuclear matrix protein RB1 (614041) during neuronal differentiation.
Using primary cell culture of rat stroma-vascular cells, Zhao et al. (2000) found that transient early expression of Enc1 preceded the conversion of the fibroblastic preadipocytes to mature adipose. Enc1 expression also preceded expression of adipocyte-specific markers, including transcription factors known to activate adipocyte genes. Antisense transfection blocked differentiation to the mature adipocyte morphology.
Alterations in chromosome 5q13 are a frequent finding in hairy cell leukemia (HCL). Hammarsund et al. (2004) reported that a 5q13.3 breakpoint discovered in an HCL patient disrupted a conserved alternative isoform of beta-hexosaminidase (HEXB; 606873). This isoform directly overlapped, in a cis-antisense fashion, exon 1 of ENC1, and was thus named ENC1AS. Purified HCL tumor cells from 26 HCL patients showed striking upregulation of ENC1 in all 26 samples analyzed. Hammarsund et al. (2004) identified a complex 5-prime regulatory mechanism involving an inverse expression of the ENC1 and the ENC1AS transcripts in several tissues, suggesting that expression of ENC1AS may regulate ENC1 levels.
Hammarsund et al. (2004) noted that the ENC1 gene contains 3 exons spanning approximately 13.3 kb.
Hernandez et al. (1999) mapped the human ENC1 gene to chromosome 5q13 by FISH. Hernandez et al. (2000) mapped the mouse homolog to chromosome 13D1 by FISH.
Hammarsund, M., Lerner, M., Zhu, C., Merup, M., Jansson, M., Gahrton, G., Kluin-Nelemans, H., Einhorn, S., Grander, D., Sangfelt, O., Corcoran, M. Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and identification of ENC-1 overexpression in hairy cell leukemia. Hum. Molec. Genet. 13: 2925-2936, 2004. [PubMed: 15459180] [Full Text: https://doi.org/10.1093/hmg/ddh315]
Hernandez, M.-C., Andres-Barquin, P. J., Holt, I., Israel, M. A. Cloning of human ENC-1 and evaluation of its expression and regulation in nervous system tumors. Exp. Cell Res. 242: 470-477, 1998. [PubMed: 9683534] [Full Text: https://doi.org/10.1006/excr.1998.4109]
Hernandez, M.-C., Andres-Barquin, P. J., Israel, M. A. Assignment of the ectodermal-neural cortex 1 gene (Enc1) to mouse chromosome band 13D1 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 89: 158-159, 2000. [PubMed: 10965111] [Full Text: https://doi.org/10.1159/000015601]
Hernandez, M.-C., Andres-Barquin, P. J., Kuo, W. L., Israel, M. A. Assignment of the ectodermal-neural cortex 1 gene (ENC1) to human chromosome band 5q13 by in situ hybridization. Cytogenet. Cell Genet. 87: 89-90, 1999. [PubMed: 10640818] [Full Text: https://doi.org/10.1159/000015398]
Kim, T.-A., Lim, J., Ota, S., Raja, S., Rogers, R., Rivnay, B., Avraham, H., Avraham, S. NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation. J. Cell Biol. 141: 553-566, 1998. [PubMed: 9566959] [Full Text: https://doi.org/10.1083/jcb.141.3.553]
Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W., Vogelstein, B. A model for p53-induced apoptosis. Nature 389: 300-305, 1997. [PubMed: 9305847] [Full Text: https://doi.org/10.1038/38525]
Zhao, L., Gregoire, F., Sul, H. S. Transient induction of ENC-1, a kelch-related actin-binding protein, is required for adipocyte differentiation. J. Biol. Chem. 275: 16845-16850, 2000. [PubMed: 10828068] [Full Text: https://doi.org/10.1074/jbc.275.22.16845]