Alternative titles; symbols
HGNC Approved Gene Symbol: EDN2
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38): 1:41,478,775-41,484,683 (from NCBI)
The human endothelins represent a gene family composed of endothelin-1 (131240), endothelin-2, and endothelin-3 (131242). Based on the deduced amino acid sequences of the cloned ET2 and ET3 genes, corresponding proteins have been chemically synthesized and their vasoconstrictor activities studied. Of the 3 isopeptides, ET-2 has the most potent vasoconstrictor activity (summary by Ohkubo et al., 1990).
Ohkubo et al. (1990) cloned cDNAs encoding human ET-2 precursor from a cDNA library constructed with mRNA derived from the human renal adenocarcinoma cell line, ACHN, which specifically secretes immunoreactive ET-2. The cDNA was found to contain 1.3 kb and to encode the preproprotein consisting of 178 amino acid residues. Northern blot analysis of mRNA suggested that the transcript was 1.4 kb.
Bloch et al. (1991) used a cDNA clone for endothelin-2 to map the EDN2 gene to chromosome 1pter-p21 in human-mouse somatic cell hybrids. Southern blot hybridization demonstrated a single gene in both the human and the rat genome. Bloch et al. (1991) cloned the rat gene; the rat peptide differed from the human peptide at only 1 of 21 residues and was identical to mouse vasoactive intestinal contractor peptide (VIC). They concluded, therefore, that VIC is the mouse and rat analog of the human EDN2 gene. By Southern blot analysis of somatic cell hybrid DNAs and by in situ hybridization, Arinami et al. (1991) confirmed the assignment of EDN2 to chromosome 1 and regionalized it to 1p34.
Deng et al. (1994) found in the rat that the endothelin-2 gene is located on chromosome 5 and cosegregates strongly with systolic blood pressure in an F2 population derived from a cross of the Dahl salt-sensitive rat and the Lewis rat. Thus, ET2 is a quantitative trait locus (QTL) for blood pressure in the rat. ET1, ET3, and endothelin receptor type A (ETA; 131243) in the rat did not cosegregate with blood pressure in the several F2 populations tested.
Chang et al. (2013) identified transcription factor NFIB (600728) as an unanticipated coordinator of stem cell behavior in the hair follicle. Hair follicle stem cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair graying typical of melanocyte stem cell differentiation mutants. Furthermore, Chang et al. (2013) pinpointed KIT ligand (184745) as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin immunoprecipitation with high-throughput sequencing and transcriptional profiling, Chang et al. (2013) identified EDN2 as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulated Nfib-deficiency phenotypes in wildtype mice. Conversely, endothelin receptor (see 131244) antagonists and/or Kit blocking antibodies prevented precocious melanocyte stem cell differentiation in the Nfib-deficient niche. Chang et al. (2013) concluded that their findings revealed how melanocytes and hair follicle stem cell behaviors maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in injury, stress, and disease states.
Arinami, T., Ishikawa, M., Inoue, A., Yanagisawa, M., Masaki, T., Yoshida, M. C., Hamaguchi, H. Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3. Am. J. Hum. Genet. 48: 990-996, 1991. [PubMed: 2018043]
Bloch, K. D., Hong, C. C., Eddy, R. L., Shows, T. B., Quertermous, T. cDNA cloning and chromosomal assignment of the endothelin 2 gene: vasoactive intestinal contractor peptide is rat endothelin 2. Genomics 10: 236-242, 1991. [PubMed: 1840558] [Full Text: https://doi.org/10.1016/0888-7543(91)90505-9]
Chang, C.-Y., Pasolli, H. A., Giannopoulou, E. G., Gausch, G., Gronostajski, R. M., Elemento, O., Fuchs, E. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature 495: 98-102, 2013. [PubMed: 23389444] [Full Text: https://doi.org/10.1038/nature11847]
Deng, A. Y., Dene, H., Pravenec, M., Rapp, J. P. Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes. J. Clin. Invest. 93: 2701-2709, 1994. [PubMed: 8201007] [Full Text: https://doi.org/10.1172/JCI117284]
Ohkubo, S., Ogi, K., Hosoya, M., Matsumoto, H., Suzuki, N., Kimura, C., Onda, H., Fujino, M. Specific expression of human endothelin-2 (ET-2) gene in a renal adenocarcinoma cell line: molecular cloning of cDNA encoding the precursor of ET-2 and its characterization. FEBS Lett. 274: 136-140, 1990. [PubMed: 1701397] [Full Text: https://doi.org/10.1016/0014-5793(90)81348-r]