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Characterization of the Gene EPAC2: Structure, Chromosomal Localization, Tissue Expression, and Identification of the Liver-Specific Isoform
Abstract
The liver-specific protein cAMP-GEFII (also known as Epac2) belongs to a family of cyclic adenosine monophosphate (cAMP) binding proteins having guanine nucleotide exchange factor (GEF) activity (the cAMP-GEF family). Here we clone the gene EPAC2, encoding cAMP-GEFII, from a human liver cDNA library. Human EPAC2 has at least 31 exons and is mapped to human chromosome 2q31. Analyses by primer extension, reverse transcriptase-polymerase chain reaction, and in situ hybridization revealed the presence of three transcription start sites of liver-specific Epac2: two major sites located in exon 10 and a minor site in intron 9. The same translation start site is used in all three transcripts. Liver-specific cAMP-GEFII protein, which lacks the first cAMP-binding domain and the Dishevelled/Egl-10/Pleckstrin domain, was detected at 79 kDa by immunoblot analysis, confirming the presence of the short form of cAMP-GEFII in the liver. Liver-specific cAMP-GEFII also has GEF activity toward Rap1. These results demonstrate the presence of liver-specific cAMP-GEFII. Together with the previous finding that cAMP-GEFII is responsible for cAMP-dependent exocytosis in secretory cells, our study suggests that cAMP-GEFII may have a distinct role in liver.
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“Several lines of evidence has conceived that EPAC2 plays significant roles in the liver45,71,96, endocrine glands and brain97–99.”
From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [96]
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Chen, J., Huang, H., Chen, C., Xia, G., Huang, H., Xiong, Y., Luo, P., Chen, Y., Li, J., Wen, L., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08818-x · Cited by 1
Metadata
- Authors
- Ueno, H., Shibasaki, T., Iwanaga, T., Takahashi, K., Yokoyama, Y., Liu, L.-M., Yokoi, N., Ozaki, N., Matsukura, S., Yano, H., & Seino, S.
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 78
- Issue
- 1-2
- Pages
- 91-98
- ISSN
- 0888-7543
- Cited by
- 58
- References
- 0
- Language
- en
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