PEG10 explained

Retrotransposon-derived protein PEG10 is a protein that in humans is encoded by the PEG10 gene.^{[1] [2] [3] [4]}

Function

This gene includes two overlapping reading frames of the same transcript encoding distinct isoforms. The shorter isoform has a CCHC-type zinc finger motif containing a sequence characteristic of gag proteins of most retroviruses and some retrotransposons, and it functions in part by interacting with members of the TGF-beta receptor family. The longer isoform has the active-site DSG consensus sequence of the protease domain of pol proteins. The longer isoform is the result of -1 translational frameshifting that is also seen in some retroviruses. Expression of these two isoforms only comes from the paternal allele due to imprinting. Increased gene expression (as observed by an increase in mRNA levels) is associated with hepatocellular carcinomas.^[4]

PEG10 is a paternally expressed imprinted gene that is expressed in adult and embryonic tissues.^[5] Most notable expression occurs in the placenta. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC). This gene has been reported to play a role in cell proliferation, differentiation and apoptosis. Overexpression of this gene has been associated with several malignancies, such as hepatocellular carcinoma and B-cell lymphocytic leukemia. Knockout mice lacking this gene showed early embryonic lethality with placental defects, indicating the importance of this gene in embryonic development. In preeclampsia placental tissue, PEG10 has been shown to be downregulated^[6] and upregulated^[7] implicating it as a possible causal role in the occurrence of preeclampsia.

Interactions

PEG10 has been shown to interact with SIAH2^[8] and SIAH1.^[8]

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 3 . 197–205 . Jun 1999 . 10470851 . 10.1093/dnares/6.3.197 . free .
• Volff J, Körting C, Schartl M . Ty3/Gypsy retrotransposon fossils in mammalian genomes: did they evolve into new cellular functions? . Molecular Biology and Evolution . 18 . 2 . 266–70 . Feb 2001 . 11158386 . 10.1093/oxfordjournals.molbev.a003801 . free .
• Shigemoto K, Brennan J, Walls E, Watson CJ, Stott D, Rigby PW, Reith AD . Identification and characterisation of a developmentally regulated mammalian gene that utilises -1 programmed ribosomal frameshifting . Nucleic Acids Research . 29 . 19 . 4079–88 . Oct 2001 . 11574691 . 60235 . 10.1093/nar/29.19.4079 .
• Smallwood A, Papageorghiou A, Nicolaides K, Alley MK, Jim A, Nargund G, Ojha K, Campbell S, Banerjee S . Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta . Biology of Reproduction . 69 . 1 . 286–93 . Jul 2003 . 12620933 . 10.1095/biolreprod.102.013078 . free .
• Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y . Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 . Cancer Research . 63 . 12 . 3043–8 . Jun 2003 . 12810624 .
• Tsou AP, Chuang YC, Su JY, Yang CW, Liao YL, Liu WK, Chiu JH, Chou CK . Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers . Journal of Biomedical Science . 10 . 6 Pt 1 . 625–35 . 2004 . 14576465 . 10.1159/000073528 . 202655065 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Lux A, Beil C, Majety M, Barron S, Gallione CJ, Kuhn HM, Berg JN, Kioschis P, Marchuk DA, Hafner M . Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1 . The Journal of Biological Chemistry . 280 . 9 . 8482–93 . Mar 2005 . 15611116 . 10.1074/jbc.M409197200 . free .
• Manktelow E, Shigemoto K, Brierley I . Characterization of the frameshift signal of Edr, a mammalian example of programmed -1 ribosomal frameshifting . Nucleic Acids Research . 33 . 5 . 1553–63 . 2005 . 15767280 . 1065257 . 10.1093/nar/gki299 .
• He H, Olesnanik K, Nagy R, Liyanarachchi S, Prasad ML, Stratakis CA, Kloos RT, de la Chapelle A . Allelic variation in gene expression in thyroid tissue . Thyroid . 15 . 7 . 660–7 . Jul 2005 . 16053381 . 10.1089/thy.2005.15.660 .
• Hu C, Xiong J, Zhang L, Huang B, Zhang Q, Li Q, Yang M, Wu Y, Wu Q, Shen Q, Gao Q, Zhang K, Sun Z, Liu J, Jin Y, Tan J . PEG10 activation by co-stimulation of CXCR5 and CCR7 essentially contributes to resistance to apoptosis in CD19+CD34+ B cells from patients with B cell lineage acute and chronic lymphocytic leukemia . Cellular & Molecular Immunology . 1 . 4 . 280–94 . Aug 2004 . 16225771 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . Jan 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Li CM, Margolin AA, Salas M, Memeo L, Mansukhani M, Hibshoosh H, Szabolcs M, Klinakis A, Tycko B . PEG10 is a c-MYC target gene in cancer cells . Cancer Research . 66 . 2 . 665–72 . Jan 2006 . 16423995 . 10.1158/0008-5472.CAN-05-1553 . free .

Notes and References

1. Ono R, Kobayashi S, Wagatsuma H, Aisaka K, Kohda T, Kaneko-Ishino T, Ishino F . A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21 . Genomics . 73 . 2 . 232–7 . Apr 2001 . 11318613 . 10.1006/geno.2001.6494 .
2. Brandt J, Schrauth S, Veith AM, Froschauer A, Haneke T, Schultheis C, Gessler M, Leimeister C, Volff JN . Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals . Gene . 345 . 1 . 101–11 . Jan 2005 . 15716091 . 10.1016/j.gene.2004.11.022 .
3. Brandt J, Veith AM, Volff JN . A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes . Cytogenetic and Genome Research . 110 . 1–4 . 307–17 . Aug 2005 . 16093683 . 10.1159/000084963 . 38398479 .
4. Web site: Entrez Gene: PEG10 paternally expressed 10.
5. Web site: PEG10 paternally expressed 10 [Homo sapiens (human) ]]. Pubmed. 14 April 2015.
6. Liang XY, Chen X, Jin YZ, Chen XO, Chen QZ . Expression and significance of the imprinted gene PEG10 in placenta of patients with preeclampsia . Genetics and Molecular Research . 13 . 4 . Dec 18, 2014 . 10.4238/2014.December.18.2 . 25526181 . 10607–14. free .
7. Chen H, Sun M, Zhao G, Liu J, Gao W, Si S, Meng T . Elevated expression of PEG10 in human placentas from preeclamptic pregnancies . Acta Histochemica . 114 . 6 . Oct 2012 . 10.1016/j.acthis.2011.11.003 . 22137777 . 589–93.
8. Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y . Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1 . Cancer Research . 63 . 12 . 3043–8 . Jun 2003 . 12810624 .