Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PEG10 (paternally expressed 10)

Written2011-02Andreas Lux
Institute of Molecular, Cell Biology, Mannheim University of Applied Sciences, Mannheim, Germany

(Note : for Links provided by Atlas : click)


HGNC (Hugo) PEG10
HGNC Alias symbKIAA1051
HGNC Alias nameSushi-Ichi retrotransposon homolog 1
 mammalian retrotransposon-derived 2
 retrotransposon Gag like 2
LocusID (NCBI) 23089
Atlas_Id 44104
Location 7q21.3  [Link to chromosome band 7q21]
Location_base_pair Starts at 94656325 and ends at 94669694 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PEG10.png]
Local_order Located next to the sarcoglycan epsilon gene SGCE in a head-to-head orientation. The transcription start sites of these two genes are separated by 130 bp. Both genes belong to a maternally imprinted gene cluster in humans as well as in the syntenic chromosomal regions of several other mammalian species and are expressed from the paternal allele.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ADAM29 (4q34.1)::PEG10 (7q21.3)FHIT (3p14.2)::PEG10 (7q21.3)GLTSCR1L (6p21.1)::PEG10 (7q21.3)
HBA2 (16p13.3)::PEG10 (7q21.3)L3MBTL2 (22q13.2)::PEG10 (7q21.3)PEG10 (7q21.3)::CLU (8p21.1)
PEG10 (7q21.3)::EIF3D (22q12.3)PEG10 (7q21.3)::PEG10 (7q21.3)RPLP0P2 (11q12.2)::PEG10 (7q21.3)
RPLP2 (11p15.5)::PEG10 (7q21.3)


  Figure 1. PEG10 splice variants PEG10-A and PEG10-B. Shown is the sequence around the splice junctions for the two PEG10 splice variants. The different start codons, translation initiation sites (TIS), in exon 1 and 2 are in red and underlined.
Note [Annexed document]
  Figure 2. Protein isoforms of human PEG10.
Description The PEG10 gene is comprised of two exons separated by a 6753 bp long intron for transcript variant 1 (PEG10-A) or by a 6742 bp long intron for transcript variant 2 (PEG10-B). Transcript variant 2 is the result of alternative splicing where splicing occurs 11 nucleotides after the major splice site of exon 1 (Lux et al., 2010) (see also figure 1). PEG10-A, has a length of 6573 bp and PEG10-B of 6584 bp. The analysis of four different cell lines (HepG2, HEK293, HL60 and SH-SY5Y) suggest that variant 1 is the major transcript. How alternative splicing for PEG10 is regulated and why two alternative splice products exist in parallel is not known.
Transcription The major transcription start site (mTSS) was determined to be at position 19.519.958 of reference sequence NT_007933|Hs7_8090 (Lux et al., 2010). This TSS is preceded by a typical TATA-box element in the ideal distance of 24-30 nucleotides. It appears as if there is at least one additional may be cell type dependent but less frequently used TSS further upstream. Several studies attempted to analyse the PEG10 promoter and how PEG10 expression is regulated but the results of these studies do not provide a coherent picture. For example, it was reported that c-MYC upregulates PEG10 expression in pancreatic and hepatic carcinoma cells as well as in a B-lymphocyte cell line (Li et al., 2006). This effect appears to be mediated by c-MYC binding to an E-box sequence in the proximal region of the PEG10 intron, thereby influencing PEG10 promoter activity. In reporter assays, analysing just the promoter sequence upstream of the mTSS, overexpression of c-MYC showed an inhibitory effect (Lux et al., 2010). By bioinformatic analysis of the PEG10 promoter region +1 to -220, binding sites for transcription factors like TBP, Sp1 or E2F were identified (Lux et al., 2010). Binding of E2F members E2F-1 and E2F-4 to this region was experimentally proven and it was demonstrated that both factors positively regulate PEG10 expression (Wang C et al., 2008). A previous report showed that PEG10 expression is also positively regulated by E2F-2 and E2F-3 in the U2OS osteosarcoma cell line (Müller et al., 2001). These data suggest that PEG10 expression can be controled by the E2F/Rb pathway that involves the cyclin D/CDK4 complex, which phosphorylates pocket proteins like the retinoblastoma protein Rb and releases E2Fs. Thus, it can be expected that overexpression of cyclin D and CDK4 does also increase PEG10 expression, which indeed is the case (Wang C et al., 2008). In contrast, the presence of TGF-beta leads to a dephosphorylation of Rb, therefore repressing the expression of E2F target genes like PEG10 (Wang C et al., 2008). The repressive activity of TGF-beta on PEG10 expression is in agreement with our own unpublished results with PEG10 promoter-reporter constructs. Previous results showed that the PEG10-RF1 protein inhibits TGF-beta3 signalling in a TGF-beta-specific luciferase reporter assay (Lux et al., 2005), may be representing a self-protecting mechanism from down-regulation. Furthermore, it was reported that increased PEG10 expression is subjected to hormonal regulation by the male hormon androgen (Jie et al., 2007). In this study, three androgen receptor binding sites (ARE) were identified for PEG10. Two sites were reported for exon 2 and one for the promoter region. Unfortunately, no exact specifications were given about these sites. However, using the in the publication given primer sets for a Blast search against the PEG10 sequence reveals that ARE-1 is not located in the promoter but in exon 1. Therefore, all three PEG10-specific ARE sites are distal to the promoter.

Transcript processing. Northern blot analyses have shown that for humans depending on the tissue PEG10 transcripts of different size exist. One between 6 and 7 kb, corresponding to the major 6.6 kb PEG10 transcript, as well as minor sized transcripts (Ono et al., 2001; Smallwood et al., 2003; Lux et al., 2005). The major 6.6 kb PEG10 transcript is polyadenylated and at the distal end of exon 2 there are two canonical polyadenylation sequences, AATAAA. In a recent study, minor sized alternatively polyadenylated transcripts were isolated but none of these transcripts contained the typical polyadenylation signal motif at their 3'-end nor any known alternative polyadenylation signal sequence motifs (Lux et al., 2010). If PEG10 transcripts are truly subjected to alternative polyadenylation then future studies have to address the question whether this influences PEG10 expression, mRNA stability, mRNA localisation or translation and if it might be related to pathological processes. Because PEG10 is most likely derived from a retrotransposon it is interesting to note that non-conserved poly(A) sites are associated with transposable elements to a much greater extent than conserved ones (Lee et al., 2008).


  Figure 3. Schematic view of the PEG10-RF1b/2 protein. Shown are the locations of different predicted and proven protein domains.
Description Transcription of PEG10 results in several protein isoforms due to alternative splicing, alternative translation initiation sites, posttranslational proteolytic cleavage and -1 ribosomal frameshift translation. The most prominent feature of PEG10 is its -1 ribosomal frameshift translation mechanism that hints at his retroviral/retrotransposon origin. The existence of PEG10 was reported by three different groups in 2001 (Ono et al., 2001; Shigemoto et al., 2001; Volff et al., 2001). In their search for novelle patternally expressed imprinted genes for an imprinted region on mouse chromosome 6, syntenic to a human imprinting cluster on chromosome 7q21 containing the imprinted SGCE gene, Ono and colleagues performed a database search for EST sequences mapping to this region. Three entries were identified, HB-1 (GenBank Accession No. AF216076), KIAA1051 (GenBank Accession No. AB028974), and 23915 mRNA (GenBank Accession No. AF038197) that were identical and mapped near SGCE. Sequence analysis of these clones predicted two open reading frames with homology to Gag and Pol proteins of some vertebrate retrotransposons, respectively. The deduced gene was named Paternally Expressed Gene 10 (PEG10). Similar results were obtained by Volff and colleagues, when they analysed public sequence databases for long-terminal-repeat (LTR) retrotransposon-like sequences of the Ty3/Gypsy retrotransposon family in mammals. They identified KIAA1051, which showed significant similarities to the Gag structural core protein of some Ty3/Gypsy retrotransposons from the Ty3 family, including Sushi from the pufferfish Fugu rubripes (42.5% similarities), Skippy, Maggy, and Cft1 from different fungi. No significant similarity to other families of Ty3/Gypsy retrotransposons and retroviruses was found and no LTR-like sequences flanking KIAA1051 were identified. It was further reported that the KIAA1051 cDNA contains a partial pol-like sequence (1.5 kb in length), which overlaps the gag-like sequence (1 kb in length) over approximately 250 bp. Its conceptual translation product displayed protease and truncated reverse transcriptase (RT) regions, including well-conserved first and second of the seven RT domains and showed the highest similarity to the Pol protein of again the retrotransposon Sushi (43.7% similarity). Further evidence for the existence of PEG10 came from the work by Shigemoto and colleagues. They analysed the mouse gene Edr, which was identified initially by differential screening of an embryonal carcinoma cDNA library for genes expressed at a reduced level following retinoic acid induced differentiation (Gorman et al., 1985). Their study identified in the Edr gene two open reading frames that overlapped and were set appart by a frameshift of one nucleotide. Subsequent analysis demonstrated that both reading frames are translated by -1 frameshifting (Shigemoto et al., 2001; Lux et al., 2005; Manktelow et al., 2005; Clark et al., 2007).

Translation. In order to perform the -1 frameshift, the reading frame 1 (RF1) - reading frame 2 (RF2) overlap sequence contains a seven nucleotide "slippery" sequence with typical consecutive homopolymeric triplets. The underlined PEG10 "slippery" heptanucleotide sequence G GGA AAC TC follows the general pattern of X XXY YYZ where the A- and P-site tRNAs detach from the zero frame codons XXY YYZ and re-pair after shifting back one nucleotide to XXX YYY and restart translation with the codon after the YYY triplet. Thus, the deduced amino acid sequence of the frameshift site after frameshift translation is GNL. The heptanucleotide "slippery" sequence is completely conserved in all species and the sequence of the downstream pseudoknot is completely conserved in the mammalian species. except for one nucleotide change in the rodent sequence. A detailed analysis of the PEG10 frameshift sequence was done by Manktelow and colleagues (2005).
Due to alternative splicing two transcript variants exist, PEG10-A and PEG10-B, leading to several protein isoforms. These isoforms are first, the result of different translation initiation sites in reading frame 1 (RF1) (Lux et al., 2010). Second, due to the fact, whether the reading frames 1 and 2 (RF2) are translated into an RF1 protein or into an RF1/2 protein by succesfull -1 frameshift translation, and third, in the RF1/2 translation products, shortly after the frameshift site, there is a retroviral typical functional aspartic protease motif usually for Gag-Pol protein processing leading to proteolytic cleavage products (Clark et al., 2007). It was demonstrated that upstream of the originaly predicted ATG translation initiation site (TIS) a second in frame non-ATG exists. For clarification, the non-ATG translation site will be named TIS-1a and the previous ATG start site TIS-2. This non-ATG start codon, a CTG, is 102 nucleotides upstream of the ATG start codon. The alternative splice event that leads to transcript PEG10-B introduces an additional in frame ATG start codon even further upstream of the previous two, which will be named TIS-1b. Their might be an additional TIS further downstream of TIS-2 (Lux et al., 2010). Transcript PEG10-A codes for PEG10-RF1 (using TIS-2), PEG10-RF1a (using TIS-1a), PEG10-RF1/2 and PEG10-RF1a/2. While in theory, transcript PEG10-B can lead to all six isoforms, PEG10-RF1, PEG10-RF1a, PEG10-RF1b (using TIS-1b), PEG10-RF1/2, PEG10-RF1a/2 and PEG10-RF1b/2. Figure 1 shows in a more schematic way the different TIS for transcripts PEG10-A and PEG10-B. The deduced amino acid sequences of the different isoforms are listed in figure 2.
Investigation of PEG10 translation in mouse placenta during gestation and human placenta showed that in vivo both reading frames are translated as an RF1 protein and an RF1/2 fusion protein (Clark et al., 2007). The mouse RF1/2 protein is about 40 kDa larger than the corresponding human protein due to an in frame insertion of approximately 600 nucleotides into the RF2 sequence. Interestingly, the size of RF1 and RF1/2 proteins and the translational frame shift efficiency varies during gestation. From 9.5 dpc when PEG10 expression in mice is first detectable, the 150 kDa frameshift protein is dominant. By using an RF1-specific antibody the frameshift efficiency was estimated and showed an apparent decrease from 68% at 9.5 dpc to 43% by 21.5 dpc. At 15.5 dpc an additional protein of 105 kDa was detected at about equal amounts as the 150 kDa protein. At late gestation, 21.5 dpc, it was present in greater amounts than the 150 kDa PEG10-RF1/2 protein. Mass spectrometry analysis identified the 105 kDa protein as a PEG10 product consisting primarily of PEG10 RF2 but containing peptides from both reading frames. PEG10 protein analysis for amniotic membrane showed a similar profile to that of placenta. Starting with a low expression at 9.5 dpc and then an increased and continued expression throughout gestation. The RF1/2 fusion protein again was the dominant band. Surprisingly, at 10.5 dpc a transient RF1 protein of increased mass of about 50 kDa was detected that disappeared at later time points and only the slightly smaller 47-kDa band identical in size to that in placenta was present again. Furthermore, in this report three RF1 protein populations were detected for HepG2 cells ranging from 47 to 55 kDa. Whether these different PEG10 protein masses are the result of post-translational modifications or due to the use of different TIS or a mixture of both is not clear and awaits further investigations.
In addition, western blot analysis with an RF1-specific antibody of adult mouse heart, spleen and brain tissue extracts showed a weak, single protein band but of different mass, around 50 kDa, for each tissue (Clark et al., 2007). No RF1/2 proteins were detected. The authors concluded based on their further analysis that these proteins do not represent Peg10 proteins.

Protein domains/motifs. By bioinformatic analyses using different programmes like the Simple Modular Architecture Research Tool (SMART), the SUPERFAMILY Sequence Search (SCOP domains) and the Eukaryotic Linear Motif (ELM) resource for functional site prediction, several domains and motifs were predicted. Some are exemplarily shown schematicaly in figure 3 for the 784 amino acid long PEG10-RF1b/2 protein. The Zink-finger domain was consistently identified although the size of the domain varies from amino acid 357-389 or a core region from 370-386 for a ZNF-C2HC (CX2CX4HX4C) consensus sequence, which is highly conserved in Gag proteins in most retroviruses and some retrotransposons. There are two proline rich regions, one at the N-terminus and one at the C-terminus. Proline-rich regions are recognized as presenting binding motifs to, for example, Src homology 2 (SH2) and SH3 domains. The ELM programme predicted the C-terminal proline stretch to be a possible binding site for SH3 domain containing proteins. As already reported, PEG10 contains a retroviral typical aspartyl protease consensus sequence, AMIDSGA. In order to test whether this motif is catalytic active the aspartate was mutated to an alanine (Clark et al., 2007). This change disrupted the protease activity and proved that the aspartyl protease is responsible for the cleavage of the full length PEG10 frameshift protein in to the RF1 and RF2 parts. Taken the protease activity into account the previously estimated PEG10 frameshift efficiency of 15-30% (Shigemoto et al., 2001; Lux et al., 2005) was reestimated to be 60% (Clark et al., 2007).

Interacting proteins. Aside from the protease motif, for none of the other domains it is known whether they are functional nor if they bind to other proteins. The only known binding partners for PEG10 are currently the SIAH1 and SIAH2 proteins (Okabe et al., 2003) and the TGF-beta type I receptor ALK1 (Lux et al., 2005). All three proteins were identified by a yeast two-hybrid screen with the PEG10-RF1 protein and the interactions were confirmed by co-immunoprecipitation experiments. The exact SIAH1/SIAH2 binding region was not determined, but the ELM programme predicted a potential SIAH1 binding site (figure 3, PEG10-RF1b amino acids 329-337). Co-immunoprecipitation experiments by overexpressing PEG10-RF1 and several other type I and II receptors of the TGF-beta superfamily in COS-1 cells showed that PEG10 does also interact with other members of this receptor group (Lux et al., 2005). Nevertheless, when specifically investigated in the two-hybrid assay under stringent conditions none of these receptors reacted with PEG10-RF1 to activate the reporter system. Thus, the most specific interaction appears to be with ALK1.

Expression Based on data obtained from mice, Peg10 is predominantly expressed during embryonic development, whereas later on expression in most tissues ceases or is low except for testis and brain of adult animals (Shigemoto et al., 2001). However, significant induction of Peg10 expression was detected in hepatocellular carcinomas (HCC) and for the regenerating livers of mice after partial hepatectomy (Tsou et al., 2003). Studies with mice by RNA in situ hybridisation showed a high expression during embryonic development especially from day 9.5 to 16.5, specifically in bone and cartilage forming tissues as well as in extra embryonic tissues at all stages between E7.5 and E17.5. For a detailed description see Shigemoto et al. (2001). In humans, expression of PEG10 in adult tissues was seen in brain, kidney, lung, testis and only weak to very weak expression in spleen, liver, colon, small intestine and muscle, but no expression for heart and stomach (Ono et al., 2001). Furthermore, strong expression was also reported for mouse and human placenta. In humans PEG10 expression is low at the early hypoxic phase of placental growth and increases at 11-12 weeks of gestation. This high level of expression is maintained and is significantly increased in term placenta compared with that in early pregnancy (Smallwood et al., 2003). The authors hypothesize that the gene product might be essential for trophoblast differentiation and uterine implantation.
Peg10 expression was observed in relation to adipocyte differentiation in mice. Peg10 was identified as one of the genes expressed early in adipogenesis (Hishida et al., 2007). Expression of Peg10 was elevated after the addition of differentiation inducers in adipocyte differentiable 3T3-L1 cells, but not in the non-adipogenic cell line NIH-3T3. The knockdown of Peg10 by RNA interference inhibited the differentiation of 3T3-L1 cells. Moreover, Peg10 siRNA treatment impaired mitotic clonal expansion (MCE), necessary for adipocyte differentiation, and the crucial expression of C/EBPbeta and C/EBPdelta at the immediate early stage of the differentiation process was inhibited by the knock-down. These results indicate that Peg10 plays an important role at the immediate early stage of adipocyte differentiation.
Aside from bone and cartilage tissue differentiation and adipocyte cell differentiation PEG10 might also be involved in neuronal cell differentiation. In a preliminary experiment with the neuroblastoma cell line SH-SY5Y increasing PEG10 expression was reported over a period of 14 days after treatment with all-trans retinoic acid for differentiation (Lux et al., 2010).
Localisation Data regarding PEG10's cellular localisation do only exist for PEG10-RF1. Okabe and colleagues (2003) report for the hepatoma cell lines HepG2, Huh7 and Alexander as well as for hepatocellular carcinoma (HCC) tissues nuclear and cytoplasmic staining of PEG10 with a PEG10-RF1-specific antibody. In experiments overexpressing PEG10-RF1 in HEK293T cells, only cytoplasmic localisation was reported (Tsou et al., 2003), which was also shown by immunofluorescence analysis with a PEG10-RF1-specific antibody for endogenous PEG10 in HepG2 and B-CLL cells (Lux et al., 2005; Kainz et al., 2007).
Function The knowledge regarding PEG10's protein function is sparse and all direct evidence that exists so far was gained by experiments with the PEG10-RF1 isoform only. No data exists for the recently identified isoform PEG10-RF1a, most likely the major RF1 isoform, or the PEG10-RF1b protein. Functional data regarding the different RF1/2 isoforms are lacking too.
Nevertheless, PEG10-RF1 appears to enhance cell proliferation and blocks apoptosis. Evidence for PEG10's role in cell proliferation were reported by Tsou et al. (2003). Induced PEG10 expression was found during G2/M phase of regenerating mouse liver and elevated expression of PEG10 was found in HCC. The authors state that both, HCC and regenerating mouse livers, represent the two proliferative states of the otherwise quiescent liver tissue. In addition, ectopic expression of PEG10 in 293T cells enhanced cell cycle progression. Complementary data were presented by Okabe and colleagues (2003). The hepatoma cell line, SNU423 that has no endogenous PEG10, was stable transfected with an expression construct for PEG10-RF1 to test the effect of PEG10 on cell growth. The PEG10 stable transfectant cells revealed significant growth promotion compared with the parental or mock cells. Under conditions of serum starvation (0.1% FBS), the mock cells rapidly underwent growth arrest, but stable PEG10-expressing cells continued to proliferate. In the same report, in a yeast two-hybrid screen, the apoptosis inducing protein SIAH1 was identified as a PEG10-RF1 interactor. Overexpression of SIAH1 increased cell death in different hepatoma cell lines, whereas co-expression of PEG10-RF1 in tested SNU423 revealed a partial but significant protection from apoptosis. Anti-apoptotic activity of PEG10 was also reported by Yoshibayashi et al. (2007). The finding that PEG10 enhances cell proliferation was further confirmed by PEG10-specific siRNA knock-down experiments in a series of carcinoma cell lines, i.e. Panc1, HepG2, and Hep3B, which led to a significantly reduced cell proliferation (Li et al., 2006; Yoshibayashi et al., 2007).
Anti-apoptotic activity by PEG10 were not only seen for HCC/hepatoma but also reported for B-cell acute and chronic lymphocytic leukemia, B-ALL and B-CLL. It was observed that B-ALL and B-CLL CD19+CD34+ B cells expressed elevated levels of PEG10, regulated by the chemokines CXCL13 and CCL19 and that these cells were resistant to TNF-alpha induced apoptosis. Treatment of the cells with PEG10 antisense constructs reversed this effect (Hu et al., 2004; Chunsong et al., 2006; Wang et al., 2007). Kainz and colleagues (2007) reported that PEG10 overexpression is associated with high-risk B-CLL. Expression levels in CD19+ B-CLL cells were up to 100-fold higher than in B-cells from healthy donors and expression levels in B-CLL patient samples remained stable over time even after chemotherapy. The intensity of intracellular staining of PEG10 protein corresponded to mRNA levels. Further analysis of PEG10's anti-apoptotic potential showed that short term knock-down (2 days after transfection) of PEG10 in B-CLL cells was not associated with changes in cell survival but long term inhibition (4 days after transfection of PEG10) led to a significant effect on the induction of apoptosis and late apoptosis/necrosis in B-CLL cells.
As described above, during gestation PEG10 is highly expressed in the placenta. Mouse placenta is positive for Peg10 transcripts as well as for proteins from reading frame 1 and reading frame 1/2 (Clark et al., 2007). Peg10 knock-out experiments in mice demonstrated that Peg10 and therefore the Peg10 proteins have an important role during placenta development. Heterozygous knock-outs for the patternal allele died at 10.5 dpc. Their placentas were severely depleted and the labyrinth layer was not developed and the spongiotrophoblast cells were missing (Ono et al., 2006). As discussed by the authors, parthenogenetic embryos die before 9.5 d.p.c. and show early embryonic lethality with poorly developed extraembryonic tissues. Morphological defects of the most developed parthenotes are very similar to those of Peg10-Pat KO embryos; they lack the diploid trophoblast cells of the labyrinth layer and the spongiotrophoblast. However, the majority of parthenotes show more severe phenotypes; suggesting that other genes could also contribute to the parthenogenetic phenotypes. Nevertheless, the result for mouse Peg10 suggests that one of the Peg10 isoforms could be critical for parthenogenetic development in mice and therefore also in man.
Homology PEG10 orthologous sequences can be found in several other eutherian species: Pan troglodytes (chimpanzee), Papio anubis (baboon), Macaca mulatta (Rhesus monkey), Callithrix jacchus (marmoset), Sus scrofa (pig), Canis familiaris (dog), Felis catus (cat), Bos taurus (bovine), Ovis aries (sheep), Mus musculus (mouse), Rattus norvegicus (rat), Rhinolophus ferrumequinum (bat), Sorex araneus (shrew), Monodelphis domestica (opossum) as well as in the metatherian tammar wallaby (Macropus eugenii) (Ono et al., 2001; Brandt et al., 2005a; Brandt et al., 2005b; Suzuki et al., 2007; Clark et al., 2007) and there is a high degree of amino acid conservation. The PEG10 sequence is not conserved in reptiles or birds. Hence, during evolution the PEG10 gene was introduced into the therian mammal genome after the split of birds about 300 million years (myr) ago and after the split of prototherian mammals (monotremes) 166 myr ago, but before the divergence between placental mammals and marsupials about 148 myr ago.

Implicated in

Entity Various cancers
Note Two major pathological conditions are reported in which PEG10 plays a role, hepato cellular carcinomas and B-cell acute and chronic lymphocytic leukemia. As already mentioned above, the presence of PEG10 is linked to resistance of apoptosis and increased cell growth. In addition, further malignancies in which an over expression or prolonged expression of PEG10 was seen are the embryonic kidney malignancy Wilms tumor (Dekel et al., 2006), pancreatic cancer (Li et al., 2006) and the embryonic form of biliary atresia (Zhang et al., 2004).
Widespread DNA copy number alterations are well recognized in HCC and concurrent genomic gains within the chromosome region 7q21 has been implicated in the progression of HCC. In a study by Ip et al. (2007), it was suggested that PEG10 may be a potential biomarker in the progressive development of HCC. Quantitative PCR and qRT-PCR showed the chromosomal gain of 7q21 as well as over expression of PEG10 in HCC cell lines and primary tumors. In addition, qRT-PCR demonstrated a significant progressive trend of increasing PEG10 expression from the putative pre-malignant adjacent livers to early resectable HCC tumors, and to late inoperable HCCs. The authors concluded that genomic gain represents one of the major mechanisms in the induction of PEG10 over expression. This conclusion is further supported by independent data from Tsuji et al. (2010). Increased PEG10 expression might also serve as a biomarker for nephropathy in peripheral blow cells of type 2 diabetes (T2DN) (Guttula et al., 2010).


Transposable elements as a source of genetic innovation: expression and evolution of a family of retrotransposon-derived neogenes in mammals.
Brandt J, Schrauth S, Veith AM, Froschauer A, Haneke T, Schultheis C, Gessler M, Leimeister C, Volff JN.
Gene. 2005a Jan 17;345(1):101-11. Epub 2004 Dec 25.
PMID 15716091
A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes.
Brandt J, Veith AM, Volff JN.
Cytogenet Genome Res. 2005b;110(1-4):307-17.
PMID 16093683
CXC chemokine ligand 13 and CC chemokine ligand 19 cooperatively render resistance to apoptosis in B cell lineage acute and chronic lymphocytic leukemia CD23+CD5+ B cells.
Chunsong H, Yuling H, Li W, Jie X, Gang Z, Qiuping Z, Qingping G, Kejian Z, Li Q, Chang AE, Youxin J, Jinquan T.
J Immunol. 2006 Nov 15;177(10):6713-22.
PMID 17082584
Mammalian gene PEG10 expresses two reading frames by high efficiency -1 frameshifting in embryonic-associated tissues.
Clark MB, Janicke M, Gottesbuhren U, Kleffmann T, Legge M, Poole ES, Tate WP.
J Biol Chem. 2007 Dec 28;282(52):37359-69. Epub 2007 Oct 16.
PMID 17942406
Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney.
Dekel B, Metsuyanim S, Schmidt-Ott KM, Fridman E, Jacob-Hirsch J, Simon A, Pinthus J, Mor Y, Barasch J, Amariglio N, Reisner Y, Kaminski N, Rechavi G.
Cancer Res. 2006 Jun 15;66(12):6040-9.
PMID 16778176
The regulation of gene expression in murine teratocarcinoma cells.
Gorman CM, Lane DP, Watson CJ, Rigby PW.
Cold Spring Harb Symp Quant Biol. 1985;50:701-6.
PMID 3007011
Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy.
Guttula SV, Rao AA, Sridhar GR, Chakravarthy MS, Nageshwararo K, Rao PV.
Int J Diabetes Dev Ctries. 2010 Jan;30(1):52-6.
PMID 20431808
peg10, an imprinted gene, plays a crucial role in adipocyte differentiation.
Hishida T, Naito K, Osada S, Nishizuka M, Imagawa M.
FEBS Lett. 2007 Sep 4;581(22):4272-8. Epub 2007 Aug 10.
PMID 17707377
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.
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.
Cell Mol Immunol. 2004 Aug;1(4):280-94.
PMID 16225771
Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma.
Ip WK, Lai PB, Wong NL, Sy SM, Beheshti B, Squire JA, Wong N.
Cancer Lett. 2007 Jun 8;250(2):284-91. Epub 2006 Nov 28.
PMID 17126992
Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells.
Jie X, Lang C, Jian Q, Chaoqun L, Dehua Y, Yi S, Yanping J, Luokun X, Qiuping Z, Hui W, Feili G, Boquan J, Youxin J, Jinquan T.
Oncogene. 2007 Aug 23;26(39):5741-51. Epub 2007 Mar 19.
PMID 17369855
Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia.
Kainz B, Shehata M, Bilban M, Kienle D, Heintel D, Kromer-Holzinger E, Le T, Krober A, Heller G, Schwarzinger I, Demirtas D, Chott A, Dohner H, Zochbauer-Muller S, Fonatsch C, Zielinski C, Stilgenbauer S, Gaiger A, Wagner O, Jager U.
Int J Cancer. 2007 Nov 1;121(9):1984-93.
PMID 17621626
Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.
Lee JY, Ji Z, Tian B.
Nucleic Acids Res. 2008 Oct;36(17):5581-90. Epub 2008 Aug 30.
PMID 18757892
PEG10 is a c-MYC target gene in cancer cells.
Li CM, Margolin AA, Salas M, Memeo L, Mansukhani M, Hibshoosh H, Szabolcs M, Klinakis A, Tycko B.
Cancer Res. 2006 Jan 15;66(2):665-72.
PMID 16423995
Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1.
Lux A, Beil C, Majety M, Barron S, Gallione CJ, Kuhn HM, Berg JN, Kioschis P, Marchuk DA, Hafner M.
J Biol Chem. 2005 Mar 4;280(9):8482-93. Epub 2004 Dec 16.
PMID 15611116
Genetic and molecular analyses of PEG10 reveal new aspects of genomic organization, transcription and translation.
Lux H, Flammann H, Hafner M, Lux A.
PLoS One. 2010 Jan 13;5(1):e8686.
PMID 20084274
Characterization of the frameshift signal of Edr, a mammalian example of programmed -1 ribosomal frameshifting.
Manktelow E, Shigemoto K, Brierley I.
Nucleic Acids Res. 2005 Mar 14;33(5):1553-63. Print 2005.
PMID 15767280
E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis.
Muller H, Bracken AP, Vernell R, Moroni MC, Christians F, Grassilli E, Prosperini E, Vigo E, Oliner JD, Helin K.
Genes Dev. 2001 Feb 1;15(3):267-85.
PMID 11159908
Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y.
Cancer Res. 2003 Jun 15;63(12):3043-8.
PMID 12810624
A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21.
Ono R, Kobayashi S, Wagatsuma H, Aisaka K, Kohda T, Kaneko-Ishino T, Ishino F.
Genomics. 2001 Apr 15;73(2):232-7.
PMID 11318613
Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality.
Ono R, Nakamura K, Inoue K, Naruse M, Usami T, Wakisaka-Saito N, Hino T, Suzuki-Migishima R, Ogonuki N, Miki H, Kohda T, Ogura A, Yokoyama M, Kaneko-Ishino T, Ishino F.
Nat Genet. 2006 Jan;38(1):101-6. Epub 2005 Dec 11.
PMID 16341224
Identification and characterisation of a developmentally regulated mammalian gene that utilises -1 programmed ribosomal frameshifting.
Shigemoto K, Brennan J, Walls E, Watson CJ, Stott D, Rigby PW, Reith AD.
Nucleic Acids Res. 2001 Oct 1;29(19):4079-88.
PMID 11574691
Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta.
Smallwood A, Papageorghiou A, Nicolaides K, Alley MK, Jim A, Nargund G, Ojha K, Campbell S, Banerjee S.
Biol Reprod. 2003 Jul;69(1):286-93. Epub 2003 Mar 5.
PMID 12620933
Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.
Suzuki S, Ono R, Narita T, Pask AJ, Shaw G, Wang C, Kohda T, Alsop AE, Marshall Graves JA, Kohara Y, Ishino F, Renfree MB, Kaneko-Ishino T.
PLoS Genet. 2007 Apr 13;3(4):e55.
PMID 17432937
Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers.
Tsou AP, Chuang YC, Su JY, Yang CW, Liao YL, Liu WK, Chiu JH, Chou CK.
J Biomed Sci. 2003;10(6 Pt 1):625-35.
PMID 14576465
PEG10 is a probable target for the amplification at 7q21 detected in hepatocellular carcinoma.
Tsuji K, Yasui K, Gen Y, Endo M, Dohi O, Zen K, Mitsuyoshi H, Minami M, Itoh Y, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
Cancer Genet Cytogenet. 2010 Apr 15;198(2):118-25.
PMID 20362226
Ty3/Gypsy retrotransposon fossils in mammalian genomes: did they evolve into new cellular functions?
Volff J, Korting C, Schartl M.
Mol Biol Evol. 2001 Feb;18(2):266-70.
PMID 11158386
PEG10 directly regulated by E2Fs might have a role in the development of hepatocellular carcinoma.
Wang C, Xiao Y, Hu Z, Chen Y, Liu N, Hu G.
FEBS Lett. 2008 Aug 6;582(18):2793-8. Epub 2008 Jul 14.
PMID 18625225
1p31, 7q21 and 18q21 chromosomal aberrations and candidate genes in acquired vinblastine resistance of human cervical carcinoma KB cells.
Wang J, Tai LS, Tzang CH, Fong WF, Guan XY, Yang M.
Oncol Rep. 2008 May;19(5):1155-64.
PMID 18425371
CCL19 and CXCL13 synergistically regulate interaction between B cell acute lymphocytic leukemia CD23+CD5+ B Cells and CD8+ T cells.
Wang X, Yuling H, Yanping J, Xinti T, Yaofang Y, Feng Y, Ruijin X, Li W, Lang C, Jingyi L, Zhiqing T, Jingping O, Bing X, Li Q, Chang AE, Sun Z, Youxin J, Jinquan T.
J Immunol. 2007 Sep 1;179(5):2880-8.
PMID 17709502
SIAH1 causes growth arrest and apoptosis in hepatoma cells through beta-catenin degradation-dependent and -independent mechanisms.
Yoshibayashi H, Okabe H, Satoh S, Hida K, Kawashima K, Hamasu S, Nomura A, Hasegawa S, Ikai I, Sakai Y.
Oncol Rep. 2007 Mar;17(3):549-56.
PMID 17273732
Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia.
Zhang DY, Sabla G, Shivakumar P, Tiao G, Sokol RJ, Mack C, Shneider BL, Aronow B, Bezerra JA.
Hepatology. 2004 Apr;39(4):954-62.
PMID 15057899


This paper should be referenced as such :
Lux, A
PEG10 (paternally expressed 10)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(9):724-730.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)PEG10   14005
LRG (Locus Reference Genomic)LRG_1097
Entrez_Gene (NCBI)PEG10    paternally expressed 10
AliasesEDR; HB-1; MEF3L; Mar2; 
Mart2; RGAG3; RTL2; SIRH1
GeneCards (Weizmann)PEG10
Ensembl hg19 (Hinxton)ENSG00000242265 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000242265 [Gene_View]  ENSG00000242265 [Sequence]  chr7:94656325-94669694 [Contig_View]  PEG10 [Vega]
ICGC DataPortalENSG00000242265
TCGA cBioPortalPEG10
AceView (NCBI)PEG10
Genatlas (Paris)PEG10
SOURCE (Princeton)PEG10
Genetics Home Reference (NIH)PEG10
Genomic and cartography
GoldenPath hg38 (UCSC)PEG10  -     chr7:94656325-94669694 +  7q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PEG10  -     7q21.3   [Description]    (hg19-Feb_2009)
GoldenPathPEG10 - 7q21.3 [CytoView hg19]  PEG10 - 7q21.3 [CytoView hg38]
Genome Data Viewer NCBIPEG10 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB028974 AB049150 AB049834 AF038197 AF216076
RefSeq transcript (Entrez)NM_001040152 NM_001172437 NM_001172438 NM_001184961 NM_001184962 NM_015068
Consensus coding sequences : CCDS (NCBI)PEG10
Gene ExpressionPEG10 [ NCBI-GEO ]   PEG10 [ EBI - ARRAY_EXPRESS ]   PEG10 [ SEEK ]   PEG10 [ MEM ]
Gene Expression Viewer (FireBrowse)PEG10 [ Firebrowse - Broad ]
GenevisibleExpression of PEG10 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23089
GTEX Portal (Tissue expression)PEG10
Human Protein AtlasENSG00000242265-PEG10 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ86TG7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ86TG7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ86TG7
Domaine pattern : Prosite (Expaxy)ZF_CCHC (PS50158)   
Domains : Interpro (EBI)DNA/RNA_pol_sf    DUF4939    LDOC1-rel    Peptidase_aspartic_dom_sf    Rev_trsase/Diguanyl_cyclase    Znf_CCHC    Znf_CCHC_sf   
Domain families : Pfam (Sanger)DUF4939 (PF16297)   
Domain families : Pfam (NCBI)pfam16297   
Conserved Domain (NCBI)PEG10
AlphaFold pdb e-kbQ86TG7   
Human Protein Atlas [tissue]ENSG00000242265-PEG10 [tissue]
Protein Interaction databases
IntAct (EBI)Q86TG7
Ontologies - Pathways
Ontology : AmiGODNA binding  RNA binding  protein binding  nucleoplasm  cytoplasm  cytosol  cytosol  apoptotic process  zinc ion binding  cell differentiation  negative regulation of transforming growth factor beta receptor signaling pathway  
Ontology : EGO-EBIDNA binding  RNA binding  protein binding  nucleoplasm  cytoplasm  cytosol  cytosol  apoptotic process  zinc ion binding  cell differentiation  negative regulation of transforming growth factor beta receptor signaling pathway  
NDEx NetworkPEG10
Atlas of Cancer Signalling NetworkPEG10
Wikipedia pathwaysPEG10
Orthology - Evolution
GeneTree (enSembl)ENSG00000242265
Phylogenetic Trees/Animal Genes : TreeFamPEG10
Homologs : HomoloGenePEG10
Homology/Alignments : Family Browser (UCSC)PEG10
Gene fusions - Rearrangements
Fusion Cancer (Beijing)AD_1 [PEG10]  -  7q21.3 [FUSC000466]
Fusion : QuiverPEG10
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPEG10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PEG10
Exome Variant ServerPEG10
GNOMAD BrowserENSG00000242265
Varsome BrowserPEG10
ACMGPEG10 variants
Genomic Variants (DGV)PEG10 [DGVbeta]
DECIPHERPEG10 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPEG10 
ICGC Data PortalPEG10 
TCGA Data PortalPEG10 
Broad Tumor PortalPEG10
OASIS PortalPEG10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPEG10  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPEG10
Mutations and Diseases : HGMDPEG10
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PEG10
DoCM (Curated mutations)PEG10
CIViC (Clinical Interpretations of Variants in Cancer)PEG10
NCG (London)PEG10
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PEG10
NextProtQ86TG7 [Medical]
Target ValidationPEG10
Huge Navigator PEG10 [HugePedia]
ClinGenPEG10 (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDPEG10
Pharm GKB GenePA33170
Clinical trialPEG10
DataMed IndexPEG10
PubMed88 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:24:55 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us