PEG10

This is a paternally expressed imprinted gene that is thought to have been derived from the Ty3/Gypsy family of retrotransposons. It contains two overlapping open reading frames, RF1 and RF2, and expresses two proteins: a shorter, gag-like protein (with a CCHC-type zinc finger domain) from RF1; and a longer, gag/pol-like fusion protein (with an additional aspartic protease motif) from RF1/RF2 by -1 translational frameshifting (-1 FS). While -1 FS has been observed in RNA viruses and transposons in both prokaryotes and eukaryotes, this gene represents the first example of -1 FS in a eukaryotic cellular gene. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC) and pseudoknot elements required for -1 FS. It is expressed in adult and embryonic tissues (most notably in placenta) and reported to have 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. Additional isoforms resulting from alternatively spliced transcript variants, and use of upstream non-AUG (CUG) start codon have been reported for this gene. [provided by RefSeq, Oct 2014]

Full Name

Paternally Expressed 10

Function

Retrotransposon-derived protein that binds its own mRNA and self-assembles into virion-like capsids (PubMed:34413232).
Forms virion-like extracellular vesicles that encapsulate their own mRNA and are released from cells, enabling intercellular transfer of PEG10 mRNA (PubMed:34413232).
Binds its own mRNA in the 5'-UTR region, in the region near the boundary between the nucleocapsid (NC) and protease (PRO) coding sequences and in the beginning of the 3'-UTR region (PubMed:34413232).
Involved in placenta formation: required for trophoblast stem cells differentiation (By similarity).
Involved at the immediate early stage of adipocyte differentiation (By similarity).
Overexpressed in many cancers and enhances tumor progression: promotes cell proliferation by driving cell cycle progression from G0/G1 (PubMed:12810624, PubMed:16423995, PubMed:26235627, PubMed:28193232).
Enhances cancer progression by inhibiting the TGF-beta signaling, possibly via interaction with the TGF-beta receptor ACVRL1 (PubMed:15611116, PubMed:26235627, PubMed:30094509).
May bind to the 5'-GCCTGTCTTT-3' DNA sequence of the MB1 domain in the myelin basic protein (MBP) promoter; additional evidences are however required to confirm this result (By similarity).

Biological Process

Apoptotic processIEA:UniProtKB-KW
Cell differentiationIEA:UniProtKB-KW
mRNA transportISS:UniProtKB
Negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:HGNC-UCL
Protein homooligomerizationISS:UniProtKB
Vesicle-mediated intercellular transportISS:UniProtKB

Cellular Location

Extracellular vesicle membrane
Cytoplasm
Nucleus
Forms virion-like extracellular vesicles that are released from cells (PubMed:34413232).
Detected predominantly in the cytoplasm of breast and prostate carcinomas, in hepatocellular carcinoma (HCC) and B-cell chronic lymphocytic leukemia (B-CLL) cells and in the Hep-G2 cell line (PubMed:12810624).

PTM

Isoform 1
Undergoes proteolytic cleavage.