The PA2G4 gene contains 13 exons. The sizes of the exons 1-13 are 88, 128, 105, 69, 92, 63, 78, 78, 133, 94, 127, 53 and 65 bp (to the stop codon). Exon 1 contains the translation initiation ATG. Exon 13 contains the stop codon.

The human PA2G4 promoter contains several putative transcription factor binding sites. The major transcript length is 2643 nt. Two proteins are translated due to alternative splicing (Liu et al., 2006). An alternatively spliced version missing 29 NT between the first and third ATGs has been observed.
The PA2G4 promoter contains two tandem DNA elements that bind E2F1. E2F1 increases endogenous EBP1 mRNA levels in cancer cells, but decreases EBP1 mRNA abundance in non transformed cells (Judah et al., 2010).

Six pseudogenes, located on chromosomes 3, 6, 9, 18, 20 and X, have been identified.

p38-2G4 was initially isolated as a DNA binding protein from mouse Ehrlich ascites cells (Radomski and Jost, 1995). The MW of this protein is predicted to be 38058 D, consisting of 340 amino acids. The human orthologue EBP1 was later identified as an ErbB3 binding protein of the same MW as the mouse protein (Yoo et al., 2000). This form migrates at approximately 42 kD in SDS-PAGE gels. Later, a larger 394 amino acid form (predicted MW 43787 D, migrating at 48 kD) was observed in mammalian cells (Xia et al., 2001). The two forms have been demonstrated to be the result of alternative splicing (Liu et al., 2006) or usage of alternative translation initiation sites (Xia et al., 2001). Amino acids 1-48 are required for nucleolar localization and the C terminal domain (aa 364-394) is required for interactions with nucleic acids (Moonie et al., 2007) and protein (Zhang et al., 2002).
EBP1 is post translationally modified at several phosphorylation sites (Ser 360 (Ahn et al., 2006), Ser 363 (Akinmade et al., 2007) and Thr 261 (Akinmade et al., 2008)) in vivo. The protein stability of the short form is regulated by ubiquitination (Liu et al., 2009). The short form is also sumoylated by the TLF/FUS E3 ligase and this sumoylation is required for the anti-proliferative effects of EBP1 (Oh et al., 2010).
The crystal structure of both murine (Monie et al., 2007) and human (Kowalinski et al., 2007) EBP1 has been solved. There is a core domain that is homologous to methionine aminopeptidases, although no enzymatic activity has been reported. The C terminal domain containing a Lys-rich nuclear hormone receptor binding motif (LKALL) was reported to mediate RNA binding (Monie et al., 2007).

EBP1 has been found to be ubiquitously expressed with high expression levels in skeletal muscle (Yoo et al., 2000).

Under logarithmically growing conditions in cell culture, EBP1 localizes to the nucleolus and the cytoplasm (Xia et al., 2001; Squatrito et al., 2004). Upon stimulation with the ErbB3 ligand heregulin, the short form of EBP1 is recruited to the nucleus in AU565 breast cancer cells (Yoo et al., 2000). Sumoylation is required for nuclear translocation (Oh et al., 2010). In primary normal epithelial cells, EBP1 is confined to the cytoplasm (Zhang et al., 2008b).

EBP1 was initially isolated as a cell cycle-regulated DNA binding protein (Radomski and Jost, 1995) and has been shown to induce cell cycle arrest in the G2/M phase of the cell cycle (Zhang et al., 2005). EBP1 acts as a corepressor for several proliferation-associated genes including Cyclin D1, E2F1 (Zhang and Hamburger, 2004) and the androgen receptor (Zhang et al., 2005). EBP1 inhibits transcription of these genes by recruiting HDAC2 via Sin3A to the E2F1 and AR-regulated promoters (Zhang et al., 2005). EBP1 interacts with RB1 and the interaction is enhanced upon EBP1 dephosphorylation (Xia et al., 2001).
EBP1 was isolated as an ErbB3 binding protein using a yeast-two hybrid screen (Yoo et al., 2000). The interactions of EBP1 with ErbB3 is disrupted by the ErbB3 ligand heregulin, leading to EBP1 nuclear translocation. This leads to the eventual inhibition of heregulin-stimulated proliferation, presumably due to the repression of proliferation associated genes (Zhang et al., 2008a).
EBP1 also binds RNA and associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. It has been implicated in the regulation of intermediate and late steps of rRNA processing (Squatrito et al., 2004; Squatrito et al., 2006). EBP1 also mediates cap-independent translation of specific viral IRES (internal ribosome entry site) (Pilipenko et al., 2000). EBP1 regulates translation of AR mRNA (Zhou et al., 2010).
EBP1 has also been implicated in protein stability via its interaction with the proteasome. Overexpression of EBP1 results in decreased stability of ErbB2 protein in breast cancer cells via a proteasome-mediated pathway (Lu et al., 2011). The long form of EBP1 binds to the p53 E3 ligase HDM2, enhancing HDM2-p53 interactions and promoting p53 degradation (Kim et al., 2011).
The long (p48) and short (p42) forms of EBP1 have opposing biological effects, with the longer form inducing cell survival and the shorter form inhibiting cell growth (Liu et al., 2006). The long form binds HDM2, promoting degradation of p53 (Kim et al., 2010).

Similar (30% identity) to the 42 kDA DNA binding protein SF00553 in S. pombe yeast (Yamada et al., 1994) and StEBP1 in potato (Horvath et al., 2006). The orthologue in potatoes (StEBP1) has 69% sequence similarity to human EBP1 and can inhibit growth of human breast cancer cell lines and E2F1 expression in these cells.

No mutations in the PA2G4 gene have been reported.

None reported.