The two isoforms share exon 2 but have different exon 1. The exon 1a of ING2a encodes 58 amino acids. Exon 1b of ING2b encodes 18 amino acids. There is no significant homology between the N-terminal part of ING2b and the N-terminal regions of ING1 isoforms (Unoki et al., 2008).

The promoter region of ING2a possesses two p53 binding sites in contrast to the promoter of ING2b. Binding of p53 to these sites suppresses the ING2a expression. The promoter region of ING2b harbors a HSF1 and HSF2 binding site, a c-Rel, a SP1 and five MZF1 binding sites (Unoki et al., 2008).

ING2 is widely expressed in normal tissues (Shimada et al., 1998).

ING2 is predominantly localized in the nucleus to chromatin and the nuclear matrix (Gozani et al., 2003). Through reduced levels of phosphoinositide PtdIns5P, ING2 might be released from chromatin and translocates partially to the cytoplasm (Gozani et al., 2003).

The tumor suppressor protein ING2 has been described to regulate cell cycle, cellular senescence and gene regulation including chromatin level. In response to DNA damage ING2 enhances the acetylation of p53, which negatively regulates cell proliferation (Nagashima et al., 2001). In addition the level of ING2 expression directly regulates the onset of replicative senescence through the induction of p300-dependent acetylation of p53 (Pedeux et al., 2005). ING2 also induces the global histone H4 acetylation and chromatin relaxation and thereby enhances the nucleotide excision repair (Wang et al., 2006). Furthermore, ING2 is also a part of two related mSin3/HDAC1/HDAC2 corepressor complexes (Doyon et al., 2006). Further, chromatin association of ING2 is linked to ING2 ability to bind to trimethylated K4 of histone 3 (H3K4me3) via its plant homeodomain (PHD) region (Shi et al., 2006). p33ING2 is also associated with histone methyltranferase (HMT-) activity in vitro and in vivo, methylating specifically histone H3 and histone H1 (Goeman et al., 2008). In addition, ING2, as a transcriptional repressor, directly interacts with the corepressor Alien and enhances the Alien-mediated gene silencing (Fegers et al., 2007). Furthermore, ING2 interacts with the Smad-interaction transcriptional modulator SnoN mediating TGF-beta-induced Smad-dependent transcription and cellular responses (Sarker et al., 2008). The activity of ING2, as a nuclear phosphatidylinositol receptor can be modulated by phosphoinositides (Gozani et al., 2003).

The PHD-finger motif is highly-conserved among all ING genes. There are five human ING genes (ING1, ING2, ING3, ING4, ING5) which encode multiple isoforms via splicing. So far known ING2 gene encodes two isoforms (ING2a: 33kDa; ING2b: 28kDA).

So far natural occurring point mutations of ING2 in association with cancer were not yet described. However, loss of heterozygosity (LOH) and aberrant ING2-mRNA levels were associated with cancer.