Spans 150 Kb; 5156 bp coding sequence; 13 exons.

Two promoters localized, respectively, in exon 1 and exon 6 guide the synthesis of two transcripts: the first one encodes for the PR domain-containing product (RIZ1) and the other one for the PR domain-lacking form (RIZ2).

RIZ1(280 kDa) and RIZ2(260 kDa) differ only for the presence in the larger form (RIZ1) of the PR domain. In the sequence of both proteins have been identified several domains:

PR domain (130 aa), endowed with histone-methyltransferase activity (Lys 9 of histone H3) and implicated in protein-protein interactions;

E1A like-domain (100 aa), contains the LXCXE sequence able to interact with the oncosupressor gene Rb;

two zinc-finger clusters;

proline-rich domain, containing a LXXLL motif mediating the interaction with estrogen receptor.

RIZ1 and RIZ2 have an ubiquitous and approximately equimolar expression with higher expression levels in neuroendocrine tissues.

nuclear

RIZ Gene products are endowed with DNA-binding as well as transcription factor-binding activities, as evidenced by the independent isolation of RIZ as a retinoblastoma-binding protein (RIZ), a DNA-binding protein (MTB-Zf), or as a GATA3 transcription factor binding protein (G3B).
MTB-Zf (essentially identical to RIZ2) binds to the MTE DNA element GTCATATGAC of human heme-oxygenase-1 gene and can weakly activate transcription.
G3B (RIZ) interacts with the transcription factor GATA-3, regulating the expression of several genes critical for T-cell function and development.
RIZ proteins bind the estrogen receptor in a hormone-dependent manner, acting as a co-activator.
Estradiol binding to estrogen receptor complex converts RIZ activity from transcriptional repressor into co-activator.
Specific siRNA silencing of RIZ1 form increases the MCF-7 breast cancer cells growth rate.
RIZ proteins act as transcriptional repressors binding to GC-rich or Sp-1-binding elements.

RIZ1 K.O. mice showed a high incidence of diffuse large B-cell lymphomas and a broad spectrum of unusual tumors.

Deletion of the 1p36 region is frequent in several human cancers including neuroblastoma, breast cancer, intestinal tumors, and malignant melanoma.
Frameshift mutations in the two poly adenine tracts, A(8) and A(9), generating truncated RIZ1/2 proteins lacking the COOH-terminal PR-binding motif, were found in MSI-high (MSI-H) primary cancers occurring in the pancreas, stomach, endometrium and colorectum.
The single base substitution that changed A563 in the coding sequence (immediately C-terminal to the PR domain) to a G was found specially in diffuse large B-cell lymphomas (DLBL).
Missense mutation of RIZ1 changing nucleotide G317 to A were discovered in Saos2 human osteosarcoma cells.
RIZ harbors a naturally occurring CCT insertion/deletion polymorphism in exon 8 producing a proline insertion/deletion, modulating the impact of estradiol on bone mineral density (BMD).