Alternative titles; symbols
HGNC Approved Gene Symbol: PRDM2
Cytogenetic location: 1p36.21 Genomic coordinates (GRCh38): 1:13,700,188-13,825,079 (from NCBI)
The PR domain is a protein-protein interaction module of about 100 amino acids. PR domain-containing proteins, such as PRDM2, are often involved in transcriptional regulation (Jiang and Huang, 2000).
The RB1 protein (614041) is a target of viral oncoproteins. To explore the hypothesis that viral proteins may be structural mimics of cellular RB-binding proteins that normally mediate RB function, Buyse et al. (1995) searched cDNA libraries for RB-binding proteins. They reported the cloning of a cDNA for the zinc finger protein they called RIZ from rat and human cells. It is a 250-kD nuclear protein containing 8 zinc finger motifs. It contains an RB-binding motif that is related to that of the adenovirus E1A oncoprotein; RIZ also shares an antigenic epitope with the C terminus of E1A. It is expressed in human retinoblastoma cells and at low levels in all other human cell lines examined. While the function of RIZ was not clear, its structure and pattern of expression suggested to Buyse et al. (1995) a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma.
Jiang and Huang (2000) reviewed the PR domain-containing protein family. They stated that the full-length RIZ isoform, RIZ1, is a 1,719-amino acid protein with an N-terminal PR domain, followed by an acidic region, 3 zinc fingers, a central GTPase domain, and a C-terminal region containing a PEST sequence and 5 more zinc fingers. The acidic region and first set of zinc fingers act as the RB-binding domain. The RIZ2 splice variant encodes a protein lacking the N-terminal PR domain.
The RIZ gene contains at least 10 exons and spans more than 150 kb. The majority of the RIZ1 transcript is encoded by exon 7. The RIZ2 splice variant is produced by an internal GC-rich promoter located at the intron-exon boundary of coding exon 5. (Jiang and Huang, 2000).
Using fluorescence in situ hybridization, Buyse et al. (1996) mapped the RIZ gene to 1p36. To further determine the physical location, they screened YACs from the CEPH human megaYAC library and found hybridization to a YAC mapped to 1p36 that had been demonstrated to be nonchimeric. Buyse et al. (1996) commented that RIZ may be a candidate target of 1p36 alterations that commonly occur in neuroendocrine, breast, liver, colon, and lymphoid tumors.
Mock et al. (1996) mapped the Riz gene to mouse chromosome 4.
The distal portion of chromosome 1p is one of the most commonly affected regions in human cancer. In a study of hereditary and sporadic colorectal cancer, Chadwick et al. (2000) identified a region of frequent deletion at 32.2 centimorgans from 1ptel. Deletion breakpoints clustered in the vicinity of or inside the gene RIZ. Sequence analysis demonstrated frequent frameshift mutations of the RIZ gene. The mutations consisted of 1- or 2-bp deletions of coding poly(A) tracts (A)8 or (A)9, and were confined to microsatellite-unstable colorectal tumors, being present in 9 of 24 (37.5%) primary tumors and in 6 of 11 (54.5%) cell lines; in 2 cell lines the mutation was homozygous (or hemizygous). The mutations apparently were selected clonally in tumorigenesis, because similar poly(A) tracts in other genes were not affected. Of the 2 alternative products of the gene, RIZ1 contains a PR domain implicated in tumor suppressor function and RIZ2 lacks this motif. Chadwick et al. (2000) proposed that RIZ is a target of observed 1p alterations, with impairment of the PR domain-mediated function through either frameshift mutation or genomic deletion.
Because alterations in the 1p36 region, where the RIZ gene is located, had been described in malignant melanomas, Poetsch et al. (2002) analyzed the RIZ gene in 16 typical nevi, 19 atypical nevi, 33 primary melanoma lesions and 25 metastases, and DNA from 4 melanoma cell lines. Frameshift mutations were found in 17% of melanoma samples and 8.6% of nevi, but no missense mutations were found in the exons of RIZ. No LOH of the RIZ gene and no microsatellite instability in 6 dinucleotide markers or in the mononucleotide repeats MSH3 (600887) and MSH6 (600678) could be demonstrated in the samples with RIZ frameshift mutations. Although the results did not explain the high rate of deletions in 1p36 in melanoma, Poetsch et al. (2002) concluded that RIZ has a potential role in the multistep tumor-forming process of malignant melanoma of the skin.
Fang et al. (2001) identified a polymorphism in the RIZ gene consisting of the presence or absence of a proline at codon 704 (P704). Grundberg et al. (2004) performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity, P704 +/-) to coactivate the ER-alpha (133430) and examined association of the polymorphism to bone mineral density (BMD; see 601884) in 343 Swedish women, aged 20 to 39 years. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ER-alpha in a ligand- and dose-dependent manner compared with P704+ RIZ (P less than 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704 +/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704 +/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). Grundberg et al. (2004) concluded that RIZ1 may be a candidate gene for involvement in the variation seen in BMD.
Buyse, I. M., Shao, G., Huang, S. The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proc. Nat. Acad. Sci. 92: 4467-4471, 1995. [PubMed: 7538672] [Full Text: https://doi.org/10.1073/pnas.92.10.4467]
Buyse, I. M., Takahashi, E., Huang, S. Physical mapping of the retinoblastoma interacting zinc finger gene RIZ to D1S228 on chromosome 1p36. Genomics 34: 119-121, 1996. [PubMed: 8661032] [Full Text: https://doi.org/10.1006/geno.1996.0249]
Chadwick, R. B., Jiang, G.-L., Bennington, G. A., Yuan, B., Johnson, C. K., Stevens, M. W., Niemann, T. H., Peltomaki, P., Huang, S., de la Chapelle, A. Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. Proc. Nat. Acad. Sci. 97: 2662-2667, 2000. [PubMed: 10688904] [Full Text: https://doi.org/10.1073/pnas.040579497]
Fang, W., Piao, Z., Buyse, I. M., Simon, D., Sheu, J. C., Perucho, M., Huang, S. Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma. Brit. J. Cancer 84: 743-747, 2001. [PubMed: 11259086] [Full Text: https://doi.org/10.1054/bjoc.2000.1667]
Grundberg, E., Carling, T., Brandstrom, H., Huang, S., Ribom, E. L., Ljunggren, O., Mallmin, H., Kindmark, A. A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women. J. Clin. Endocr. Metab. 89: 6173-6178, 2004. [PubMed: 15579774] [Full Text: https://doi.org/10.1210/jc.2004-0403]
Jiang, G.-L., Huang, S. The yin-yang of PR-domain family genes in tumorigenesis. Histol. Histopath. 15: 109-117, 2000. [PubMed: 10668202] [Full Text: https://doi.org/10.14670/HH-15.109]
Mock, B. A., Coleman, M. P., Huang, S. Riz maps to distal chromosome 4 near genes involved in tumorigenesis and nerve degeneration. Mammalian Genome 7: 637 only, 1996. [PubMed: 8679000] [Full Text: https://doi.org/10.1007/s003359900195]
Poetsch, M., Dittberner, T., Woenckhaus, C. Frameshift mutations of RIZ, but no point mutations in RIZ1 exons in malignant melanomas with deletions in 1p36. Oncogene 21: 3038-3042, 2002. [PubMed: 12082534] [Full Text: https://doi.org/10.1038/sj.onc.1205457]