PRDM2 (PR domain containing 2, with ZNF domain)
2008-03-01 Erika Di Zazzo , Bruno Moncharmont AffiliationDipartimento di Scienze per la Salute, Università degli studi del Molise, Via Francesco De Sanctis - edificio polifunzionale III, 86170 Campobasso, Italia
Identity
HGNC
LOCATION
1p36.21
LOCUSID
ALIAS
HUMHOXY1,KMT8,KMT8A,MTB-ZF,RIZ,RIZ1,RIZ2
FUSION GENES
DNA/RNA
Description
Spans 150 Kb; 5156 bp coding sequence; 13 exons.
Transcription
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).
Proteins
Description
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.
Expression
RIZ1 and RIZ2 have an ubiquitous and approximately equimolar expression with higher expression levels in neuroendocrine tissues.
Localisation
nuclear
Function
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.
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.
Mutations
Germinal
RIZ1 K.O. mice showed a high incidence of diffuse large B-cell lymphomas and a broad spectrum of unusual tumors.
Somatic
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).
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).
Implicated in
Entity name
Breast cancer
Disease
The RIZ gene might have a role in human breast cancer. In fact, RIZ1 expression is decreased or lost in human breast cancer, whereas RIZ2 expression is normal.
Entity name
Gastric cancer
Disease
RIZ1 might be a specific target of inactivation in human gastric cancer. Methylation of the RIZ1 promoter was detected in 37% of 30 cases and inactivation of the second allele occurred through frameshift mutation, loss of heterozygosity (LOH) or promoter methylation. Furthermore frameshift mutations in the two coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas.
Entity name
Endometrial carcinoma
Disease
RIZ inactivation is highly selected during the clonal evolution of these tumors. Six (33%) of 18 endometrial carcinomas present frameshift mutation in the two coding polyadenosine tracts of RIZ.
Entity name
Colorectal carcinoma
Disease
RIZ might have a role in human colorectal tumorigenesis. The region 1p36 is frequently deleted in colorectal cancer; Furthermore, 37.5% of microsatellite-unstable colorectal tumors presents frameshift mutation, consisting of 1- or 2-bp deletions of a coding (A)8 or (A)9 tract, of the RIZ gene.
Entity name
Leukaemia
Disease
Suppression of RIZ1 expression or enhancement of RIZ2 expression may have an important role in leukaemogenesis. The expression of RIZ1 was significantly decreased in leukaemia cell lines (14 out of 17, 82%) and in patients with acute myeloblastic leukaemia (8 out of 14, 57%). In contrast, RIZ2 expression was increased in patients with acute lymphoblastic leukaemia (8 out of 11, 73%) compared with normal bone marrow cells.
Entity name
Ovarian carcinoma
Disease
Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of epithelial ovarian carcinoma, and is considered to be caused in part by aberrant DNA methylation. Decreased expression of RIZ1 was significantly correlated with histological subtypes (P < 0.0001), high tumor grade (P = 0.0153), advanced clinical stage (P = 0.0345), and high Ki67 index (P = 0.0117).
Entity name
Neuroblastoma
Disease
Advanced stages of neuroblastoma is genetically characterized by deletions or LOH for the short arm of chromosome 1 suggesting that in the deleted region there is a locus for putative suppressor gene.
Entity name
Hepatoma
Disease
Hepatomas present deletion of the chromosome 1 short arm suggesting that in this region is localized a gene whose functional loss may be involved in hepatocellular carcinogenesis.
Entity name
Prostate cancer
Disease
RIZ1 may be associated with prostate carcinogenesis. Transcriptional inactivation of RIZ1 gene by aberrant DNA methylation of promoter CpG island is detected in 20 (42.6%) of the 47 prostate cancer tissues.
Entity name
Thyroid carcinoma
Disease
RIZ1 have probably an important role in thyroid tumorigenesis. RIZ1 is lost in thyroid tumor cell line and is also significantly reduced in thyroid carcinomas when compared with normal thyroid tissues and benign tumors. The loss of RIZ1 is mediated by aberrant cytosine methylation of the RIZ1 promoter.
Entity name
Lung cancer
Disease
RIZ polymorphisms may be an important predictive markers for lung cancer susceptibility. In fact, the +92337G > A and +95701C > A polymorphisms are associated with reduced risk of lung adenocarcinomas.
Entity name
Ostheoporosis
Disease
The RIZ P704 insertion (+)/deletion (-) polymorphism modulates the impact of estradiol on bone mineral density (BMD). The RIZ P704 +/+ genotype is a risk factor for low BMD in elderly subjects with low estradiol levels, whereas the RIZ P704 +/+ genotype was associated with high BMD in premenopausal women.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10706618 | 2000 | The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action. | Abbondanza C et al |
| 17922684 | 2007 | Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: correlation with epigenetic inactivation by aberrant DNA methylation. | Akahira J et al |
| 8467511 | 1993 | Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis. | Bardi G et al |
| 9223517 | 1997 | In vitro analysis of the E1A-homologous sequences of RIZ. | Buyse IM et al |
| 7538672 | 1995 | The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. | Buyse IM et al |
| 11748455 | 2002 | The tumor suppressor gene RIZ in cancer gene therapy (review). | Canote R et al |
| 15282304 | 2004 | A histone methyltransferase is required for maximal response to female sex hormones. | Carling T et al |
| 10688904 | 2000 | Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. | Chadwick RB et al |
| 2734311 | 1989 | Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. | Dracopoli NC et al |
| 11719434 | 2001 | Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily. | Du Y et al |
| 10862032 | 2000 | Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region. | Fang W et al |
| 1551108 | 1992 | Loss of heterozygosity for chromosomes 1 or 14 defines subsets of advanced neuroblastomas. | Fong CT et al |
| 16356493 | 2006 | Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation. | Gazzerro P et al |
| 2545098 | 1989 | Distal deletion of chromosome Ip in ductal carcinoma of the breast. | Genuardi M et al |
| 17356055 | 2007 | The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism. | Grundberg E et al |
| 17052263 | 2007 | DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer. | Hasegawa Y et al |
| 9766644 | 1998 | RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. | He L et al |
| 10369808 | 1999 | The retinoblastoma protein-interacting zinc finger gene RIZ in 1p36-linked cancers. | Huang S et al |
| 10508492 | 1999 | Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1. | Jiang Gl et al |
| 17103461 | 2006 | RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. | Lal G et al |
| 9006946 | 1997 | The retinoblastoma interacting zinc finger gene RIZ produces a PR domain-lacking product through an internal promoter. | Liu L et al |
| 10544042 | 1999 | Identification of a DNA binding protein cooperating with estrogen receptor as RIZ (retinoblastoma interacting zinc finger protein). | Medici N et al |
| 8654390 | 1996 | cDNA cloning of a novel protein containing two zinc-finger domains that may function as a transcription factor for the human heme-oxygenase-1 gene. | Muraosa Y et al |
| 7712484 | 1995 | Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. | Nagai H et al |
| 10987271 | 2000 | Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. | Piao Z et al |
| 11135439 | 2001 | RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum. | Sakurada K et al |
| 12472571 | 2002 | Altered expression of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukaemia. | Sasaki O et al |
| 1646986 | 1991 | Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. | Simon D et al |
| 7590293 | 1995 | Identification and cloning of the G3B cDNA encoding a 3' segment of a protein binding to GATA-3. | Shapiro VS et al |
| 11544182 | 2001 | Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily. | Steele-Perkins G et al |
| 14534544 | 2003 | Biallelic inactivation of the RIZ1 gene in human gastric cancer. | Tokumaru Y et al |
| 9334209 | 1997 | Transcriptional repression mediated by the PR domain zinc finger gene RIZ. | Xie M et al |
| 17693662 | 2007 | Genetic polymorphisms in the Rb-binding zinc finger gene RIZ and the risk of lung cancer. | Yoon KA et al |
Other Information
Locus ID:
NCBI: 7799
MIM: 601196
HGNC: 9347
Ensembl: ENSG00000116731
Variants:
dbSNP: 7799
ClinVar: 7799
TCGA: ENSG00000116731
COSMIC: PRDM2
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Lysine degradation | KEGG | ko00310 |
| Lysine degradation | KEGG | hsa00310 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36964555 | 2023 | Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation. | 1 |
| 37853459 | 2023 | RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer. | 1 |
| 36964555 | 2023 | Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation. | 1 |
| 37853459 | 2023 | RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer. | 1 |
| 32044406 | 2020 | The absence of PRDM2 involved the tumorigenesis of somatotroph adenomas through regulating c-Myc. | 5 |
| 32044406 | 2020 | The absence of PRDM2 involved the tumorigenesis of somatotroph adenomas through regulating c-Myc. | 5 |
| 29367689 | 2018 | Repression of Akt3 gene transcription by the tumor suppressor RIZ1. | 3 |
| 29367689 | 2018 | Repression of Akt3 gene transcription by the tumor suppressor RIZ1. | 3 |
| 27757741 | 2017 | Methylation Status of the RIZ1 Gene Promoter in Human Glioma Tissues and Cell Lines. | 0 |
| 27830966 | 2017 | A deletion polymorphism in the RIZ gene is associated with increased progression of imatinib treated chronic myeloid leukemia patients. | 2 |
| 28718376 | 2017 | RIZ1 and histone methylation status in pituitary adenomas. | 7 |
| 27757741 | 2017 | Methylation Status of the RIZ1 Gene Promoter in Human Glioma Tissues and Cell Lines. | 0 |
| 27830966 | 2017 | A deletion polymorphism in the RIZ gene is associated with increased progression of imatinib treated chronic myeloid leukemia patients. | 2 |
| 28718376 | 2017 | RIZ1 and histone methylation status in pituitary adenomas. | 7 |
| 25884948 | 2015 | Lower PRDM2 expression is associated with dopamine-agonist resistance and tumor recurrence in prolactinomas. | 11 |
Citation
Erika Di Zazzo ; Bruno Moncharmont
PRDM2 (PR domain containing 2, with ZNF domain)
Atlas Genet Cytogenet Oncol Haematol. 2008-03-01
Online version: http://atlasgeneticsoncology.org/gene/41834/prdm2-(pr-domain-containing-2-with-znf-domain)
