PRDM2 (PR domain containing 2, with ZNF domain)

Identity

Other names	GATA 3 binding protein
	HUMHOXY1
	KMT8
	MTB-ZF(MTE-binding protein zinc-finger)
	RIZ (retinoblastoma interacting zinc-finger protein)
	RIZ1
	RIZ2
HGNC	PRDM2
Location	1p36.21
Location_base_pair	Starts at 13948463 and ends at 13987158 bp from pter (hg18-Mar_2006).

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).

Protein

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.

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).

Implicated in

Entity	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	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	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	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	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	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	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	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	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	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	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	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.

External links

	Nomenclature
HGNC	PRDM2   9347
Entrez_Gene	PRDM2  7799  PR domain containing 2, with ZNF domain
	Cards
Atlas	PRDM2ID41834ch1p36
GeneCards	PRDM2
Ensembl	PRDM2 [Search_View]   ENSG00000116731 [Gene_View]
Genatlas	PRDM2
GeneLynx	PRDM2
eGenome	PRDM2
euGene	7799
	Genomic and cartography
GoldenPath	PRDM2  -  1p36.21   chr1:13948463-13987158 +  1p36   [Description]    (hg18-Mar_2006)
Ensembl	PRDM2 - 1p36 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	PRDM2
	Gene and transcription
Genbank	AB208877 [ ENTREZ ]
Genbank	AK123605 [ ENTREZ ]
Genbank	AK124197 [ ENTREZ ]
Genbank	AK307377 [ ENTREZ ]
Genbank	AK308135 [ ENTREZ ]
RefSeq	NM_001007257 [ SRS ]    NM_001007257 [ ENTREZ ]
RefSeq	NM_012231 [ SRS ]    NM_012231 [ ENTREZ ]
RefSeq	NM_015866 [ SRS ]    NM_015866 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_004873 [ SRS ]    NT_004873 [ ENTREZ ]
RefSeq	NW_001838562 [ SRS ]    NW_001838562 [ ENTREZ ]
RefSeq	NW_925794 [ SRS ]    NW_925794 [ ENTREZ ]
AceView	PRDM2 AceView - NCBI
Unigene	Hs.371823 [ SRS ]    Hs.371823 [ NCBI ]     HS371823 [ spliceNest ]
Fast-db	6715 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q13029 [ SRS]    Q13029 [ EXPASY ]     Q13029 [ INTERPRO ]     Q13029 [ UNIPROT ]
Prosite	PS50280 SET [ SRS ]    PS50280 SET [ Expasy ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR009170 RIZ_retinblas_bd [ SRS ]    IPR009170 RIZ_retinblas_bd [ EBI ]
Interpro	IPR001214 SET [ SRS ]    IPR001214 SET [ EBI ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
CluSTr	Q13029
Pfam	PF00856 SET [ SRS ]    PF00856 SET [ Sanger ]    pfam00856 [ NCBI-CDD ]
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00317 SET [EMBL]
Smart	SM00355 ZnF_C2H2 [EMBL]
Blocks	Q13029
PDB	2JV0 [ SRS ]    2JV0 [ PdbSum ],   2JV0 [ IMB ]   2JV0 [ RSDB ]
PDB	2QPW [ SRS ]    2QPW [ PdbSum ],   2QPW [ IMB ]   2QPW [ RSDB ]
HPRD	03120
	Protein Interaction databases
DIP	Q13029
IntAct	Q13029
	Polymorphism : SNP, mutations, diseases
OMIM	601196    [ map ]
GENECLINICS	601196
SNP	PRDM2 [dbSNP-NCBI]
SNP	NM_001007257 [SNP-NCI]
SNP	NM_012231 [SNP-NCI]
SNP	NM_015866 [SNP-NCI]
SNP	PRDM2 [GeneSNPs - Utah]  PRDM2] [HGBASE - SRS]
HAPMAP	PRDM2 [HAPMAP]
HGMD	PRDM2
	General knowledge
Family Browser	PRDM2 [UCSC Family Browser]
SOURCE	NM_001007257
SOURCE	NM_012231
SOURCE	NM_015866
SMD	Hs.371823
SAGE	Hs.371823
GO	DNA binding [Amigo]  DNA binding
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleus [Amigo]  nucleus
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	zinc ion binding [Amigo]  zinc ion binding
GO	zinc ion binding [Amigo]  zinc ion binding
GO	transcription regulator activity [Amigo]  transcription regulator activity
GO	regulation of transcription [Amigo]  regulation of transcription
GO	metal ion binding [Amigo]  metal ion binding
PubGene	PRDM2
TreeFam	PRDM2
CTD	7799 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PRDM2 Related clones (RZPD - Berlin)
	PubMed
PubMed	34 Pubmed reference(s) in Entrez

Bibliography

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PMID 8467511

The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein.

Buyse IM, Shao G, Huang S.

Proc. Natl. Acad. Sci. U. S. A. 1995 May 9;92(10):4467-71.

PMID 7538672

Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. AUTHORS Nagai H, Negrini M, Carter SL, Gillum DR, Rosenberg AL, Schwartz GF, Croce CM.

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PMID 7712484

Identification and cloning of the G3B cDNA encoding a 3' segment of a protein binding 1:o GATA-3.

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PMID 7590293

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.

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Eur. J. Biochem. 1996 Feb 1;235(3):471-9.

PMID 8654390

In vitro analysis of the E1A-hompologous sequences of RIZ.

Buyse IM, Huang S.

J Virol. 1997 Aug;71(8):6200-3.

PMID 9223517

The retinoblastoma interacting zinc finger gene RIZ produces a PR domain-lacking product through an internal promoter.

Liu L, Shao G, Steele-Perkins G, Huang S.

J Biol Chem. 1997 Jan 31;272(5):2984-91.

PMID 9006946

Transcriptional repression mediated by the PR domain zinc finger gene RIZ.

Xie M, Shao G, Buyse IM, Huang S.

J Biol Chem. 1997 Oct 17;272(42):26360-6.

PMID 9334209

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, Yu JX, Liu L, Buyse IM, Wang MS, Yang QC, Nakagawara A, Brodeur GM, Shi YE, Huang S.

Cancer Res. 1998 Oct 1;58(19):4238-44.

PMID 9766644

The retinoblastoma protein-interacting zinc finger gene RIZ in 1p36-linked cancers.

Huang S.

Font Biosci. 1999 Jun 15;4:D528-32.

PMID 10369808

Decreased RIZ1 expression but not RIZ2 in hepatoma andsuppression of hepatoma tumorigenicity by RIZ1.

Jiang G, Liu L, Buyse IM, Simon D, Huang S.

Int J Cancer 1999 Nov 12;83(4):541-6.

PMID 10508492

Identification of a DNA binding protein cooperating with estrogen receptor as RIZ (retinoblastoma interacting zinc finger protein).

Medici N, Abbondanza C, Nigro V, Rossi V, Piluso G, Belsito A, Gallo L, Roscigno A, Bontempo P, Puca AA, Molinari AM, Moncharmont B, Puca GA.

Biochem Biophys Res Commun. 1999 Nov 2;264(3):983-9.

PMID 10544042

The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action.

Abbondanza C, Medici N, Nigro V, Rossi V, Gallo L, Piluso G, Belsito A, Roscigno A, Bontempo P, Puca AA, Molinari AM, Moncharmont B, Puca GA.

Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3130-5.

PMID 10706618

Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis.

Chadwick RB, Jiang GL, Bennington GA, Yuan B, Johnson CK, Stevens MW, Niemann TH, Peltomaki P, Huang S, de la Chapelle A.

Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2662-7.

PMID 10688904

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, Piao Z, Simon D, Sheu JC, Huang S.

Genes Chromosomes Cancer. 2000 Jul;28(3):269-75.

PMID 10862032

Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability.

Piao Z, Fang W, Malkhosyan S, Kim H, Horii A, Perucho M, Huang S.

Cancer Res. 2000 Sep 1;60(17):4701-4.

PMID 10987271

Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily.

Steele-Perkins G, Fang W, Yang X, Van Gele M, Carling T, Gu J, Buyse IM, Fletcher JA, Liu J, Bronson R, Chadwick RB, de la Chapelle A, Zhang X, Speleman F, Huang S.

Genes Dev. 2001 Sep 1;15(17):2250-62.

PMID 11544182

Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily.

Du Y, Carling T, Fang W, Piao Z, Sheu JC, Huang S.

Cancer Res. 2001 Nov 15;61(22):8094-9.

PMID 11719434

RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum.

Sakurada K, Furukawa T, Kato Y, Kayama T, Huang S, Horii A.

Genes Chromosomes Cancer. 2001 Feb;30(2):207-11.

PMID 11135439

The tumor suppressor gene RIZ in cancer gene therapy.

Canote R, Du Y, Carling T, Tian F, Peng Z, Huang S.

Oncol Rep. 2002 Jan-Feb;9(1):57-60. (REVIEW)

PMID 11748455

Altered expression of retinoblastoma protein-interacting zinc finger gene, RIZ, in human leukaemia.

Sasaki O, Meguro K, Tohmiya Y, Funato T, Shibahara S, Sasaki T.

Br J Haematol. 2002 Dec;119(4):940-8.

PMID 12472571

Biallelic inactivation of the RIZ1 gene in human gastric cancer.

Tokumaru Y, Nomoto S, JerÓnimo C, Henrique R, Harden S, Trink B and Sidransky D.

Oncogene. 2003 Oct 9;22(44):6954-8.

PMID 14534544

A histone methyltransferase is required for maximal response to female sex hormones.

Carling T, Kim KC, Yang XH, Gu J, Zhang XK, Huang S.

Mol Cell Biol. 2004 Aug;24(16):7032-42.

PMID 15282304

Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation.

Gazzerro P, Abbondanza C, D'Arcangelo A, Rossi M, Medici N, Moncharmont B, Puca GA.

Exp Cell Res. 2006 Feb 1;312(3):340-9.

PMID 16356493

RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma.

Lal G, Padmanabha L, Smith BJ, Nicholson RM, Howe JR, O’Dorisio MS, Domann FE Jr.

Cancer. 2006 Dec 15;107(12):2752-9.

PMID 17103461

Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: correlation with epigenetic inactivation by aberrant DNA methylation.

Akahira J, Suzuki F, Suzuki T, Miura I, Kamogawa N, Miki Y, Ito K, Yaegashi N, Sasano H.

Pathol Int. 2007 Nov;57(11):725-33.

PMID 17922684

DNA methylation of the RIZ1 gene is associated with nuclear accumulation of p53 in prostate cancer.

Hasegawa Y, Matsubara A, Teishima J, Seki M, Mita K, Usui T, Oue N, Yasui W.

Cancer Sci. 2007 Jan;98(1):32-6.

PMID 17052263

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, Akesson K, Kindmark A, Gerdhem P, Holmberg A, Mellström D, Ljunggren O, Orwoll E, Mallmin H, Ohlsson C, Brändström H.

J Clin Endocrinol Metab. 2007 Jun;92(6):2300-6.

PMID 17356055

Genetic polymorphisms in the Rb-binding zinc finger gene RIZ and the risk of lung cancer.

Yoon KA, Park S, Hwangbo B, Shin HD, Cheong HS, Shin HR, Lee JS.

Carcinogenesis. 2007 Sep;28(9):1971-7.

PMID 17693662

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Last year publications	automatic search in PubMed

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Contributor(s)

Written	03-2008	Erika Di Zazzo, Bruno Moncharmont
		Dipartimento di Scienze per la Salute, Università degli studi del Molise, Via Francesco De Sanctis - edificio polifunzionale III, 86170 Campobasso, Italia

Citation

This paper should be referenced as such :

Di Zazzo E, Montcharmont B . PRDM2 (PR domain containing 2, with ZNF domain). Atlas Genet Cytogenet Oncol Haematol. March 2008 . URL : http://AtlasGeneticsOncology.org/Genes/PRDM2ID41834ch1p36.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:55:36 2008