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RREB1 (Ras Responsive Element Binding Protein 1)

Written2014-02Renty B Franklin, Leslie C Costello
Department of Oncology, Diagnostic Sciences, Dental School, The Greenebaum Cancer Center, University of Maryland, Baltimore, MD, 21201, USA

Abstract Review on RREB1 (Ras Responsive Element Binding Protein 1), with data on DNA, on the protein encoded, and where the gene is implicated.

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HGNC Alias symbHNT
HGNC Alias namehindsight homolog (drosophila)
LocusID (NCBI) 6239
Atlas_Id 51424
Location 6p24.3  [Link to chromosome band 6p24]
Location_base_pair Starts at 7107743 and ends at 7251980 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RREB1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ERBB3 (12q13.2)::RREB1 (6p24.3)FARS2 (6p25.1)::RREB1 (6p24.3)PI4KA (22q11.21)::RREB1 (6p24.3)
RREB1 (6p24.3)::EEF1E1 (6p24.3)RREB1 (6p24.3)::GABARAPL1 (12p13.2)RREB1 (6p24.3)::GPX6 (6p22.1)
RREB1 (6p24.3)::KIFAP3 (1q24.2)RREB1 (6p24.3)::LYRM4 (6p25.1)RREB1 (6p24.3)::PRKDC (8q11.21)
RREB1 (6p24.3)::RREB1 (6p24.3)RREB1 (6p24.3)::TCF12 (15q21.3)RREB1 (6p24.3)::TFE3 (Xp11.23)
RREB1 (6p24.3)::WRN (8p12)RRM2 (2p25.1)::RREB1 (6p24.3)SLCO2A1 (3q22.1)::RREB1 (6p24.3)
SMYD5 (2p13.2)::RREB1 (6p24.3)SNRPN (15q11.2)::RREB1 (6p24.3)


Description The RREB1 gene is 144384 bp. The mRNA is 8568 bp and codes a protein of 1742 amino acids. Nine splice variants of RREB1 are predicted. Variant 1 contains 13 coding exons.
Transcription Five isoforms of RREB1 designated RREB1 alpha, RREB1 beta, RREB1 delta, RREB1 gamma and RREB1 epsilon are expressed through alternative splicing.
Pseudogene None reported.


  Schematic diagram of Homo sapiens RREB1 protein showing clusters of conserved zinc figures (ZnF).
Description RREB1 is a zinc finger nuclear protein of 1742 amino acids that contains 15 zinc fingers of the C2H2 type and belongs to the Krueppel zinc-finger protein family. RREB1 protein-protein interactions include NEUROD1 (Ray et al., 2003) and AR (Mukhopadhyay et al., 2007).
Expression RREB1 is ubiquitously expressed in most tissues; however, it may not be expressed in brain.
Localisation RREB1 expression is localized to nucleus speckle (Date et al., 2004; Fujimoto-Nishiyama et al., 1997).
Function RREB1 binds specifically to the ras-responsive element (RRE) of genes to activate promoter activity and gene transcription. It is involved in regulation of calcitonin expression (Thiagalingam et al., 1996). RREB1 is reported to both activate and repress transcription (Chen et al., 2010). RREB1 reportedly negatively regulates the transcriptional activity of the androgen receptor (Mukhopadhyay et al., 2007). RREB1 is reported to play a role in cell to cell adhesion and regulation of cell movement (Melani et al., 2008). The specific roles of the individual spliced forms are not well defined. RREB1 alpha is not required for proliferation of bladder cancer lines; however, RREB1 beta may be required (Nitz et al., 2011).
Homology With members of the Krueppel family of zinc finger proteins.


Note No disease related mutations are reported.

Implicated in

Entity Colorectal cancer
Note RREB1 is implicated in Ras signaling pathways.
RREB1 is activated through phosphorylation by the MAPK pathway in colorectal cancer (Kent et al., 2013). RREB may play an important role in the development of the primitive gut tube (Lee et al., 2012).
Entity Prostate adenocarcinoma.
Note RREB1 represses the expression of ZIP1 zinc transporter in prostate epithelial cells. Up-regulation of RREB1 in prostate cancer may lead to loss of ZIP1 expression, zinc accumulation and progression of prostate cancer (Milon et al., 2010; Zou et al., 2011).
RREB1 expression in normal and prostate cancer tissue sections.
Entity Pancreatic cancer
Note The zinc level are markedly decreased in pancreatic cancer. The loss of zinc removes its cytotoxic effects on malignant cells. The change in zinc level is associated with decreased expression of the ZIP3 zinc transporter. Recent studies demonstrate that ZIP3 and RREB1 are markedly down regulated with cellular zinc levels. In addition, these changes in zinc, ZIP3 and RREB1 are apparent in PanIn lesions, which are thought to be precancerous lesions leading to ductal adenocarcinoma. Results suggest that down regulation of RREB1 causes down regulation of ZIP3, which results in loss of zinc accumulation in premalignant pancreatic ductal cells (Costello et al., 2012).


Developmental silencing of human zeta-globin gene expression is mediated by the transcriptional repressor RREB1.
Chen RL, Chou YC, Lan YJ, Huang TS, Shen CK.
J Biol Chem. 2010 Apr 2;285(14):10189-97. doi: 10.1074/jbc.M109.049130. Epub 2010 Feb 4.
PMID 20133935
Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma.
Costello LC, Zou J, Desouki MM, Franklin RB.
J Gastrointest Cancer. 2012 Dec;43(4):570-8. doi: 10.1007/s12029-012-9378-1.
PMID 22427155
Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene.
Date S, Nibu Y, Yanai K, Hirata J, Yagami K, Fukamizu A.
Int J Mol Med. 2004 May;13(5):637-42.
PMID 15067362
A novel zinc finger protein, Finb, is a transcriptional activator and localized in nuclear bodies.
Fujimoto-Nishiyama A, Ishii S, Matsuda S, Inoue J, Yamamoto T.
Gene. 1997 Aug 22;195(2):267-75.
PMID 9305772
Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.
Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD, Maitra A, Mendell JT.
Genes Dev. 2010 Dec 15;24(24):2754-9. doi: 10.1101/gad.1950610.
PMID 21159816
Proteomic identification of RREB1, PDE6B, and CD209 up-regulated in primitive gut tube differentiated from human embryonic stem cells.
Lee DH, Ko JJ, Ji YG, Chung HM, Hwang T.
Pancreas. 2012 Jan;41(1):65-73. doi: 10.1097/MPA.0b013e3182223e35.
PMID 21792086
Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.
Melani M, Simpson KJ, Brugge JS, Montell D.
Curr Biol. 2008 Apr 8;18(7):532-7. doi: 10.1016/j.cub.2008.03.024.
PMID 18394891
Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells.
Milon BC, Agyapong A, Bautista R, Costello LC, Franklin RB.
Prostate. 2010 Feb 15;70(3):288-96. doi: 10.1002/pros.21063.
PMID 19802870
The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer.
Mukhopadhyay NK, Cinar B, Mukhopadhyay L, Lutchman M, Ferdinand AS, Kim J, Chung LW, Adam RM, Ray SK, Leiter AB, Richie JP, Liu BC, Freeman MR.
Mol Endocrinol. 2007 Sep;21(9):2056-70. Epub 2007 Jun 5.
PMID 17550981
RREB1 transcription factor splice variants in urologic cancer.
Nitz MD, Harding MA, Smith SC, Thomas S, Theodorescu D.
Am J Pathol. 2011 Jul;179(1):477-86. doi: 10.1016/j.ajpath.2011.03.038.
PMID 21703425
Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector.
Oxford G, Smith SC, Hampton G, Theodorescu D.
Oncogene. 2007 Nov 1;26(50):7143-52. Epub 2007 May 14.
PMID 17496927
Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene promoter by the DNA-binding protein Finb/RREB-1.
Ray SK, Nishitani J, Petry MW, Fessing MY, Leiter AB.
Mol Cell Biol. 2003 Jan;23(1):259-71.
PMID 12482979
RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.
Thiagalingam A, De Bustros A, Borges M, Jasti R, Compton D, Diamond L, Mabry M, Ball DW, Baylin SB, Nelkin BD.
Mol Cell Biol. 1996 Oct;16(10):5335-45.
PMID 8816445
hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).
Zou J, Milon BC, Desouki MM, Costello LC, Franklin RB.
Prostate. 2011 Feb 25. doi: 10.1002/pros.21368.
PMID 21360563


This paper should be referenced as such :
Renty B Franklin, Leslie C Costello
RREB1 (Ras Responsive Element Binding Protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(5):316-318.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)RREB1   10449
Entrez_Gene (NCBI)RREB1    ras responsive element binding protein 1
AliasesFINB; HNT; LZ321; RREB-1; 
GeneCards (Weizmann)RREB1
Ensembl hg19 (Hinxton)ENSG00000124782 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000124782 [Gene_View]  ENSG00000124782 [Sequence]  chr6:7107743-7251980 [Contig_View]  RREB1 [Vega]
ICGC DataPortalENSG00000124782
TCGA cBioPortalRREB1
Genatlas (Paris)RREB1
SOURCE (Princeton)RREB1
Genetics Home Reference (NIH)RREB1
Genomic and cartography
GoldenPath hg38 (UCSC)RREB1  -     chr6:7107743-7251980 +  6p24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RREB1  -     6p24.3   [Description]    (hg19-Feb_2009)
GoldenPathRREB1 - 6p24.3 [CytoView hg19]  RREB1 - 6p24.3 [CytoView hg38]
Genome Data Viewer NCBIRREB1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB019254 AB019351 AB019352 AF072825 AF072826
RefSeq transcript (Entrez)NM_001003698 NM_001003699 NM_001003700 NM_001168344 NM_002955
Consensus coding sequences : CCDS (NCBI)RREB1
Gene ExpressionRREB1 [ NCBI-GEO ]   RREB1 [ EBI - ARRAY_EXPRESS ]   RREB1 [ SEEK ]   RREB1 [ MEM ]
Gene Expression Viewer (FireBrowse)RREB1 [ Firebrowse - Broad ]
GenevisibleExpression of RREB1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6239
GTEX Portal (Tissue expression)RREB1
Human Protein AtlasENSG00000124782-RREB1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)RREB1
Human Protein Atlas [tissue]ENSG00000124782-RREB1 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed73 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:27:17 CEST 2021

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