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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.

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)HNT
Other aliasFINB
LZ321
RREB-1
Zep-1
HGNC (Hugo) RREB1
LocusID (NCBI) 6239
Atlas_Id 51424
Location 6p24.3  [Link to chromosome band 6p24]
Location_base_pair Starts at 7107853 and ends at 7251980 bp from pter ( according to hg19-Feb_2009)  [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)

DNA/RNA

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.

Protein

 
  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.

Mutations

Note No disease related mutations are reported.

Implicated in

Note
  
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).
  

Bibliography

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
 

Citation

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 ]
On line version : http://AtlasGeneticsOncology.org/Genes/RREB1ID51424ch6p24.html


External links

Nomenclature
HGNC (Hugo)RREB1   10449
Cards
AtlasRREB1ID51424ch6p24
Entrez_Gene (NCBI)RREB1  6239  ras responsive element binding protein 1
AliasesFINB; HNT; LZ321; RREB-1; 
Zep-1
GeneCards (Weizmann)RREB1
Ensembl hg19 (Hinxton)ENSG00000124782 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000124782 [Gene_View]  chr6:7107853-7251980 [Contig_View]  RREB1 [Vega]
ICGC DataPortalENSG00000124782
TCGA cBioPortalRREB1
AceView (NCBI)RREB1
Genatlas (Paris)RREB1
WikiGenes6239
SOURCE (Princeton)RREB1
Genetics Home Reference (NIH)RREB1
Genomic and cartography
GoldenPath hg38 (UCSC)RREB1  -     chr6:7107853-7251980 +  6p24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RREB1  -     6p24.3   [Description]    (hg19-Feb_2009)
EnsemblRREB1 - 6p24.3 [CytoView hg19]  RREB1 - 6p24.3 [CytoView hg38]
Mapping of homologs : NCBIRREB1 [Mapview hg19]  RREB1 [Mapview hg38]
OMIM602209   
Gene and transcription
Genbank (Entrez)AB019254 AB019351 AB019352 AF072825 AF072826
RefSeq transcript (Entrez)NM_001003698 NM_001003699 NM_001003700 NM_001168344 NM_002955
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RREB1
Cluster EST : UnigeneHs.298248 [ NCBI ]
CGAP (NCI)Hs.298248
Alternative Splicing GalleryENSG00000124782
Gene ExpressionRREB1 [ NCBI-GEO ]   RREB1 [ EBI - ARRAY_EXPRESS ]   RREB1 [ SEEK ]   RREB1 [ MEM ]
Gene Expression Viewer (FireBrowse)RREB1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression 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
UniProt/SwissProtQ92766   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ92766  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ92766
Splice isoforms : SwissVarQ92766
PhosPhoSitePlusQ92766
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
Domain families : Pfam (Sanger)zf-C2H2_6 (PF13912)   
Domain families : Pfam (NCBI)pfam13912   
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)RREB1
DMDM Disease mutations6239
Blocks (Seattle)RREB1
SuperfamilyQ92766
Human Protein Atlas [tissue]ENSG00000124782-RREB1 [tissue]
Peptide AtlasQ92766
HPRD03733
IPIIPI00465287   IPI00465288   IPI00853504   IPI00853192   IPI00946914   IPI00947453   IPI00947099   IPI00946916   IPI00947293   
Prote)n InTer`ction databases
DIP (DOE-UCLA)Q92766
IntAct (EBI)Q92766
FunCoupENSG00000124782
BioGRIDRREB1
STRING (EMBL)RREB1
ZODIACRREB1
Ontologies - Pathways
QuickGOQ92766
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding  fibrillar center  transcription factor activity, sequence-specific DNA binding  nucleus  cytoplasm  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  Ras protein signal transduction  multicellular organism development  positive regulation of epithelial cell migration  nuclear body  nuclear speck  positive regulation of mammary gland epithelial cell proliferation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  extracellular exosome  positive regulation of substrate adhesion-dependent cell spreading  positive regulation of wound healing, spreading of epidermal cells  positive regulation of lamellipodium morphogenesis  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding  fibrillar center  transcription factor activity, sequence-specific DNA binding  nucleus  cytoplasm  regulation of transcription, DNA-templated  transcription from RNA polymerase II promoter  Ras protein signal transduction  multicellular organism development  positive regulation of epithelial cell migration  nuclear body  nuclear speck  positive regulation of mammary gland epithelial cell proliferation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  extracellular exosome  positive regulation of substrate adhesion-dependent cell spreading  positive regulation of wound healing, spreading of epidermal cells  positive regulation of lamellipodium morphogenesis  
NDEx NetworkRREB1
Atlas of Cancer Signalling NetworkRREB1
Wikipedia pathwaysRREB1
Orthology - Evolution
OrthoDB6239
GeneTree (enSembl)ENSG00000124782
Phylogenetic Trees/Animal Genes : TreeFamRREB1
HOVERGENQ92766
HOGENOMQ92766
Homologs : HomoloGeneRREB1
Homology/Alignments : Family Browser (UCSC)RREB1
Gene fusions - Rearrangements
Fusion : MitelmanFARS2/RREB1 [6p25.1/6p24.3]  [t(6;6)(p24;p25)]  
Fusion : MitelmanPI4KA/RREB1 [22q11.21/6p24.3]  [t(6;22)(p24;q11)]  
Fusion : MitelmanRREB1/EEF1E1 [6p24.3/6p24.3]  [t(6;6)(p24;p24)]  
Fusion : MitelmanRREB1/GABARAPL1 [6p24.3/12p13.2]  [t(6;12)(p24;p13)]  
Fusion : MitelmanRREB1/GPX6 [6p24.3/6p22.1]  [t(6;6)(p22;p24)]  
Fusion : MitelmanRREB1/LYRM4 [6p24.3/6p25.1]  [t(6;6)(p24;p25)]  
Fusion : MitelmanRREB1/TFE3 [6p24.3/Xp11.23]  [t(X;6)(p11;p24)]  
Fusion : MitelmanRRM2/RREB1 [2p25.1/6p24.3]  [t(2;6)(p25;p24)]  
Fusion: TCGAFARS2 6p25.1 RREB1 6p24.3 BRCA
Fusion: TCGAPI4KA 22q11.21 RREB1 6p24.3 LUSC
Fusion: TCGARREB1 6p24.3 EEF1E1 6p24.3 GBM
Fusion: TCGARREB1 6p24.3 GABARAPL1 12p13.2 PRAD
Fusion: TCGARREB1 6p24.3 GPX6 6p22.1 BRCA
Fusion: TCGARREB1 6p24.3 LYRM4 6p25.1 LGG
Fusion: TCGARRM2 2p25.1 RREB1 6p24.3 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRREB1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RREB1
dbVarRREB1
ClinVarRREB1
1000_GenomesRREB1 
Exome Variant ServerRREB1
ExAC (Exome Aggregation Consortium)ENSG00000124782
GNOMAD BrowserENSG00000124782
Genetic variants : HAPMAP6239
Genomic Variants (DGV)RREB1 [DGVbeta]
DECIPHERRREB1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRREB1 
Mutations
ICGC Data PortalRREB1 
TCGA Data PortalRREB1 
Broad Tumor PortalRREB1
OASIS PortalRREB1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRREB1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRREB1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RREB1
DgiDB (Drug Gene Interaction Database)RREB1
DoCM (Curated mutations)RREB1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RREB1 (select a term)
intoGenRREB1
NCG5 (London)RREB1
Cancer3DRREB1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602209   
Orphanet126   
MedgenRREB1
Genetic Testing Registry RREB1
NextProtQ92766 [Medical]
TSGene6239
GENETestsRREB1
TarGet VqlédationRREB1
Huge Navigator RREB1 [HugePedia]
snp3D : Map Gene to Disease6239
BioCentury BCIQRREB1
ClinGenRREB1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6239
Chemical/Pharm GKB GenePA34864
Clinical trialRREB1
Miscellaneous
canSAR (ICR)RREB1 (select the gene name)
Probes
Litterature
PubMed50 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRREB1
EVEXRREB1
GoPubMedRREB1
iHOPRREB1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:32:50 CEST 2017

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