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DENR (density-regulated protein)

Identity

Other namesDRP
DRP1
SMAP-3
HGNC (Hugo) DENR
Location 12q24.31
Location_base_pair Starts at 121803324 and ends at 121821906 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description The gene encompasses 18583 bp DNA and contains 8 exons (e.g. NCBI: NC_000012).
Transcription 2766 bp mRNA
The 3'-untranslated region (3'UTR) of DENR was found to have a high number of uracyl (U)- and adenine (A)-rich sequences (AREs) (Mazan-Mamczarz and Gartenhaus, 2007).

Protein

Description Size: 198 amino acids; 22092 Da.
Expression DENR is expressed in variety of tissues, with the highest quantity in skeletal and cardiac muscle. The protein level of DENR is up regulated in parallel with increasing cell density (Deyo et al., 1998). Very recently, it was found that this up regulation is controlled by the AUF-1 protein which binds to the 3'UTR of DENR mRNA and in a cell density-dependent manner (Mazan-Mamczarz and Gartenhaus, 2007). Furthermore, Oh JJ. et al. showed that DENR expression is increased in association with HER-2 overexpression in ovarian and breast cancers (Oh et al., 1999).
Localisation Predominantly in the cytoplasm of 3T3 cells.
Function Until recently there was little published data regarding DENR function. Reinert et al. showed that the oncogene MCT-1 interacts with DENR in vivo and in vitro. DENR contains a SUI1 domain which is also found in translation initiation factor eIF1, where the SUI1 domain is involved in recognition of the translation initiation codon (Yoon and Donahue, 1992). Interestingly, DENR together with MCT-1 sediment in the translation initiation complex fraction in both human embryonic kidney cell cultures and lymphoid cell lines. This complex was shown to interact with the cap complex and to alter the mRNA translational profile of a subset of cancer-related mRNAs. This supports a model where MCT-1 exerts it ongogenic function, at least in part by recruiting the SUI1 domain containing DENR to the translation initiation complex, thereby modulating the translational profile (Reinert et al., 2006).
Homology The SUI1 domain present in DENR is homologous to the SUI-1 domain found in eIF1. The SUI1 domain contains a secondary structure fold corresponding to that found in a number of ribosomal proteins and RNA-binding domains.

Implicated in

Entity Lymphoma oncogene
Note The MCT-1 oncogene protein modifies mRNA translational profiles through its interaction with DENR which contains an SUI1 domain involved in recognition of the translation initiation codon (Reinert et.al., 2006) (Yoon and Donahue, 1992).
  
Entity Ovarian cancer and Breast cancer
Disease DENR expression is increased in association with HER-2 overexpression in ovarian and breast cancers (Oh. et al., 1999).
  

External links

Nomenclature
HGNC (Hugo)DENR   2769
Entrez_Gene (NCBI)DENR  8562  density-regulated protein
Cards
AtlasDENRID40295ch12q24
GeneCards (Weizmann)DENR
Ensembl (Hinxton)ENSG00000139726 [Gene_View]  DENR [Vega]
AceView (NCBI)DENR
Genatlas (Paris)DENR
euGene (Indiana)8562
SOURCE (Stanford)NM_003677
Gene Expression (Array Express) ENSG00000139726
Genomic and cartography
GoldenPath (UCSC)DENR  -  12q24.31   chr12:121803324-121821906 +  12q24.31   [Description]    (hg18-Mar_2006)
EnsemblDENR - 12q24.31 [CytoView]
Mapping of homologs : NCBIDENR [Mapview]
OMIM604550   
Gene and transcription
Gene : Genbank (Entrez)AB014731 AF038554 AF103800 AI093093 AK299463
Reference sequence (RefSeq transcript) :SRSNM_003677
Reference transcript : EntrezNM_003677
RefSeq genomic : SRSAC_000055 AC_000144 NC_000012 NT_009755 NW_001838064 NW_925395
RefSeq genomic : EntrezAC_000055 AC_000144 NC_000012 NT_009755 NW_001838064 NW_925395
Consensus coding sequences : CCDS NCBIDENR
Cluster EST : UnigeneHs.22393 [ SRS ] Hs.22393 [ NCBI ]
Alternative Splicing : Fast-db (Paris)14548
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO43583 (SRS) O43583 (Expasy) O43583 (Uniprot)
With graphics : InterProO43583
Splice isoforms : VarSplice FASTAO43583(VarSplice FASTA)
Domaine pattern : Prosite (SRS)SUI1 (PS50296)   
Domain pattern : Prosite (Expaxy)SUI1 (PS50296)   
Domains : Interpro (SRS)Drp1    TIF_SUI1   
Domains : Interpro (EBI)Drp1    TIF_SUI1   
Related proteins : CluSTrO43583
Domain families : Pfam SRSSUI1 (PF01253)   
Domain families : Pfam SangerSUI1 (PF01253)   
Domain families : Pfam NCBIpfam01253   
Blocks (Seattle)O43583
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD05182
Protein Interaction databases
DIP (DOE-UCLA)O43583
IntAct (EBI)O43583
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIDENR
SNP : GeneSNP UtahDENR
SNP : HGBaseDENR
Genetic variants : HAPMAPDENR
Mutations and Diseases : HGMDDENR
Hereditary diseases : OMIM604550   
Hereditary diseases : GENETests604550   
Diseases : Genetic AssociationDENR
General knowledge
Homologs : HomoloGeneDENR
Homology/Alignments : Family Browser UCSCDENR
Phylogenetic Trees/Animal Genes : TreeFamDENR
Chemical/Protein Interactions : CTD8562
Keywords Ontology : AmiGOmolecular_function  translation initiation factor activity  cellular_component  translational initiation  biological_process  
Keywords Ontology : EGO-EBImolecular_function  translation initiation factor activity  cellular_component  translational initiation  biological_process  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesDENR Related clones (RZPD - Berlin)
Literature
PubMed7 Pubmed reference(s) in Entrez
PubGeneDENR

Bibliography

The suil suppressor locus in Saccharomyces cerevisiae encodes a translation factor that functions during tRNA(iMet) recognition of the start codon.
Yoon HJ, Donahue TF.
Mol Cell Biol. 1992 Jan;12(1):248-60.
PMID 1729602
 
drp, a novel protein expressed at high cell density but not during growth arrest.
Deyo JE, Chiao PJ, Tainsky MA.
DNA Cell Biol. 1998 May;17(5):437-47.
PMID 9628587
 
Identification of differentially expressed genes associated with HER-2/neu overexpression in human breast cancer cells.
Oh JJ, Grosshans DR, Wong SG, Slamon DJ.
Nucleic Acids Res. 1999 Oct 15;27(20):4008-17.
PMID 10497265
 
MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles.
Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M, Bachman KE, He H, Gartenhaus RB.
Cancer Res. 2006 Sep 15;66(18):8994-9001.
PMID 16982740
 
Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1.
Mazan-Mamczarz K, Gartenhaus RB.
Cancer Genomics Proteomics. 2007 May-Jun;4(3):233-9.
PMID 17878526
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written06-2008Line S Reinert, Ronald B Gartenhaus
University of Maryland Greenebaum Cancer Center, 9-011 BRB, 655 West Baltimore Street, Baltimore, MD 21201, USA

Citation

This paper should be referenced as such :
Reinert LS, Gartenhaus RB . DENR (density-regulated protein). Atlas Genet Cytogenet Oncol Haematol. June 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/DENRID40295ch12q24.html

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indexed on : Sat Feb 27 10:47:17 CET 2010

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