DENR (density-regulated protein)

2008-06-01   Line S Reinert , Ronald B Gartenhaus 

University of Maryland Greenebaum Cancer Center, 9-011 BRB, 655 West Baltimore Street, Baltimore, MD 21201, USA

Identity

HGNC
LOCATION
12q24.31
LOCUSID
ALIAS
DRP,DRP1,SMAP-3
FUSION GENES

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 (3UTR) of DENR was found to have a high number of uracyl (U)- and adenine (A)-rich sequences (AREs) (Mazan-Mamczarz and Gartenhaus, 2007).

Proteins

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 3UTR 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 name
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 name
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).

Bibliography

Pubmed IDLast YearTitleAuthors
96285871998drp, a novel protein expressed at high cell density but not during growth arrest.Deyo JE et al
178785262007Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1.Mazan-Mamczarz K et al
104972651999Identification of differentially expressed genes associated with HER-2/neu overexpression in human breast cancer cells.Oh JJ et al
169827402006MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles.Reinert LS et al
17296021992The suil suppressor locus in Saccharomyces cerevisiae encodes a translation factor that functions during tRNA(iMet) recognition of the start codon.Yoon HJ et al

Other Information

Locus ID:

NCBI: 8562
MIM: 604550
HGNC: 2769
Ensembl: ENSG00000139726

Variants:

dbSNP: 8562
ClinVar: 8562
TCGA: ENSG00000139726
COSMIC: DENR

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000139726ENST00000280557O43583
ENSG00000139726ENST00000280557A0A024RBR3
ENSG00000139726ENST00000455982F8VVL1

Expression (GTEx)

0
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30
40
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100

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
287325962017Structural and Functional Insights into Human Re-initiation Complexes.18
287235572017Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1.13
287235572017Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1.13
178785262007Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1.6
298898572018DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation.6
305840922019Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation.4

Citation

Line S Reinert ; Ronald B Gartenhaus

DENR (density-regulated protein)

Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

Online version: http://atlasgeneticsoncology.org/gene/40295/denr