DENR (density-regulated protein)
2008-06-01 Line S Reinert  , Ronald B Gartenhaus   AffiliationUniversity 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).
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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9628587 | 1998 | drp, a novel protein expressed at high cell density but not during growth arrest. | Deyo JE et al |
| 17878526 | 2007 | Post-transcriptional control of the MCT-1-associated protein DENR/DRP by RNA-binding protein AUF1. | Mazan-Mamczarz K et al |
| 10497265 | 1999 | Identification of differentially expressed genes associated with HER-2/neu overexpression in human breast cancer cells. | Oh JJ et al |
| 16982740 | 2006 | MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles. | Reinert LS et al |
| 1729602 | 1992 | The 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000139726 | ENST00000280557 | O43583 |
| ENSG00000139726 | ENST00000280557 | A0A024RBR3 |
| ENSG00000139726 | ENST00000455982 | F8VVL1 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38433101 | 2024 | To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes. | 0 |
| 38433101 | 2024 | To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes. | 0 |
| 35115540 | 2022 | Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division. | 16 |
| 35115540 | 2022 | Cyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division. | 16 |
| 32938922 | 2020 | DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4. | 39 |
| 32938922 | 2020 | DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4. | 39 |
| 30584092 | 2019 | Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation. | 13 |
| 30584092 | 2019 | Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation. | 13 |
| 29889857 | 2018 | DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation. | 25 |
| 29889857 | 2018 | DENR-MCTS1 heterodimerization and tRNA recruitment are required for translation reinitiation. | 25 |
| 28723557 | 2017 | Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. | 34 |
| 28723557 | 2017 | Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. | 34 |
| 28732596 | 2017 | Structural and Functional Insights into Human Re-initiation Complexes. | 46 |
| 28723557 | 2017 | Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. | 34 |
| 28723557 | 2017 | Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. | 34 |
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
