DRAM1 (damage-regulated autophagy modulator)

2008-04-01   Michael J Spinella 

Department of Pharmacology, Dartmouth Medical School, 7650 Remsen, Hanover NH 03755, USA

Identity

HGNC
LOCATION
12q23.2
LOCUSID
ALIAS
DRAM
FUSION GENES

DNA/RNA

Description

The gene encompasses 46.3 Kb of DNA and contains 7 exons. All exons are coding with exon 1 and exon 7 containing additional noncoding sequences at their 5 and 3 ends, respectively.

Transcription

The major transcript is 3553 bp. An alternative, in-frame spliced variant has been described that skips exon 4 and exon 5. Significance of this transcript is not known.
DRAM mRNA is induced in a p53-dependent manner after cellular or genotoxic stress. Two alternative functional p53 consensus enhancer elements have been described. DRAM is also induced by p73.
DRAM mRNA appears to be widely expressed in various tissues and cell types. DRAM mRNA is reported to be decreased in various tumor types compared to normal tissue.

Pseudogene

Chromosome 4 (LOC727709)

Proteins

Description

DRAM consists of 238 amino acids. It is predicted to have 6 transmembrane regions. DRAM is a lysosomal protein that is required for induction of autophagy by the p53 pathway.

Expression

No expression data for endogenous DRAM is available at the protein level.

Localisation

Overexpressed and tagged DRAM appears to localize to the lysosome. Localization of endogenous DRAM has not been reported.

Function

The precise function of DRAM is unknown. The first paper reporting a biologic activity for DRAM was in 2006. There is strong evidence from multiple sources that DRAM (FLJ11259) is a direct p53 target gene and is induced in response to DNA damage. This includes global p53-induced gene expression and global p53 ChIP-PET studies. DRAM is a mediator of autophagy and is required for p53-induced apoptosis in response to DNA damage. However, DRAM has minimal effects alone on cell growth or apoptosis. DRAM mRNA is downregulated in some tumors compared to normal. Overall evidence suggests DRAM may be a tumor suppressor downstream of p53. However, whether the role of DRAM in autophagy is positive or negative and whether DRAM mediates cell death or survival in pathologic and physiologic settings may be complex and context dependent.

Homology

DRAM is highly conserved in higher metazoans including C. elegans, Drosophila, and Zebrafish. DRAM shares no homology with any proteins of known function. DRAM has no known functional domains. Human DRAM shares significant homology with other 6 transmembrane proteins of unknown function, including TMEM77, TMEM150 (TM6P1), and FLJ12993. TM6P1 was cloned by subtractive hybridization as induced in starved rat liver. Nutrient starvation is a major physiologic inducer of autophagy.

Mutations

Note

Have not been described.

Implicated in

Entity name
Autophagy
Note
DRAM may be involved in diseases associated with deregulation of autophagy.
DRAM may link p53 and cancer suppression/ treatment to autophagy.

Bibliography

Pubmed IDLast YearTitleAuthors
171025822007DRAM links autophagy to p53 and programmed cell death.Crighton D et al
168398732006p53 and metabolism: Inside the TIGAR.Green DR et al
173979452007The direct p53 target gene, FLJ11259/DRAM, is a member of a novel family of transmembrane proteins.Kerley-Hamilton JS et al
164134922006A global map of p53 transcription-factor binding sites in the human genome.Wei CL et al
108585652000Identification of a new gene (rat TM6P1) encoding a fasting-inducible, integral membrane protein with six transmembrane domains.Zhang J et al

Other Information

Locus ID:

NCBI: 55332
MIM: 610776
HGNC: 25645
Ensembl: ENSG00000136048

Variants:

dbSNP: 55332
ClinVar: 55332
TCGA: ENSG00000136048
COSMIC: DRAM1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000136048ENST00000258534Q8N682
ENSG00000136048ENST00000258534A0A024RBF9
ENSG00000136048ENST00000544152Q8N682
ENSG00000136048ENST00000549066H0YHV0
ENSG00000136048ENST00000549365H0YHJ0
ENSG00000136048ENST00000551403A0A0B4J256

Expression (GTEx)

0
10
20
30
40
50
60

References

Pubmed IDYearTitleCitations
168398812006DRAM, a p53-induced modulator of autophagy, is critical for apoptosis.454
225252722013The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells.89
171025822007DRAM links autophagy to p53 and programmed cell death.75
249225772014The DNA damage-regulated autophagy modulator DRAM1 links mycobacterial recognition via TLR-MYD88 to autophagic defense [corrected].46
233378762013Differential roles of miR-199a-5p in radiation-induced autophagy in breast cancer cells.33
195568852009Analysis of DRAM-related proteins reveals evolutionarily conserved and divergent roles in the control of autophagy.28
236968012013DRAM1 regulates autophagy flux through lysosomes.27
197067542009c-Jun NH2-terminal kinase activation is essential for DRAM-dependent induction of autophagy and apoptosis in 2-methoxyestradiol-treated Ewing sarcoma cells.23
256332932015DRAM1 regulates apoptosis through increasing protein levels and lysosomal localization of BAX.22
213869802011Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway.21

Citation

Michael J Spinella

DRAM1 (damage-regulated autophagy modulator)

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/gene/44093/dram1