DRAM (damage-regulated autophagy modulator)

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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DRAM (damage-regulated autophagy modulator)

Identity

Other names	FLJ11259
Location	12q23.2
Location_base_pair	Starts at and ends at bp from pter
Local_order	Cen-SYCP3-GNPTAB-DRAM-LOC100129880-CCDC53-Tel

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)

Protein

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

External links

	Nomenclature
	Cards
SOURCE (Stanford)
	Genomic and cartography
OMIM
	Gene and transcription
Reference sequence (RefSeq transcript) :SRS
Reference transcript : Entrez
RefSeq genomic : SRS
RefSeq genomic : Entrez
	Protein : pattern, domain, 3D structure
Domain families : Pfam SRS
Domain families : Pfam Sanger
Domain families : Pfam NCBI
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
	Protein Interaction databases
	Polymorphism : SNP, mutations, diseases
Hereditary diseases : OMIM
Hereditary diseases : GENETests
	General knowledge
Keywords Ontology : AmiGO
Keywords Ontology : EGO-EBI
Pathways : BIOCARTA
Pathways : KEGG
	Other databases
	Probes
	Literature