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DRAM1 (damage-regulated autophagy modulator)

Written2008-04Michael J Spinella
Department of Pharmacology, Dartmouth Medical School, 7650 Remsen, Hanover NH 03755, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesDNA-damage regulated autophagy modulator 1
Alias_symbol (synonym)FLJ11259
DRAM
Other alias
HGNC (Hugo) DRAM1
LocusID (NCBI) 55332
Atlas_Id 44093
Location 12q23.2  [Link to chromosome band 12q23]
Location_base_pair Starts at 101877327 and ends at 101923623 bp from pter ( according to hg19-Feb_2009)  [Mapping DRAM1.png]
Local_order Cen-SYCP3-GNPTAB-DRAM-LOC100129880-CCDC53-Tel
Fusion genes
(updated 2016)
DRAM1 (12q23.2) / DRAM1 (12q23.2)DRAM1 (12q23.2) / NUP107 (12q15)FRS2 (12q15) / DRAM1 (12q23.2)
KMT2E (7q22.3) / DRAM1 (12q23.2)

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

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

Bibliography

DRAM links autophagy to p53 and programmed cell death.
Crighton D, Wilkinson S, Ryan KM.
Autophagy. 2007 Jan-Feb;3(1):72-4. Epub 2007 Jan 28.
PMID 17102582
 
p53 and metabolism: Inside the TIGAR.
Green DR, Chipuk JE.
Cell. 2006 Jul 14;126(1):30-2.
PMID 16839873
 
The direct p53 target gene, FLJ11259/DRAM, is a member of a novel family of transmembrane proteins.
Kerley-Hamilton JS, Pike AM, Hutchinson JA, Freemantle SJ, Spinella MJ.
Biochim Biophys Acta. 2007 Apr;1769(4):209-19. Epub 2007 Feb 22.
PMID 17397945
 
A global map of p53 transcription-factor binding sites in the human genome.
Wei CL, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T, Shahab A, Yong HC, Fu Y, Weng Z, Liu J, Zhao XD, Chew JL, Lee YL, Kuznetsov VA, Sung WK, Miller LD, Lim B, Liu ET, Yu Q, Ng HH, Ruan Y.
Cell. 2006 Jan 13;124(1):207-19.
PMID 16413492
 
Identification of a new gene (rat TM6P1) encoding a fasting-inducible, integral membrane protein with six transmembrane domains.
Zhang J, D'Ercole AJ, Underwood LE.
Biochim Biophys Acta. 2000 Jun 21;1492(1):280-4.
PMID 10858565
 

Citation

This paper should be referenced as such :
Spinella, MJ
DRAM (damage-regulated autophagy modulator)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(3):194-195.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DRAMID44093ch12q23.html


External links

Nomenclature
HGNC (Hugo)DRAM1   25645
Cards
AtlasDRAMID44093ch12q23
Entrez_Gene (NCBI)DRAM1  55332  DNA damage regulated autophagy modulator 1
AliasesDRAM
GeneCards (Weizmann)DRAM1
Ensembl hg19 (Hinxton)ENSG00000136048 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000136048 [Gene_View]  chr12:101877327-101923623 [Contig_View]  DRAM1 [Vega]
ICGC DataPortalENSG00000136048
TCGA cBioPortalDRAM1
AceView (NCBI)DRAM1
Genatlas (Paris)DRAM1
WikiGenes55332
SOURCE (Princeton)DRAM1
Genetics Home Reference (NIH)DRAM1
Genomic and cartography
GoldenPath hg38 (UCSC)DRAM1  -     chr12:101877327-101923623 +  12q23.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DRAM1  -     12q23.2   [Description]    (hg19-Feb_2009)
EnsemblDRAM1 - 12q23.2 [CytoView hg19]  DRAM1 - 12q23.2 [CytoView hg38]
Mapping of homologs : NCBIDRAM1 [Mapview hg19]  DRAM1 [Mapview hg38]
OMIM610776   
Gene and transcription
Genbank (Entrez)AI079438 AK002121 AK094923 AK297785 BC013773
RefSeq transcript (Entrez)NM_018370
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)DRAM1
Cluster EST : UnigeneHs.525634 [ NCBI ]
CGAP (NCI)Hs.525634
Alternative Splicing GalleryENSG00000136048
Gene ExpressionDRAM1 [ NCBI-GEO ]   DRAM1 [ EBI - ARRAY_EXPRESS ]   DRAM1 [ SEEK ]   DRAM1 [ MEM ]
Gene Expression Viewer (FireBrowse)DRAM1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)55332
GTEX Portal (Tissue expression)DRAM1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N682   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8N682  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8N682
Splice isoforms : SwissVarQ8N682
PhosPhoSitePlusQ8N682
Domains : Interpro (EBI)Frag1/DRAM/Sfk1   
Domain families : Pfam (Sanger)Frag1 (PF10277)   
Domain families : Pfam (NCBI)pfam10277   
Conserved Domain (NCBI)DRAM1
DMDM Disease mutations55332
Blocks (Seattle)DRAM1
SuperfamilyQ8N682
Human Protein AtlasENSG00000136048
Peptide AtlasQ8N682
HPRD07743
IPIIPI00300813   IPI00794266   IPI01021516   IPI01021087   IPI01021226   
Protein Interaction databases
DIP (DOE-UCLA)Q8N682
IntAct (EBI)Q8N682
FunCoupENSG00000136048
BioGRIDDRAM1
STRING (EMBL)DRAM1
ZODIACDRAM1
Ontologies - Pathways
QuickGOQ8N682
Ontology : AmiGOprotein binding  cytoplasm  lysosome  lysosomal membrane  autophagy  apoptotic process  regulation of autophagy  regulation of autophagy  integral component of membrane  
Ontology : EGO-EBIprotein binding  cytoplasm  lysosome  lysosomal membrane  autophagy  apoptotic process  regulation of autophagy  regulation of autophagy  integral component of membrane  
NDEx NetworkDRAM1
Atlas of Cancer Signalling NetworkDRAM1
Wikipedia pathwaysDRAM1
Orthology - Evolution
OrthoDB55332
GeneTree (enSembl)ENSG00000136048
Phylogenetic Trees/Animal Genes : TreeFamDRAM1
HOVERGENQ8N682
HOGENOMQ8N682
Homologs : HomoloGeneDRAM1
Homology/Alignments : Family Browser (UCSC)DRAM1
Gene fusions - Rearrangements
Fusion : MitelmanDRAM1/NUP107 [12q23.2/12q15]  
Fusion : MitelmanFRS2/DRAM1 [12q15/12q23.2]  [t(12;12)(q15;q23)]  
Fusion : MitelmanKMT2E/DRAM1 [7q22.3/12q23.2]  [t(7;12)(q22;q23)]  
Fusion: TCGADRAM1 12q23.2 NUP107 12q15 BLCA
Fusion: TCGAFRS2 12q15 DRAM1 12q23.2 BLCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDRAM1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DRAM1
dbVarDRAM1
ClinVarDRAM1
1000_GenomesDRAM1 
Exome Variant ServerDRAM1
ExAC (Exome Aggregation Consortium)DRAM1 (select the gene name)
Genetic variants : HAPMAP55332
Genomic Variants (DGV)DRAM1 [DGVbeta]
DECIPHERDRAM1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDRAM1 
Mutations
ICGC Data PortalDRAM1 
TCGA Data PortalDRAM1 
Broad Tumor PortalDRAM1
OASIS PortalDRAM1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDRAM1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDRAM1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DRAM1
DgiDB (Drug Gene Interaction Database)DRAM1
DoCM (Curated mutations)DRAM1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DRAM1 (select a term)
intoGenDRAM1
NCG5 (London)DRAM1
Cancer3DDRAM1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610776   
Orphanet
MedgenDRAM1
Genetic Testing Registry DRAM1
NextProtQ8N682 [Medical]
TSGene55332
GENETestsDRAM1
Target ValidationDRAM1
Huge Navigator DRAM1 [HugePedia]
snp3D : Map Gene to Disease55332
BioCentury BCIQDRAM1
ClinGenDRAM1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD55332
Chemical/Pharm GKB GenePA165512564
Clinical trialDRAM1
Miscellaneous
canSAR (ICR)DRAM1 (select the gene name)
Probes
Litterature
PubMed27 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDRAM1
EVEXDRAM1
GoPubMedDRAM1
iHOPDRAM1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jun 30 11:05:12 CEST 2017

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