General Information of Drug Off-Target (DOT) (ID: OTBOCZH8)

DOT Name DNA damage-regulated autophagy modulator protein 2 (DRAM2)
Synonyms Transmembrane protein 77
Gene Name DRAM2
Related Disease
Classic Hodgkin lymphoma ( )
Cone-rod dystrophy 2 ( )
Cone-rod dystrophy 21 ( )
Inherited retinal dystrophy ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Polycystic ovarian syndrome ( )
Promyelocytic leukaemia ( )
Retinoblastoma ( )
Tuberculosis ( )
Retinopathy ( )
Cone-rod dystrophy ( )
UniProt ID
DRAM2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF10277
Sequence
MWWFQQGLSFLPSALVIWTSAAFIFSYITAVTLHHIDPALPYISDTGTVAPEKCLFGAML
NIAAVLCIATIYVRYKQVHALSPEENVIIKLNKAGLVLGILSCLGLSIVANFQKTTLFAA
HVSGAVLTFGMGSLYMFVQTILSYQMQPKIHGKQVFWIRLLLVIWCGVSALSMLTCSSVL
HSGNFGTDLEQKLHWNPEDKGYVLHMITTAAEWSMSFSFFGFFLTYIRDFQKISLRVEAN
LHGLTLYDTAPCPINNERTRLLSRDI
Function
Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1.
Tissue Specificity Expression is down-regulated in ovarian tumors (at protein level). Widely expressed with highest levels in placenta and heart. Expressed in the retina. Not detected in brain or thymus.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Classic Hodgkin lymphoma DISV1LU6 Strong Biomarker [1]
Cone-rod dystrophy 2 DISX2RWY Strong GermlineCausalMutation [2]
Cone-rod dystrophy 21 DISZFSXG Strong Autosomal recessive [2]
Inherited retinal dystrophy DISGGL77 Strong Genetic Variation [3]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [4]
Neoplasm DISZKGEW Strong Altered Expression [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [4]
Polycystic ovarian syndrome DISZ2BNG Strong Altered Expression [5]
Promyelocytic leukaemia DISYGG13 Strong Altered Expression [6]
Retinoblastoma DISVPNPB Strong Biomarker [7]
Tuberculosis DIS2YIMD Strong Biomarker [8]
Retinopathy DISB4B0F moderate Genetic Variation [3]
Cone-rod dystrophy DISY9RWN Supportive Autosomal dominant [2]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [9]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [10]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [11]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [12]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [13]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of DNA damage-regulated autophagy modulator protein 2 (DRAM2). [14]
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⏷ Show the Full List of 6 Drug(s)

References

1 Estrogen receptor ligation inhibits Hodgkin lymphoma growth by inducing autophagy.Oncotarget. 2017 Jan 31;8(5):8522-8535. doi: 10.18632/oncotarget.14338.
2 Biallelic mutations in the autophagy regulator DRAM2 cause retinal dystrophy with early macular involvement. Am J Hum Genet. 2015 Jun 4;96(6):948-54. doi: 10.1016/j.ajhg.2015.04.006. Epub 2015 May 14.
3 Disease Expression in Autosomal Recessive Retinal Dystrophy Associated With Mutations in the DRAM2 Gene.Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8083-90. doi: 10.1167/iovs.15-17604.
4 DRAM2 acts as an oncogene in non-small cell lung cancer and suppresses the expression of p53.J Exp Clin Cancer Res. 2019 Feb 12;38(1):72. doi: 10.1186/s13046-019-1068-4.
5 Different protein expression patterns associated with polycystic ovary syndrome in human follicular fluid during controlled ovarian hyperstimulation.Reprod Fertil Dev. 2012;24(7):893-904. doi: 10.1071/RD11201.
6 MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy-lysosomal pathway in acute promyelocytic leukemia.Autophagy. 2014 Oct 1;10(10):1726-37. doi: 10.4161/auto.29592. Epub 2014 Jul 18.
7 MicroRNA-125b promotes tumor growth and suppresses apoptosis by targeting DRAM2 in retinoblastoma.Eye (Lond). 2016 Dec;30(12):1630-1638. doi: 10.1038/eye.2016.189. Epub 2016 Aug 12.
8 MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2.Autophagy. 2017 Feb;13(2):423-441. doi: 10.1080/15548627.2016.1241922. Epub 2016 Oct 20.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
11 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
12 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
13 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
14 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.