Details of Drug Off-Target (DOT)

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
• 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]

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]

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.