Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5KV1OA)

• DOT Name: ATPase PAAT (C10ORF88)
• Synonyms: EC 3.6.1.-; Protein associated with ABC transporters; PAAT
• Gene Name: C10ORF88
• Related Disease:
  Breast cancer
  Breast carcinoma
  Glioma
• UniProt ID: PAAT_HUMAN
• EC Number: 3.6.1.-
• Pfam ID: PF14958
• Sequence:
  METRTEDGGLTRRPTLASSWDVAGGALTHSLLLTRAGLGPGDFDWEELLAPPAPGQDLVI
  LKRNHNNKDENPCFLYLRCGPDGGEEIASIGILSSARNMEVYLGEEYCGTSRGKNVCTVL
  DDSEHEKIILYKKNLKLESSTHACKIKLLSFGERQCVFISKVVVHMRSVFANSSTSSPAL
  GSRIDLDKVQTIMESMGSKLSPGAQQLMDMVRCQQRNCIPIGEQLQSVLGNSGYKHMIGL
  QSSSTLGTLNKSSSTPFPFRTGLTSGNVTENLQTYIDKSTQLPGGENSTKLDECKVMPQN
  HSFLENDLKNAMASFLPKKVSDNSNIPNSELLPFLQNLCSQVNHLHVGNKTECQENITKH
  GERILGVGMEEQSICSYLEKILSKNMELMEKKLMDYIDQRIHELQEHIDDKIALLLDLLQ
  NPNSPPTGIPLRHYDSGERLSNGER
• Function: ATPase that regulates mitochondrial ABC transporters ABCB7, ABCB8/MITOSUR and ABCB10. Regulates mitochondrial ferric concentration and heme biosynthesis and plays a role in the maintenance of mitochondrial homeostasis and cell survival.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]

7 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 ATPase PAAT (C10ORF88).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATPase PAAT (C10ORF88).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ATPase PAAT (C10ORF88).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATPase PAAT (C10ORF88).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of ATPase PAAT (C10ORF88).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ATPase PAAT (C10ORF88).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATPase PAAT (C10ORF88).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of ATPase PAAT (C10ORF88).	[9]

References

• [1] Common genetic variants in the vitamin D pathway including genome-wide associated variants are not associated with breast cancer risk among Chinese women.Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2313-6. doi: 10.1158/1055-9965.EPI-11-0704. Epub 2011 Aug 9.
• [2] An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome.Cancer Causes Control. 2012 Sep;23(9):1443-9. doi: 10.1007/s10552-012-0018-7. Epub 2012 Jun 28.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.