Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8FB2F8)

• DOT Name: Mitochondrial nucleoid-associated protein 1 (MTNAP1)
• Synonyms: Cell migration-inducing gene 3 protein; Human lung cancer oncogene 8 protein; HLC-8; Protein C17orf80
• Gene Name: MTNAP1
• UniProt ID: CQ080_HUMAN
• Sequence:
  MSDNPPRMEVCPYCKKPFKRLKSHLPYCKMIGPTIPTDQKVYQSKPATLPRAKKMKGPIK
  DLIKAKGKELETENEERNSKLVVDKPEQTVKTFPLPAVGLERAATTKADKDIKNPIQPSF
  KMLKNTKPMTTFQEETKAQFYASEKTSPKRELAKDLPKSGESRCNPSEAGASLLVGSIEP
  SLSNQDRKYSSTLPNDVQTTSGDLKLDKIDPQRQELLVKLLDVPTGDCHISPKNVSDGVK
  RVRTLLSNERDSKGRDHLSGVPTDVTVTETPEKNTESLILSLKMSSLGKIQVMEKQEKGL
  TLGVETCGSKGNAEKSMSATEKQERTVMSHGCENFNTRDSVTGKESQGERPHLSLFIPRE
  TTYQFHSVSQSSSQSLASLATTFLQEKKAEAQNHHCVPDVKALMESPEGQLSLEPKSDSQ
  FQASHTGCQSPLCSAQRHTPQSPFTNHAAAAGRKTLRSCMGLEWFPELYPGYLGLGVLPG
  KPQCWNAMTQKPQLISPQGERLSQVSLLERSSTHIRSLEPPAGLTTSNFSLMRLLGAVQK
  GWIRCNTTIRKSGFGGITMLFTGYFVLCCSWSFRRLKKLCRPLPWKSTVPPCIGVAKTTG
  DCRSKTCLD
• Function: Critical regulator of mitochondrial DNA (mtDNA) abundance. Binds dsDNA throughout the mitochondrial genome without sequence specificity and controls mtDNA copy number by promoting its replication. Also plays important roles in mitochondrial metabolism and cell proliferation.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Mitochondrial nucleoid-associated protein 1 (MTNAP1).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.