Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT144G80)

• DOT Name: Methionine aminopeptidase 1D, mitochondrial (METAP1D)
• Synonyms: MAP 1D; MetAP 1D; EC 3.4.11.18; Methionyl aminopeptidase type 1D, mitochondrial; Peptidase M 1D
• Gene Name: METAP1D
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Acute myelogenous leukaemia
• UniProt ID: MAP12_HUMAN
• EC Number: 3.4.11.18
• Pfam ID: PF00557
• Sequence:
  MAAPSGVHLLVRRGSHRIFSSPLNHIYLHKQSSSQQRRNFFFRRQRDISHSIVLPAAVSS
  AHPVPKHIKKPDYVTTGIVPDWGDSIEVKNEDQIQGLHQACQLARHVLLLAGKSLKVDMT
  TEEIDALVHREIISHNAYPSPLGYGGFPKSVCTSVNNVLCHGIPDSRPLQDGDIINIDVT
  VYYNGYHGDTSETFLVGNVDECGKKLVEVARRCRDEAIAACRAGAPFSVIGNTISHITHQ
  NGFQVCPHFVGHGIGSYFHGHPEIWHHANDSDLPMEEGMAFTIEPIITEGSPEFKVLEDA
  WTVVSLDNQRSAQFEHTVLITSRGAQILTKLPHEA
• Function: Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed. May play a role in colon tumorigenesis.
• Tissue Specificity: Overexpressed in colon cancer cell lines and colon tumors as compared to normal tissues (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Methionine aminopeptidase 1D, mitochondrial (METAP1D).	[9]

References

• [1] MAP1D, a novel methionine aminopeptidase family member is overexpressed in colon cancer.Oncogene. 2006 Jun 8;25(24):3471-8. doi: 10.1038/sj.onc.1209383. Epub 2006 Mar 27.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] 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.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.