Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP983W8)

• DOT Name: Histone-lysine N-methyltransferase MECOM (MECOM)
• Synonyms: EC 2.1.1.367; Ecotropic virus integration site 1 protein homolog; EVI-1; MDS1 and EVI1 complex locus protein; Myelodysplasia syndrome 1 protein; Myelodysplasia syndrome-associated protein 1
• Gene Name: MECOM
• Related Disease:
  Epithelial ovarian cancer
  MECOM-associated syndrome
  Radioulnar synostosis with amegakaryocytic thrombocytopenia 2
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute megakaryoblastic leukemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Childhood acute megakaryoblastic leukemia
  Childhood myelodysplastic syndrome
  Chronic myelomonocytic leukaemia
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congenital radioulnar synostosis
  Endometrial carcinoma
  Familial prostate carcinoma
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Myelodysplastic syndrome
  Myeloid leukaemia
  Myeloproliferative neoplasm
  Nasopharyngeal carcinoma
  Osteoporosis
  Otitis media
  Ovarian neoplasm
  Promyelocytic leukaemia
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Pancytopenia
  Triple negative breast cancer
  Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome
  Acute monocytic leukemia
  Anemia
  Breast neoplasm
  Colonic neoplasm
  Fanconi's anemia
  Lymphoid leukemia
  Ovarian cancer
• UniProt ID: MECOM_HUMAN
• PDB ID: 6BW3
• EC Number: 2.1.1.367
• Pfam ID: PF21549 ; PF00096 ; PF13912
• Sequence:
  MRSKGRARKLATNNECVYGNYPEIPLEEMPDADGVASTPSLNIQEPCSPATSSEAFTPKE
  GSPYKAPIYIPDDIPIPAEFELRESNMPGAGLGIWTKRKIEVGEKFGPYVGEQRSNLKDP
  SYGWEILDEFYNVKFCIDASQPDVGSWLKYIRFAGCYDQHNLVACQINDQIFYRVVADIA
  PGEELLLFMKSEDYPHETMAPDIHEERQYRCEDCDQLFESKAELADHQKFPCSTPHSAFS
  MVEEDFQQKLESENDLQEIHTIQECKECDQVFPDLQSLEKHMLSHTEEREYKCDQCPKAF
  NWKSNLIRHQMSHDSGKHYECENCAKVFTDPSNLQRHIRSQHVGARAHACPECGKTFATS
  SGLKQHKHIHSSVKPFICEVCHKSYTQFSNLCRHKRMHADCRTQIKCKDCGQMFSTTSSL
  NKHRRFCEGKNHFAAGGFFGQGISLPGTPAMDKTSMVNMSHANPGLADYFGANRHPAGLT
  FPTAPGFSFSFPGLFPSGLYHRPPLIPASSPVKGLSSTEQTNKSQSPLMTHPQILPATQD
  ILKALSKHPSVGDNKPVELQPERSSEERPFEKISDQSESSDLDDVSTPSGSDLETTSGSD
  LESDIESDKEKFKENGKMFKDKVSPLQNLASINNKKEYSNHSIFSPSLEEQTAVSGAVND
  SIKAIASIAEKYFGSTGLVGLQDKKVGALPYPSMFPLPFFPAFSQSMYPFPDRDLRSLPL
  KMEPQSPGEVKKLQKGSSESPFDLTTKRKDEKPLTPVPSKPPVTPATSQDQPLDLSMGSR
  SRASGTKLTEPRKNHVFGGKKGSNVESRPASDGSLQHARPTPFFMDPIYRVEKRKLTDPL
  EALKEKYLRPSPGFLFHPQMSAIENMAEKLESFSALKPEASELLQSVPSMFNFRAPPNAL
  PENLLRKGKERYTCRYCGKIFPRSANLTRHLRTHTGEQPYRCKYCDRSFSISSNLQRHVR
  NIHNKEKPFKCHLCDRCFGQQTNLDRHLKKHENGNMSGTATSSPHSELESTGAILDDKED
  AYFTEIRNFIGNSNHGSQSPRNVEERMNGSHFKDEKALVTSQNSDLLDDEEVEDEVLLDE
  EDEDNDITGKTGKEPVTSNLHEGNPEDDYEETSALEMSCKTSPVRYKEEEYKSGLSALDH
  IRHFTDSLKMRKMEDNQYSEAELSSFSTSHVPEELKQPLHRKSKSQAYAMMLSLSDKESL
  HSTSHSSSNVWHSMARAAAESSAIQSISHV
• Function: [Isoform 1]: Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis; [Isoform 7]: Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation. Likely to be one of the primary histone methyltransferases along with PRDM16 that direct cytoplasmic H3K9me1 methylation.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
  MAPK sig.ling pathway (hsa04010)
  Pathways in cancer (hsa05200)
  Chronic myeloid leukemia (hsa05220)
• Reactome Pathway:
  Regulation of PTEN gene transcription (R-HSA-8943724)
  PKMTs methylate histone lysines (R-HSA-3214841)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[1]
MECOM-associated syndrome	DISOBLXY	Definitive	Autosomal dominant	[2]
Radioulnar synostosis with amegakaryocytic thrombocytopenia 2	DISTGOYP	Definitive	Autosomal dominant	[3]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[8]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Biomarker	[4]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[9]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[12]
Congenital radioulnar synostosis	DISF96QX	Strong	Genetic Variation	[13]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[14]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[15]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[17]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[18]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[19]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Genetic Variation	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[6]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[21]
Otitis media	DISGZDUO	Strong	Biomarker	[22]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[23]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[23]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[15]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	moderate	Genetic Variation	[24]
Pancytopenia	DISVKEHV	moderate	Genetic Variation	[25]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[26]
Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome	DISBKMHA	Supportive	Autosomal dominant	[27]
Acute monocytic leukemia	DIS28NEL	Limited	Genetic Variation	[28]
Anemia	DISTVL0C	Limited	Biomarker	[29]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[23]
Colonic neoplasm	DISSZ04P	Limited	Biomarker	[23]
Fanconi's anemia	DISGW6Q8	Limited	Genetic Variation	[25]
Lymphoid leukemia	DIS65TYQ	Limited	Biomarker	[23]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[23]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Histone-lysine N-methyltransferase MECOM (MECOM) affects the response to substance of Temozolomide.	[55]
DTI-015	DMXZRW0	Approved	Histone-lysine N-methyltransferase MECOM (MECOM) affects the response to substance of DTI-015.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Histone-lysine N-methyltransferase MECOM (MECOM).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Histone-lysine N-methyltransferase MECOM (MECOM).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Histone-lysine N-methyltransferase MECOM (MECOM).	[47]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Histone-lysine N-methyltransferase MECOM (MECOM).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[40]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[41]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[42]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[43]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[44]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[45]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[45]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[49]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[51]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[52]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[53]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone decreases the expression of Histone-lysine N-methyltransferase MECOM (MECOM).	[54]

References

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