Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9J7RLC)

• DOT Name: MAP3K7 C-terminal-like protein (MAP3K7CL)
• Synonyms: TAK1-like protein
• Gene Name: MAP3K7CL
• Related Disease:
  Atrial fibrillation
  Cardiac failure
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Dermatofibrosarcoma protuberans
  Tuberculosis
  Breast cancer
  Breast carcinoma
• UniProt ID: M3KCL_HUMAN
• Sequence:
  MISTARVPADKPVRIAFSLNDASDDTPPEDSIPLVFPELDQQLQPLPPCHDSEESMEVFK
  QHCQIAEEYHEVKKEITLLEQRKKELIAKLDQAEKEKVDAAELVREFEALTEENRTLRLA
  QSQCVEQLEKLRIQYQKRQGSS
• Tissue Specificity: Detected in lung and peripheral blood leukocytes. Expressed predominantly in peripheral blood leukocytes and ubiquitously in adult and fetal tissues. Also expressed strongly in breast carcinoma GI-101, colon adenocarcinoma GI-112, and prostatic adenocarcinoma PC3.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Genetic Variation	[1]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[2]
Dermatofibrosarcoma protuberans	DIS4OCQM	Strong	Biomarker	[3]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[5]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[5]

9 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 MAP3K7 C-terminal-like protein (MAP3K7CL).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MAP3K7 C-terminal-like protein (MAP3K7CL).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of MAP3K7 C-terminal-like protein (MAP3K7CL).	[13]

References

• [1] Phenotypic Refinement of Heart Failure in a National Biobank Facilitates Genetic Discovery.Circulation. 2019 Jan 22;139(4):489-501. doi: 10.1161/CIRCULATIONAHA.118.035774. Epub 2018 Nov 11.
• [2] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [3] A novel MAP3K7CL-ERG fusion in a molecularly confirmed case of dermatofibrosarcoma protuberans with fibrosarcomatous transformation.J Cutan Pathol. 2019 Jul;46(7):532-537. doi: 10.1111/cup.13469. Epub 2019 May 3.
• [4] Oxidization of TGF-activated kinase by MPT53 is required for immunity to Mycobacterium tuberculosis.Nat Microbiol. 2019 Aug;4(8):1378-1388. doi: 10.1038/s41564-019-0436-3. Epub 2019 May 20.
• [5] Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.PLoS Genet. 2012;8(2):e1002532. doi: 10.1371/journal.pgen.1002532. Epub 2012 Feb 23.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] 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.
• [8] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [12] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] 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.