Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2H3MRD)

• DOT Name: Janus kinase and microtubule-interacting protein 2 (JAKMIP2)
• Synonyms: CTCL tumor antigen HD-CL-04; Neuroendocrine long coiled-coil protein 1
• Gene Name: JAKMIP2
• Related Disease:
  Choriocarcinoma
  Complete hydatidiform mole
  Esophageal squamous cell carcinoma
  Graves disease
  Melanoma
  Narcolepsy
• UniProt ID: JKIP2_HUMAN
• Pfam ID: PF16034
• Sequence:
  MSKKGRNKGEKPEALIVALQAANEDLRTKLTDIQIELHQEKSKVSKLEREKTQEAKRIRE
  LEQRKHTVLVTELKAKLHEEKMKELQAVRENLIKQHEQEMSRTVKVRDGEIQRLKSALCA
  LRDGSSDKVRTALTIEAREEARKLFDTERLKLLQEIADLKTAKKQVDEALSNMIQADKIK
  AGDLRSEHQSHQEAISKIKWESERDIRRLMDEIKAKDRIIFSLEKELETQTGYVQKLQLQ
  KEALDEQLFLVKEAECNMSSPKREIPGRAGDGSEHCSSPDLRRNQKRIAELNATIRKLED
  RNTLLGDERNELLKRVRETEKQCKPLLERNKCLAKRNDELMVSLQRMEEKLKAVTKENSE
  MREKITSHPPLKKLKSLNDLDQANEEQETEFLKLQVIEQQNIIDELTRDREKLIRRRKHR
  RSSKPIKRPVLDPFIGYDEDSMDSETSSMASFRTDRTPATPDDDLDESLAAEESELRFRQ
  LTKEYQALQRAYALLQEQTGGIIDAEREAKAQEQLQAEVLRYKAKIEDLEATLAQKGQDS
  HWVEDKQLFIKRNQELLEKIEKQEAENHRLQQELQDARDQNELLEFRNLELEERERRSPP
  FNLQIHPFSDGVSALQIYCMKEGVKDVNIPDLIKQLDILGDNGNLRNEEQVAIIQASTVL
  SLAEKWIQQIEGAEAALHQKMMELESDMEQFCKIKGYLEEELDYRKQALDQAYMRIQELE
  ATLYNALQQETVIKFGELLSEKQQEELRTAVEKLRRQMLRKSREYDCQILQERMELLQQA
  HQRIRDLEDKTDIQKRQIKDLEEKSNRKHG
• Tissue Specificity: Highly expressed in brain, moderately expressed in thymus, spleen and lung, and weakly expressed in kidney, liver and peripheral blood lymphocytes. Also expressed in adrenal and pituitary glands, as well as testis.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[1]
Complete hydatidiform mole	DIS5QPI0	Strong	Altered Expression	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[3]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[4]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[6]

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 Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Janus kinase and microtubule-interacting protein 2 (JAKMIP2).	[15]

References

• [1] NECC1, a candidate choriocarcinoma suppressor gene that encodes a homeodomain consensus motif.Genomics. 2003 Jan;81(1):15-25. doi: 10.1016/s0888-7543(02)00011-3.
• [2] Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application.Best Pract Res Clin Obstet Gynaecol. 2003 Dec;17(6):827-36. doi: 10.1016/s1521-6934(03)00096-8.
• [3] HOP/OB1/NECC1 promoter DNA is frequently hypermethylated and involved in tumorigenic ability in esophageal squamous cell carcinoma.Mol Cancer Res. 2008 Jan;6(1):31-41. doi: 10.1158/1541-7786.MCR-07-0213.
• [4] Linkage Analysis of the Chromosome 5q31-33 Region Identifies JAKMIP2 as a Risk Factor for Graves' Disease in the Chinese Han Population.Med Sci Monit. 2019 Feb 23;25:1439-1451. doi: 10.12659/MSM.911489.
• [5] Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.Nat Genet. 2012 Sep;44(9):1006-14. doi: 10.1038/ng.2359. Epub 2012 Jul 29.
• [6] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [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.