Details of Drug Off-Target (DOT)

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

• DOT Name: Janus kinase and microtubule-interacting protein 1 (JAKMIP1)
• Synonyms: GABA-B receptor-binding protein; Multiple alpha-helices and RNA-linker protein 1; Marlin-1
• Gene Name: JAKMIP1
• Related Disease:
  Autism
  Autism spectrum disorder
  Pervasive developmental disorder
  Retinitis pigmentosa
  Asthma
• UniProt ID: JKIP1_HUMAN
• Pfam ID: PF16034
• Sequence:
  MSKKGRSKGEKPEMETDAVQMANEELRAKLTSIQIEFQQEKSKVGKLRERLQEAKLEREQ
  EQRRHTAYISELKAKLHEEKTKELQALREGLIRQHEQEAARTAKIKEGELQRLQATLNVL
  RDGAADKVKTALLTEAREEARRAFDGERLRLQQEILELKAARKQAEEALSNCMQADKTKA
  ADLRAAYQAHQDEVHRIKRECERDIRRLMDEIKGKDRVILALEKELGVQAGQTQKLLLQK
  EALDEQLVQVKEAERHHSSPKRELPPGIGDMVELMGVQDQHMDERDVRRFQLKIAELNSV
  IRKLEDRNTLLADERNELLKRSRETEVQLKPLVEKNKRMNKKNEDLLQSIQRMEEKIKNL
  TRENVEMKEKLSAQASLKRHTSLNDLSLTRDEQEIEFLRLQVLEQQHVIDDLSLERERLL
  RSKRHRGKSLKPPKKHVVETFFGFDEESVDSETLSETSYNTDRTDRTPATPEEDLDDATA
  REEADLRFCQLTREYQALQRAYALLQEQVGGTLDAEREARTREQLQADLLRCQAKIEDLE
  KLLVEKGQDSKWVEEKQLLIRTNQDLLEKIYRLEMEENQLKNEMQDAKDQNELLEFRVLE
  LEVRDSICCKLSNGADILFEPKLKFM
• Function: Associates with microtubules and may play a role in the microtubule-dependent transport of the GABA-B receptor. May play a role in JAK1 signaling and regulate microtubule cytoskeleton rearrangements.
• Tissue Specificity: Predominantly expressed in neural tissues and lymphoid cells (at protein level). Isoform 2, isoform 3 and isoform 4 are specifically expressed in brain and retina. Isoform 1 and isoform 5 are also detected in liver, lung and skeletal muscle. Also detected in testis and to a lower extent spleen and intestine.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[3]
Asthma	DISW9QNS	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Janus kinase and microtubule-interacting protein 1 (JAKMIP1).	[10]

References

• [1] Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways.Hum Mol Genet. 2007 Jul 15;16(14):1682-98. doi: 10.1093/hmg/ddm116. Epub 2007 May 21.
• [2] Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics.Genome Med. 2016 Nov 1;8(1):105. doi: 10.1186/s13073-016-0359-z.
• [3] Identification and expression analysis of novel Jakmip1 transcripts.Gene. 2007 Nov 1;402(1-2):1-8. doi: 10.1016/j.gene.2007.07.001. Epub 2007 Jul 14.
• [4] Genome-wide association study of leukotriene modifier response in asthma.Pharmacogenomics J. 2016 Apr;16(2):151-7. doi: 10.1038/tpj.2015.34. Epub 2015 Jun 2.
• [5] 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.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.