Details of Drug Off-Target (DOT)

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

• DOT Name: Doublecortin domain-containing protein 1 (DCDC1)
• Synonyms: Doublecortin domain-containing 5 protein
• Gene Name: DCDC1
• Related Disease:
  Esophageal squamous cell carcinoma
  Major depressive disorder
• UniProt ID: DCDC1_HUMAN
• Sequence:
  MAKTGAEDHREALSQSSLSLLTEAMEVLQQSSPEGTLDGNTVNPIYKYILNDLPREFMSS
  QAKAVIKTTDDYLQSQFGPNRLVHSAAVSEGSGLQDCSTHQTASDHSHDEISDLDSYKSN
  SKNNSCSISASKRNRPVSAPVGQLRVAEFSSLKFQSARNWQKLSQRHKLQPRVIKVTAYK
  NGSRTVFARVTVPTITLLLEECTEKLNLNMAARRVFLADGKEALEPEDIPHEADVYVSTG
  EPFLNPFKKIKDHLLLIKKVTWTMNGLMLPTDIKRRKTKPVLSIRMKKLTERTSVRILFF
  KNGMGQDGHEITVGKETMKKVLDTCTIRMNLNLPARYFYDLYGRKIEDISKVPLLEKCLQ
  NSITPLRGLLWVSKGEGFSPSGAKMYIQGVLLALYQRLKSAKKYYKQLNLVMNEQKEKIT
  EKVILSMTAKEHHKEQEEVSRLIDELQTAIKSNIGHLCKLGPQLQAEQEQFSSYVYQHIK
  SLPANTLVPGGLQLKVFENGKNTGEISVGISKKDLGSDSPIQTDHMMERLLLKIHQRLQG
  SSINPPGLNYSSMRLFDENGQEIKNPLSLKNEQKIWVSYGRAYRSPLNLALGLTFDRVSA
  FARGDIMVAYKTFLDPNAVLLPGCGNWEVCEGFPINFNCTSQQIPDQFEKVDLENHFLQN
  KVDPNIVLHASVSIGKWSFSGSEASSRSQIAPSILWPVASVWLITKTGMILSRAITQGCL
  AIGHPIRVKAAEGTSLEGYKLILQKRHSGDDSQKWVFGTDGCIYSKAYPQFVLTYLEELN
  AQVDVTQTEYHIHHGAWTTAHQEHGRNLAEEVLQESASNLGLKQLPEPSDTHLMPEGSLE
  ETGELTVALVRKLEEKHPKASAQRWAIKHEGTSKPGQWKHSRVENPLWNKLTYMWPVLPS
  GQLNEEFDWPIQGLLVPSSPPMKKPICKTTEPYAPVRLRVLQNGEKNKNRSVTILGPDIS
  PGRKTQCTEILNLPSAARRLYNEKGKEIFALKDLQRDELVYVSCGELWINPDLSIAQQKK
  QIFLRNLESDIAKIQIFCSTHKIEALVLEVQSDIVSGSKLAVHKPVAIFGEEKQVTEPEE
  KQMQEDPLTTENASSEILDSHVRAHLRMKACHTLPRYAWQETSHDFDEDDSLPKKTEKGL
  FENVEPQKKHSCSPKHSKLHKHCHQQFEYRDGQIISHAAPQLVLGVQGPNLRSGMEVVLV
  EKKSDGSHQRWIHQEDSRTFHLVSNPDLVLAVSMTKTRNEVCGYPVIVQKYKPYNNGAAN
  QKWHYMKNIKALVAFHSTALDKEITSANYAGVCTSSVIKEENIDQPGYCYLSPDGKRKTM
  LCLACGQSMRTEKGLKQLLPGVPFLCISGTKTQKPFLQGPFKVISVAEVDLSCDKAEKTL
  SYYQARLLSLRMKTCTQAASHSGMAATHQKAVKIIAYKNGDGYRNGKLIVAGTFPMLLTE
  CTEQLGLARAASKVYTKDGTPIFTLRDLVLWALDESFLQRDSEKQKQDAAPVGKEQIIVE
  KNPRMKVKNRLFAKSVTSDSLDGIDKSLLTLILRNPIAIWVSCGEPFLPPNALQKAEKLE
  KQNWLKKDRILADLDTMRHKMRQLKGRRVAACQPATMVPTKSPVQPVVVEGGWTEQTQQE
  IKLMELIRHTEAHLSEIQEMESKINFPIATKRIAVKPSNLYKQPNTKRVWIYLNGGRPED
  GTYAWGKTISELLQDCSSRLKMTHPARALYTPSGEPIQSWDDIERDMVICVSMGHGFKTP
  KELKQLMEIRANYARIRRQQGPQATDIVVSPSTKLLSLAHLHN
• Function: Microtubule-binding protein which plays an important role in mediating dynein-dependent transport of RAB8A-positive vesicles to the midbody during cytokinesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]

2 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 Doublecortin domain-containing protein 1 (DCDC1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Doublecortin domain-containing protein 1 (DCDC1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Doublecortin domain-containing protein 1 (DCDC1).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Doublecortin domain-containing protein 1 (DCDC1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Doublecortin domain-containing protein 1 (DCDC1).	[6]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Doublecortin domain-containing protein 1 (DCDC1).	[8]

References

• [1] Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance.Sci Rep. 2017 Nov 10;7(1):15324. doi: 10.1038/s41598-017-14909-5.
• [2] Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] 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.
• [8] 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.