Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT39FSH8)

• DOT Name: Centrosomal protein of 162 kDa (CEP162)
• Synonyms: Cep162; Protein QN1 homolog
• Gene Name: CEP162
• UniProt ID: CE162_HUMAN
• Sequence:
  MANCSQEELDEEFEQFMKELSDDSFENSDKTARQSKKEMKKKDTVPWWITEDDFKDDGLL
  GTNVSYLKTKKTSQPVMEIEEESAEKIQFLKSSGTSLLSTDSLETNELVVSELNHSSLGV
  GLDTLEEQEEKEQFFARLEKGLTSSIDYSRLNKELDSNDSTHFKALHSNQANAELTDDEH
  ENESKHEELAENYSDDFEDEYVGAPLTTKDEEMPSKENSKSEKISVPKQEEEKTGMLANV
  VLLDSLDSVAEVNLDEQDKITPKPRCLPEMTENEMTGTGVSYGQSSSDVEALHQAYCHIA
  HSLGDEDKQKIESNTVEDIKSSVKGHPQENEENSKNISTMESDLPTVEELMKPIRIDSFG
  ISGFDLQPVSSEKVAERKETEFFSSLPLKMNPNILSQDSQHVNLFFDKNDENVILQKTTN
  ESMENSCPQVTEVTATEEHVDKMYLNILRKKITVNSSSLSQDDKINKTYRSQLSSEEEGA
  VMGKQVPYKKARSAPPLLKRKPQSGLYASVRSSGYGKPSSPLKMFSTLEKKTSEDIIKSK
  NLRSISTSNQPRKKEILSGTKLIKPAALDKPAHKTESCLSTRKKSENPTETDSCIQFQTD
  SLGYCGENKEKKLLMFKRVQEAEDKWRGAQALIEQIKATFSEKEKELENKLEELKKQQEK
  ELFKLNQDNYILQAKLSSFEETNKKQRWLHFGEAADPVTGEKLKQIQKEIQEQETLLQGY
  QQENERLYNQVKDLQEQNKKNEERMFKENQSLFSEVASLKEQMHKSRFLSQVVEDSEPTR
  NQNFTDLLAELRMAQKEKDSLLEDIKRLKQDKQALEVDFEKMKKERDQAKDQIAYVTGEK
  LYEIKILEETHKQEISRLQKRLQWYAENQELLDKDALRLREANEEIEKLKLEIEKLKAES
  GNPSIRQKIRLKDKAADAKKIQDLERQVKEMEGILKRRYPNSLPALILAASAAGDTVDKN
  TVEFMEKRIKKLEADLEGKDEDAKKSLRTMEQQFQKMKIQYEQRLEQQEQLLACKLNQHD
  SPRIKALEKELDDIKEAHQITVRNLEAEIDVLKHQNAELDVKKNDKDDEDFQSIEFQVEQ
  AHAKAKLVRLNEELAAKKREIQDLSKTVERLQKDRRMMLSNQNSKGREEMSAKRAKKDVL
  HSSKGNANSFPGTLDSKLYQPHTFTDSHVSEVLQENYRLKNELEGLISEKNELKMKSEAV
  MNQFENSMRRVKEDTAAHIASLKASHQREIEKLLCQNAVENSSSKVAELNRKIATQEVLI
  RHFQSQVNELQSKQESLVVSEVREEILQKEITKLLEELREAKENHTPEMKHFVGLEKKIK
  QMEMRHAQREQELQQIIQQTHQVVETEQNKEVEKWKRLAQLKNRELEKFRTELDSILDVL
  RELHRQGVVVPVAFADEMNAPEY
• Function: Required to promote assembly of the transition zone in primary cilia. Acts by specifically recognizing and binding the axonemal microtubule. Localizes to the distal ends of centrioles before ciliogenesis and directly binds to axonemal microtubule, thereby promoting and restricting transition zone formation specifically at the cilia base. Required to mediate CEP290 association with microtubules.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Centrosomal protein of 162 kDa (CEP162).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Centrosomal protein of 162 kDa (CEP162).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Centrosomal protein of 162 kDa (CEP162).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centrosomal protein of 162 kDa (CEP162).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centrosomal protein of 162 kDa (CEP162).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centrosomal protein of 162 kDa (CEP162).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Centrosomal protein of 162 kDa (CEP162).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Centrosomal protein of 162 kDa (CEP162).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Centrosomal protein of 162 kDa (CEP162).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centrosomal protein of 162 kDa (CEP162).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Centrosomal protein of 162 kDa (CEP162).	[11]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.