Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9TK2O)

• DOT Name: Trafficking protein particle complex subunit 14 (TRAPPC14)
• Synonyms: Microtubule-associated protein 11
• Gene Name: TRAPPC14
• Related Disease: Autosomal recessive primary microcephaly
• UniProt ID: TPC14_HUMAN
• Pfam ID: PF15806
• Sequence:
  MESQCDYSMYFPAVPLPPRAELAGDPGRYRALPRRNHLYLGETVRFLLVLRCRGGAGSGT
  GGGPGLGSRGAWAELATALAALASVSAGGGMPGGGGAGDQDSEPPGGGDPGGGGLFRGCS
  PLLTHGPGPATSGGATTLPVEEPIVSTDEVIFPLTVSLDRLPPGTPKAKIVVTVWKREIE
  APEVRDQGYLRLLQTRSPGETFRGEQSAFKAQVSTLLTLLPPPVLRCRQFTVAGKHLTVL
  KVLNSSSQEEISIWDIRILPNFNASYLPVMPDGSVLLVDNVCHQSGEVSMGSFCRLPGTS
  GCFPCPLNALEEHNFLFQLRGGEQPPPGAKEGLEVPLIAVVQWSTPKLPFTQSIYTHYRL
  PSVRLDRPCFVMTASCKSPVRTYERFTVTYTLLNNLQDFLAVRLVWTPEHAQAGKQLCEE
  ERRAMQAALDSVVCHTPLNNLGFSRKGSALTFSVAFQALRTGLFELSQHMKLKLQFTASV
  SHPPPEARPLSRKSSPSSPAVRDLVERHQASLGRSQSFSHQQPSRSHLMRSGSVMERRAI
  TPPVASPVGRPLYLPPDKAVLSLDKIAKRECKVLVVEPVK
• Function: Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether. TRAPP II complex has also GEF activity toward RAB1A. TRAPPC14 is dispensable for TRAPPII complex integrity but mediates RAB3IP preciliary vesicle trafficking to the mother centriole during ciliogenesis. Modulates YAP1 activity as transcriptional regulator.
• Tissue Specificity: Broadly expressed. High levels in brain, cerebellum, testis and whole blood.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive primary microcephaly	DIS29IE3	Supportive	Autosomal recessive	[1]

2 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 Trafficking protein particle complex subunit 14 (TRAPPC14).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Trafficking protein particle complex subunit 14 (TRAPPC14).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Trafficking protein particle complex subunit 14 (TRAPPC14).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Trafficking protein particle complex subunit 14 (TRAPPC14).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Trafficking protein particle complex subunit 14 (TRAPPC14).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Trafficking protein particle complex subunit 14 (TRAPPC14).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Trafficking protein particle complex subunit 14 (TRAPPC14).	[7]

References

• [1] Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish. Brain. 2019 Mar 1;142(3):574-585. doi: 10.1093/brain/awz004.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] 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.