Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLN65IU)

• DOT Name: BICD family-like cargo adapter 1 (BICDL1)
• Synonyms: Bicaudal D-related protein 1; BICD-related protein 1; BICDR-1; Coiled-coil domain-containing protein 64A; CCDC64A
• Gene Name: BICDL1
• UniProt ID: BICL1_HUMAN
• Sequence:
  MSAFCLGLVGRASAPAEPDSACCMELPAAAGDAVRSPAAAAALIFPGGSGELELALEEEL
  ALLAAGERPSDPGEHPQAEPGSLAEGAGPQPPPSQDPELLSVIRQKEKDLVLAARLGKAL
  LERNQDMSRQYEQMHKELTDKLEHLEQEKHELRRRFENREGEWEGRVSELESDVKQLQDE
  LERQQIHLREADREKSRAVQELSEQNQRLLDQLSRASEVERQLSMQVHALREDFREKNSS
  TNQHIIRLESLQAEIKMLSDRKRELEHRLSATLEENDLLQGTVEELQDRVLILERQGHDK
  DLQLHQSQLELQEVRLSCRQLQVKVEELTEERSLQSSAATSTSLLSEIEQSMEAEELEQE
  REQLRLQLWEAYCQVRYLCSHLRGNDSADSAVSTDSSMDESSETSSAKDVPAGSLRTALN
  ELKRLIQSIVDGMEPTVTLLSVEMTALKEERDRLRVTSEDKEPKEQLQKAIRDRDEAIAK
  KNAVELELAKCRMDMMSLNSQLLDAIQQKLNLSQQLEAWQDDMHRVIDRQLMDTHLKERS
  QPAAALCRGHSAGRGDEPSIAEGKRLFSFFRKI
• Function: Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor. Component of secretory vesicle machinery in developing neurons that acts as a regulator of neurite outgrowth. Regulates the secretory vesicle transport by controlling the accumulation of Rab6-containing secretory vesicles in the pericentrosomal region restricting anterograde secretory transport during the early phase of neuronal differentiation, thereby inhibiting neuritogenesis.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BICD family-like cargo adapter 1 (BICDL1).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of BICD family-like cargo adapter 1 (BICDL1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BICD family-like cargo adapter 1 (BICDL1).	[10]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [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] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.