Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGMET92)

• DOT Name: BBSome-interacting protein 1 (BBIP1)
• Synonyms: BBSome-interacting protein of 10 kDa
• Gene Name: BBIP1
• Related Disease:
  Bardet-Biedl syndrome 18
  Bardet biedl syndrome
• UniProt ID: BBIP1_HUMAN
• PDB ID: 6XT9
• Pfam ID: PF14777
• Sequence:
  MLKAAAKRPELSGKNTISNNSDMAEVKSMFREVLPKQGPLFVEDIMTMVLCKPKLLPLKS
  LTLEKLEKMHQAAQNTIRQQEMAEKDQRQITH
• Function: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. Required for primary cilia assembly and BBSome stability. Regulates cytoplasmic microtubule stability and acetylation.
• Reactome Pathway: BBSome-mediated cargo-targeting to cilium (R-HSA-5620922)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bardet-Biedl syndrome 18	DISI2YY4	Strong	Autosomal recessive	[1]
Bardet biedl syndrome	DISTBNZW	Supportive	Autosomal recessive	[1]

1 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 BBSome-interacting protein 1 (BBIP1).	[2]

6 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 BBSome-interacting protein 1 (BBIP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of BBSome-interacting protein 1 (BBIP1).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of BBSome-interacting protein 1 (BBIP1).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BBSome-interacting protein 1 (BBIP1).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of BBSome-interacting protein 1 (BBIP1).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of BBSome-interacting protein 1 (BBIP1).	[7]

References

• [1] Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J Med Genet. 2014 Feb;51(2):132-6. doi: 10.1136/jmedgenet-2013-101785. Epub 2013 Sep 11.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.