Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYOMO4G)

• DOT Name: KxDL motif-containing protein 1 (KXD1)
• Gene Name: KXD1
• UniProt ID: KXDL1_HUMAN
• Pfam ID: PF10241
• Sequence:
  MDLPDSASRVFCGRILSMVNTDDVNAIILAQKNMLDRFEKTNEMLLNFNNLSSARLQQMS
  ERFLHHTRTLVEMKRDLDSIFRRIRTLKGKLARQHPEAFSHIPEASFLEEEDEDPIPPST
  TTTIATSEQSTGSCDTSPDTVSPSLSPGFEDLSHVQPGSPAINGRSQTDDEEMTGE
• Function: As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. May be involved in the biogenesis of lysosome-related organelles such as melanosomes.

Molecular Interaction Atlas (MIA) of This DOT

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 KxDL motif-containing protein 1 (KXD1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of KxDL motif-containing protein 1 (KXD1).	[5]

4 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 KxDL motif-containing protein 1 (KXD1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of KxDL motif-containing protein 1 (KXD1).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of KxDL motif-containing protein 1 (KXD1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of KxDL motif-containing protein 1 (KXD1).	[6]

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] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.