Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8LQI1W)

• DOT Name: Leucine-rich repeat-containing protein 55 (LRRC55)
• Synonyms: BK channel auxiliary gamma subunit LRRC55
• Gene Name: LRRC55
• Related Disease: Type-1/2 diabetes
• UniProt ID: LRC55_HUMAN
• Pfam ID: PF13855
• Sequence:
  MGDTWAQLPWPGPPHPAMLLISLLLAAGLMHSDAGTSCPVLCTCRNQVVDCSSQRLFSVP
  PDLPMDTRNLSLAHNRITAVPPGYLTCYMELQVLDLHNNSLMELPRGLFLHAKRLAHLDL
  SYNNFSHVPADMFQEAHGLVHIDLSHNPWLRRVHPQAFQGLMQLRDLDLSYGGLAFLSLE
  ALEGLPGLVTLQIGGNPWVCGCTMEPLLKWLRNRIQRCTADSQLAECRGPPEVEGAPLFS
  LTEESFKACHLTLTLDDYLFIAFVGFVVSIASVATNFLLGITANCCHRWSKASEEEEI
• Function: Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium.
• Tissue Specificity: Mainly expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]

3 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 Leucine-rich repeat-containing protein 55 (LRRC55).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Leucine-rich repeat-containing protein 55 (LRRC55).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Leucine-rich repeat-containing protein 55 (LRRC55).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[3]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Leucine-rich repeat-containing protein 55 (LRRC55).	[7]

References

• [1] Lrrc55 is a novel prosurvival factor in pancreatic islets.Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E794-E804. doi: 10.1152/ajpendo.00028.2019. Epub 2019 Sep 17.
• [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] 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.
• [4] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [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] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.