Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT87X2EH)

• DOT Name: Small conductance calcium-activated potassium channel protein 1 (KCNN1)
• Synonyms: SK1; SKCa 1; SKCa1; KCa2.1
• Gene Name: KCNN1
• UniProt ID: KCNN1_HUMAN
• Pfam ID: PF02888 ; PF07885 ; PF03530
• Sequence:
  MNSHSYNGSVGRPLGSGPGALGRDPPDPEAGHPPQPPHSPGLQVVVAKSEPARPSPGSPR
  GQPQDQDDDEDDEEDEAGRQRASGKPSNVGHRLGHRRALFEKRKRLSDYALIFGMFGIVV
  MVTETELSWGVYTKESLYSFALKCLISLSTAILLGLVVLYHAREIQLFMVDNGADDWRIA
  MTCERVFLISLELAVCAIHPVPGHYRFTWTARLAFTYAPSVAEADVDVLLSIPMFLRLYL
  LGRVMLLHSKIFTDASSRSIGALNKITFNTRFVMKTLMTICPGTVLLVFSISSWIIAAWT
  VRVCERYHDKQEVTSNFLGAMWLISITFLSIGYGDMVPHTYCGKGVCLLTGIMGAGCTAL
  VVAVVARKLELTKAEKHVHNFMMDTQLTKRVKNAAANVLRETWLIYKHTRLVKKPDQARV
  RKHQRKFLQAIHQAQKLRSVKIEQGKLNDQANTLTDLAKTQTVMYDLVSELHAQHEELEA
  RLATLESRLDALGASLQALPGLIAQAIRPPPPPLPPRPGPGPQDQAARSSPCRWTPVAPS
  DCG
• Function: Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization.
• KEGG Pathway:
  Insulin secretion (hsa04911)
  GnRH secretion (hsa04929)
• Reactome Pathway: Ca2+ activated K+ channels (R-HSA-1296052)

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 Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[3]
Tubocurarine	DMBZIVP	Approved	Tubocurarine decreases the activity of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[4]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[6]
UCL1684	DMZNJFU	Investigative	UCL1684 decreases the activity of Small conductance calcium-activated potassium channel protein 1 (KCNN1).	[4]

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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells. Br J Pharmacol. 2000 Mar;129(5):991-9.
• [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] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.