Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium/hydrogen exchanger 2 (SLC9A2)
• Synonyms: Na(+)/H(+) exchanger 2; NHE-2; Solute carrier family 9 member 2
• Gene Name: SLC9A2
• UniProt ID: SL9A2_HUMAN
• Pfam ID: PF00999 ; PF16644
• Sequence:
  MEPLGNWRSLRAPLPPMLLLLLLQVAGPVGALAETLLNAPRAMGTSSSPPSPASVVAPGT
  TLFEESRLPVFTLDYPHVQIPFEITLWILLASLAKIGFHLYHKLPTIVPESCLLIMVGLL
  LGGIIFGVDEKSPPAMKTDVFFLYLLPPIVLDAGYFMPTRPFFENIGTIFWYAVVGTLWN
  SIGIGVSLFGICQIEAFGLSDITLLQNLLFGSLISAVDPVAVLAVFENIHVNEQLYILVF
  GESLLNDAVTVVLYNLFKSFCQMKTIETIDVFAGIANFFVVGIGGVLIGIFLGFIAAFTT
  RFTHNIRVIEPLFVFLYSYLSYITAEMFHLSGIMAITACAMTMNKYVEENVSQKSYTTIK
  YFMKMLSSVSETLIFIFMGVSTVGKNHEWNWAFVCFTLAFCLMWRALGVFVLTQVINRFR
  TIPLTFKDQFIIAYGGLRGAICFALVFLLPAAVFPRKKLFITAAIVVIFFTVFILGITIR
  PLVEFLDVKRSNKKQQAVSEEIYCRLFDHVKTGIEDVCGHWGHNFWRDKFKKFDDKYLRK
  LLIRENQPKSSIVSLYKKLEIKHAIEMAETGMISTVPTFASLNDCREEKIRKVTSSETDE
  IRELLSRNLYQIRQRTLSYNRHSLTADTSERQAKEILIRRRHSLRESIRKDSSLNREHRA
  STSTSRYLSLPKNTKLPEKLQKRRTISIADGNSSDSDADAGTTVLNLQPRARRFLPEQFS
  KKSPQSYKMEWKNEVDVDSGRDMPSTPPTPHSREKGTQTSGLLQQPLLSKDQSGSEREDS
  LTEGIPPKPPPRLVWRASEPGSRKARFGSEKP
• Function: Plasma membrane Na(+)/H(+) antiporter. Mediates the electroneutral exchange of intracellular H(+) ions for extracellular Na(+). Major apical Na(+)/H(+) exchanger in the base of the colonic crypt. Controls in the colonic crypt intracellular pH (pHi) to direct colonic epithelial cell differentiation into the absorptive enterocyte lineage at the expense of the secretory lineage.
• Tissue Specificity: Expressed in skeletal muscle, colon and kidney. Lower levels in the testis, prostate, ovary, and small intestine . In the distal colon, expressed along the cryptal axis .
• Reactome Pathway: Sodium/Proton exchangers (R-HSA-425986)

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 Sodium/hydrogen exchanger 2 (SLC9A2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium/hydrogen exchanger 2 (SLC9A2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sodium/hydrogen exchanger 2 (SLC9A2).	[2]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Sodium/hydrogen exchanger 2 (SLC9A2).	[3]

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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [3] Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
• [4] 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.