Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2)
• Synonyms: Adhesion molecule in glia; AMOG; Sodium/potassium-dependent ATPase subunit beta-2
• Gene Name: ATP1B2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Malignant glioma
  Epithelial ovarian cancer
  Anaplastic astrocytoma
  Astrocytoma
  Adult glioblastoma
  Mixed glioma
• UniProt ID: AT1B2_HUMAN
• Pfam ID: PF00287
• Sequence:
  MVIQKEKKSCGQVVEEWKEFVWNPRTHQFMGRTGTSWAFILLFYLVFYGFLTAMFTLTMW
  VMLQTVSDHTPKYQDRLATPGLMIRPKTENLDVIVNVSDTESWDQHVQKLNKFLEPYNDS
  IQAQKNDVCRPGRYYEQPDNGVLNYPKRACQFNRTQLGNCSGIGDSTHYGYSTGQPCVFI
  KMNRVINFYAGANQSMNVTCAGKRDEDAENLGNFVMFPANGNIDLMYFPYYGKKFHVNYT
  QPLVAVKFLNVTPNVEVNVECRINAANIATDDERDKFAGRVAFKLRINKT
• Function: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.; Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
• KEGG Pathway:
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Cytoskeleton in muscle cells (hsa04820)
  Insulin secretion (hsa04911)
  Thyroid hormone synthesis (hsa04918)
  Thyroid hormone sig.ling pathway (hsa04919)
  Aldosterone synthesis and secretion (hsa04925)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Proximal tubule bicarbo.te reclamation (hsa04964)
  Salivary secretion (hsa04970)
  Gastric acid secretion (hsa04971)
  Pancreatic secretion (hsa04972)
  Carbohydrate digestion and absorption (hsa04973)
  Protein digestion and absorption (hsa04974)
  Bile secretion (hsa04976)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Ion homeostasis (R-HSA-5578775)
  Ion transport by P-type ATPases (R-HSA-936837)
  Potential therapeutics for SARS (R-HSA-9679191)
  Basigin interactions (R-HSA-210991)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[3]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Posttranslational Modification	[5]
Malignant glioma	DISFXKOV	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	moderate	Genetic Variation	[6]
Anaplastic astrocytoma	DISSBE0K	Disputed	Altered Expression	[5]
Astrocytoma	DISL3V18	Disputed	Altered Expression	[5]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[4]
Mixed glioma	DIS64UY3	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[8]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[16]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sodium/potassium-transporting ATPase subunit beta-2 (ATP1B2).	[12]

References

• [1] AMOG/beta2 and glioma invasion: does loss of AMOG make tumour cells run amok?.Neuropathol Appl Neurobiol. 2003 Aug;29(4):370-7. doi: 10.1046/j.1365-2990.2003.00473.x.
• [2] Comparative epigenomics of human and mouse mammary tumors.Genes Chromosomes Cancer. 2009 Jan;48(1):83-97. doi: 10.1002/gcc.20620.
• [3] Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.Nat Genet. 2014 Sep;46(9):1001-1006. doi: 10.1038/ng.3064. Epub 2014 Aug 17.
• [4] Targeting 2 subunit of Na(+)/K(+)-ATPase induces glioblastoma cell apoptosis through elevation of intracellular Ca(2).Am J Cancer Res. 2019 Jun 1;9(6):1293-1308. eCollection 2019.
• [5] Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction.Int J Cancer. 2006 Nov 15;119(10):2330-8. doi: 10.1002/ijc.22108.
• [6] Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study.BMC Cancer. 2007 Apr 5;7:60. doi: 10.1186/1471-2407-7-60.
• [7] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells. Int J Oncol. 2010 Nov;37(5):1297-305. doi: 10.3892/ijo_00000781.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] 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.