Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTO6ZP4)

• DOT Name: Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)
• Synonyms: Sodium/potassium-dependent ATPase subunit beta-1
• Gene Name: ATP1B1
• Related Disease:
  Acute myelogenous leukaemia
  Clear cell renal carcinoma
  Drug dependence
  Essential hypertension
  Fuchs' endothelial dystrophy
  High blood pressure
  Kidney cancer
  Renal cell carcinoma
  Sensorineural hearing loss disorder
  Substance abuse
  Substance dependence
  Venous thromboembolism
  Von hippel-lindau disease
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Coronary heart disease
  Retinopathy
• UniProt ID: AT1B1_HUMAN
• PDB ID: 7E1Z; 7E20; 7E21; 8D3U; 8D3V; 8D3W; 8D3X; 8D3Y
• Pfam ID: PF00287
• Sequence:
  MARGKAKEEGSWKKFIWNSEKKEFLGRTGGSWFKILLFYVIFYGCLAGIFIGTIQVMLLT
  ISEFKPTYQDRVAPPGLTQIPQIQKTEISFRPNDPKSYEAYVLNIVRFLEKYKDSAQRDD
  MIFEDCGDVPSEPKERGDFNHERGERKVCRFKLEWLGNCSGLNDETYGYKEGKPCIIIKL
  NRVLGFKPKPPKNESLETYPVMKYNPNVLPVQCTGKRDEDKDKVGNVEYFGLGNSPGFPL
  QYYPYYGKLLQPKYLQPLLAVQFTNLTMDTEIRIECKAYGENIGYSEKDRFQGRFDVKIE
  VKS
• 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. Plays a role in innate immunity by enhancing virus-triggered induction of interferons (IFNs) and interferon stimulated genes (ISGs). Mechanistically, enhances the ubiquitination of TRAF3 and TRAF6 as well as the phosphorylation of TAK1 and TBK1 ; Involved in cell adhesion and establishing epithelial cell polarity.
• Tissue Specificity: Found in most tissues.
• 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

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Drug dependence	DIS9IXRC	Strong	Biomarker	[3]
Essential hypertension	DIS7WI98	Strong	Genetic Variation	[4]
Fuchs' endothelial dystrophy	DISL7TXC	Strong	Biomarker	[5]
High blood pressure	DISY2OHH	Strong	Biomarker	[6]
Kidney cancer	DISBIPKM	Strong	Altered Expression	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Posttranslational Modification	[7]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[8]
Substance abuse	DIS327VW	Strong	Biomarker	[3]
Substance dependence	DISDRAAR	Strong	Biomarker	[3]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[9]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	moderate	Biomarker	[10]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[10]
Castration-resistant prostate carcinoma	DISVGAE6	moderate	Genetic Variation	[11]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[12]
Retinopathy	DISB4B0F	moderate	Altered Expression	[13]

1 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/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[18]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[24]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[25]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[26]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[27]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[28]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[29]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[31]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[32]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[33]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1).	[28]

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