Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM8EG6H)

• DOT Name: Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3)
• Synonyms: Na(+)/K(+) ATPase alpha-3 subunit; EC 7.2.2.13; Na(+)/K(+) ATPase alpha(III) subunit; Sodium pump subunit alpha-3
• Gene Name: ATP1A3
• Related Disease:
  Alternating hemiplegia of childhood 2
  ATP1A3-associated neurological disorder
  Auditory neuropathy
  Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
  Cognitive impairment
  Nervous system disease
  Adult glioblastoma
  Alternating hemiplegia
  Alternating hemiplegia of childhood 1
  Autosomal recessive juvenile Parkinson disease 2
  Autosomal recessive Parkinson disease 14
  Cardiac arrest
  Cardiac failure
  Cerebellar disorder
  Congestive heart failure
  Depression
  Developmental and epileptic encephalopathy 99
  Dystonia
  Dystonia 12
  Epilepsy
  Glioblastoma multiforme
  Glioma
  Hand, foot and mouth disease
  Hemiplegia
  Infantile epileptic-dyskinetic encephalopathy
  Juvenile-onset Parkinson disease
  Myoclonic dystonia 11
  Myotonic dystrophy
  Neoplasm
  Neurodevelopmental disorder
  Pancreatic adenocarcinoma
  Parkinson disease
  Paroxysmal dystonia
  Proliferative diabetic retinopathy
  Sensorineural hearing loss disorder
  X-linked reticulate pigmentary disorder
  Cerebellar ataxia
  Encephalopathy, acute, infection-induced
  Isolated congenital microcephaly
  Movement disorder
  X-linked adrenal hypoplasia congenita
  Alternating hemiplegia of childhood
  Migraine, familial hemiplegic, 2
  Osteoarthritis
  Parkinsonian disorder
• UniProt ID: AT1A3_HUMAN
• PDB ID: 8D3U; 8D3V; 8D3W; 8D3X; 8D3Y
• EC Number: 7.2.2.13
• Pfam ID: PF13246 ; PF00689 ; PF00690 ; PF00122
• Sequence:
  MGDKKDDKDSPKKNKGKERRDLDDLKKEVAMTEHKMSVEEVCRKYNTDCVQGLTHSKAQE
  ILARDGPNALTPPPTTPEWVKFCRQLFGGFSILLWIGAILCFLAYGIQAGTEDDPSGDNL
  YLGIVLAAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIREGEKMQVNAEEVVVGDL
  VEIKGGDRVPADLRIISAHGCKVDNSSLTGESEPQTRSPDCTHDNPLETRNITFFSTNCV
  EGTARGVVVATGDRTVMGRIATLASGLEVGKTPIAIEIEHFIQLITGVAVFLGVSFFILS
  LILGYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKNLEAVETLGST
  STICSDKTGTLTQNRMTVAHMWFDNQIHEADTTEDQSGTSFDKSSHTWVALSHIAGLCNR
  AVFKGGQDNIPVLKRDVAGDASESALLKCIELSSGSVKLMRERNKKVAEIPFNSTNKYQL
  SIHETEDPNDNRYLLVMKGAPERILDRCSTILLQGKEQPLDEEMKEAFQNAYLELGGLGE
  RVLGFCHYYLPEEQFPKGFAFDCDDVNFTTDNLCFVGLMSMIDPPRAAVPDAVGKCRSAG
  IKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDAKACVIHGTDL
  KDFTSEQIDEILQNHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVNDSPALKKADI
  GVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTLTSNIPEITPF
  LLFIMANIPLPLGTITILCIDLGTDMVPAISLAYEAAESDIMKRQPRNPRTDKLVNERLI
  SMAYGQIGMIQALGGFFSYFVILAENGFLPGNLVGIRLNWDDRTVNDLEDSYGQQWTYEQ
  RKVVEFTCHTAFFVSIVVVQWADLIICKTRRNSVFQQGMKNKILIFGLFEETALAAFLSY
  CPGMDVALRMYPLKPSWWFCAFPYSFLIFVYDEIRKLILRRNPGGWVEKETYY
• Function: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
• 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 transport by P-type ATPases (R-HSA-936837)
  Potential therapeutics for SARS (R-HSA-9679191)
  Ion homeostasis (R-HSA-5578775)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alternating hemiplegia of childhood 2	DIS25FT5	Definitive	Autosomal dominant	[1]
ATP1A3-associated neurological disorder	DISRW48Z	Definitive	Autosomal dominant	[2]
Auditory neuropathy	DISM6GAU	Definitive	Genetic Variation	[3]
Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome	DIS6OVTM	Definitive	Autosomal dominant	[1]
Cognitive impairment	DISH2ERD	Definitive	Genetic Variation	[4]
Nervous system disease	DISJ7GGT	Definitive	Genetic Variation	[5]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[6]
Alternating hemiplegia	DIS25HMJ	Strong	Genetic Variation	[7]
Alternating hemiplegia of childhood 1	DISD5VAX	Strong	Autosomal dominant	[8]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Biomarker	[9]
Autosomal recessive Parkinson disease 14	DISYC4IP	Strong	Genetic Variation	[10]
Cardiac arrest	DIS9DIA4	Strong	Genetic Variation	[11]
Cardiac failure	DISDC067	Strong	Biomarker	[12]
Cerebellar disorder	DIS2O7WM	Strong	Genetic Variation	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Depression	DIS3XJ69	Strong	Biomarker	[14]
Developmental and epileptic encephalopathy 99	DISWOQQ0	Strong	Autosomal dominant	[15]
Dystonia	DISJLFGW	Strong	Genetic Variation	[4]
Dystonia 12	DISNX38R	Strong	Autosomal dominant	[16]
Epilepsy	DISBB28L	Strong	Genetic Variation	[5]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hand, foot and mouth disease	DISKJHLL	Strong	Biomarker	[18]
Hemiplegia	DISVVH6I	Strong	Genetic Variation	[4]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Biomarker	[19]
Juvenile-onset Parkinson disease	DISNT5BI	Strong	Biomarker	[9]
Myoclonic dystonia 11	DISMVAWP	Strong	Biomarker	[20]
Myotonic dystrophy	DISNBEMX	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Altered Expression	[22]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[23]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[24]
Parkinson disease	DISQVHKL	Strong	Biomarker	[25]
Paroxysmal dystonia	DISV0MSQ	Strong	Biomarker	[9]
Proliferative diabetic retinopathy	DISQZ13G	Strong	Biomarker	[26]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[27]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Biomarker	[26]
Cerebellar ataxia	DIS9IRAV	moderate	Genetic Variation	[28]
Encephalopathy, acute, infection-induced	DISRRNDL	Moderate	Autosomal dominant	[1]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[29]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[10]
X-linked adrenal hypoplasia congenita	DISNMXY8	moderate	Genetic Variation	[30]
Alternating hemiplegia of childhood	DISB31JE	Supportive	Autosomal dominant	[31]
Migraine, familial hemiplegic, 2	DISJPXBR	Limited	Biomarker	[32]
Osteoarthritis	DIS05URM	Limited	Biomarker	[33]
Parkinsonian disorder	DISHGY45	Limited	Genetic Variation	[34]

11 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 Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[37]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[38]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[39]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[44]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3).	[45]

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 alpha-3 (ATP1A3).	[42]

References

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