Details of Drug Off-Target (DOT)

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

• DOT Name: Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3)
• Synonyms: SERCA3; SR Ca(2+)-ATPase 3; EC 7.2.2.10; Calcium pump 3
• Gene Name: ATP2A3
• Related Disease:
  Colorectal adenoma
  Colorectal carcinoma
  Metastatic sarcoma
  Non-insulin dependent diabetes
  Adenocarcinoma
  Adenoma
  Advanced cancer
  Atrial fibrillation
  Barrett esophagus
  Breast cancer
  Burkitt lymphoma
  Cardiac failure
  Chagas disease
  Chronic kidney disease
  Colon cancer
  Congestive heart failure
  Darier disease
  Familial adenomatous polyposis
  Gastroesophageal reflux disease
  Head-neck squamous cell carcinoma
  Leukemia
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell neoplasm
  Breast carcinoma
  Carcinoma
  Colon carcinoma
  Colonic neoplasm
  Hepatocellular carcinoma
  Obesity
  Leishmaniasis
  Asthma
  High blood pressure
  Hyperglycemia
  Lung cancer
  Lung carcinoma
  Sphingolipidosis
  Squamous cell carcinoma
• UniProt ID: AT2A3_HUMAN
• EC Number: 7.2.2.10
• Pfam ID: PF13246 ; PF00689 ; PF00690 ; PF00122 ; PF00702
• Sequence:
  MEAAHLLPAADVLRHFSVTAEGGLSPAQVTGARERYGPNELPSEEGKSLWELVLEQFEDL
  LVRILLLAALVSFVLAWFEEGEETTTAFVEPLVIMLILVANAIVGVWQERNAESAIEALK
  EYEPEMGKVIRSDRKGVQRIRARDIVPGDIVEVAVGDKVPADLRLIEIKSTTLRVDQSIL
  TGESVSVTKHTEAIPDPRAVNQDKKNMLFSGTNITSGKAVGVAVATGLHTELGKIRSQMA
  AVEPERTPLQRKLDEFGRQLSHAISVICVAVWVINIGHFADPAHGGSWLRGAVYYFKIAV
  ALAVAAIPEGLPAVITTCLALGTRRMARKNAIVRSLPSVETLGCTSVICSDKTGTLTTNQ
  MSVCRMFVVAEADAGSCLLHEFTISGTTYTPEGEVRQGDQPVRCGQFDGLVELATICALC
  NDSALDYNEAKGVYEKVGEATETALTCLVEKMNVFDTDLQALSRVERAGACNTVIKQLMR
  KEFTLEFSRDRKSMSVYCTPTRPHPTGQGSKMFVKGAPESVIERCSSVRVGSRTAPLTPT
  SREQILAKIRDWGSGSDTLRCLALATRDAPPRKEDMELDDCSKFVQYETDLTFVGCVGML
  DPPRPEVAACITRCYQAGIRVVMITGDNKGTAVAICRRLGIFGDTEDVAGKAYTGREFDD
  LSPEQQRQACRTARCFARVEPAHKSRIVENLQSFNEITAMTGDGVNDAPALKKAEIGIAM
  GSGTAVAKSAAEMVLSDDNFASIVAAVEEGRAIYSNMKQFIRYLISSNVGEVVCIFLTAI
  LGLPEALIPVQLLWVNLVTDGLPATALGFNPPDLDIMEKLPRSPREALISGWLFFRYLAI
  GVYVGLATVAAATWWFVYDAEGPHINFYQLRNFLKCSEDNPLFAGIDCEVFESRFPTTMA
  LSVLVTIEMCNALNSVSENQSLLRMPPWMNPWLLVAVAMSMALHFLILLVPPLPLIFQVT
  PLSGRQWVVVLQISLPVILLDEALKYLSRNHMHEEMSQK
• Function: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
• Tissue Specificity: Found in most tissues. Most abundant in thymus, trachea, salivary gland, spleen, bone marrow, lymph node, peripheral leukocytes, pancreas and colon. Also detected in fetal tissues. Expressed in cell lineages of hematopoietic, epithelial, or embryonic origin and also expressed in several cancer cell lines.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Efferocytosis (hsa04148)
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Osteoclast differentiation (hsa04380)
  Thyroid hormone sig.ling pathway (hsa04919)
  Pancreatic secretion (hsa04972)
  Alzheimer disease (hsa05010)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Reduction of cytosolic Ca++ levels (R-HSA-418359)
  Ion homeostasis (R-HSA-5578775)
  Ion transport by P-type ATPases (R-HSA-936837)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal adenoma	DISTSVHM	Definitive	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Metastatic sarcoma	DISKYC7V	Definitive	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[3]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Chagas disease	DIS8KNVF	Strong	Biomarker	[8]
Chronic kidney disease	DISW82R7	Strong	Altered Expression	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Darier disease	DIS4WI7S	Strong	Biomarker	[11]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[12]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Altered Expression	[14]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[16]
Squamous cell neoplasm	DISKBRLI	Strong	Genetic Variation	[17]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[5]
Carcinoma	DISH9F1N	moderate	Altered Expression	[18]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[10]
Colonic neoplasm	DISSZ04P	moderate	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[19]
Obesity	DIS47Y1K	moderate	Biomarker	[20]
Leishmaniasis	DISABTW7	Disputed	Biomarker	[21]
Asthma	DISW9QNS	Limited	Biomarker	[22]
High blood pressure	DISY2OHH	Limited	Biomarker	[23]
Hyperglycemia	DIS0BZB5	Limited	Genetic Variation	[24]
Lung cancer	DISCM4YA	Limited	Altered Expression	[25]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[25]
Sphingolipidosis	DISEC08E	Limited	Biomarker	[26]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[17]

5 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 Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[27]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[31]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[34]

13 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 Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[32]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[33]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[35]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[36]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[37]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[40]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[41]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (ATP2A3).	[42]

References

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