Details of Drug Off-Target (DOT)

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

• DOT Name: Plasma membrane calcium-transporting ATPase 4 (ATP2B4)
• Synonyms: PMCA4; EC 7.2.2.10; Matrix-remodeling-associated protein 1; Plasma membrane calcium ATPase isoform 4; Plasma membrane calcium pump isoform 4
• Gene Name: ATP2B4
• Related Disease:
  Alzheimer disease
  Androgen insensitivity syndrome
  Cardiac failure
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Dystonia
  Familial long QT syndrome
  High blood pressure
  Invasive breast carcinoma
  Male infertility
  Neoplasm
  Schizophrenia
  Advanced cancer
  Leishmaniasis
  Breast cancer
  Breast carcinoma
  Cutaneous melanoma
  Melanoma
  Neuroblastoma
  Sickle-cell anaemia
  Small lymphocytic lymphoma
• UniProt ID: AT2B4_HUMAN
• PDB ID: 1CFF; 2KNE
• EC Number: 7.2.2.10
• Pfam ID: PF12424 ; PF13246 ; PF00689 ; PF00690 ; PF00122 ; PF00702
• Sequence:
  MTNPSDRVLPANSMAESREGDFGCTVMELRKLMELRSRDALTQINVHYGGVQNLCSRLKT
  SPVEGLSGNPADLEKRRQVFGHNVIPPKKPKTFLELVWEALQDVTLIILEIAAIISLVLS
  FYRPAGEENELCGQVATTPEDENEAQAGWIEGAAILFSVIIVVLVTAFNDWSKEKQFRGL
  QCRIEQEQKFSIIRNGQLIQLPVAEIVVGDIAQVKYGDLLPADGILIQGNDLKIDESSLT
  GESDHVKKSLDKDPMLLSGTHVMEGSGRMVVTAVGVNSQTGIILTLLGVNEDDEGEKKKK
  GKKQGVPENRNKAKTQDGVALEIQPLNSQEGIDNEEKDKKAVKVPKKEKSVLQGKLTRLA
  VQIGKAGLLMSALTVFILILYFVIDNFVINRRPWLPECTPIYIQYFVKFFIIGITVLVVA
  VPEGLPLAVTISLAYSVKKMMKDNNLVRHLDACETMGNATAICSDKTGTLTMNRMTVVQA
  YIGGIHYRQIPSPDVFLPKVLDLIVNGISINSAYTSKILPPEKEGGLPRQVGNKTECALL
  GFVTDLKQDYQAVRNEVPEEKLYKVYTFNSVRKSMSTVIRNPNGGFRMYSKGASEIILRK
  CNRILDRKGEAVPFKNKDRDDMVRTVIEPMACDGLRTICIAYRDFDDTEPSWDNENEILT
  ELTCIAVVGIEDPVRPEVPDAIAKCKQAGITVRMVTGDNINTARAIATKCGILTPGDDFL
  CLEGKEFNRLIRNEKGEVEQEKLDKIWPKLRVLARSSPTDKHTLVKGIIDSTVGEHRQVV
  AVTGDGTNDGPALKKADVGFAMGIAGTDVAKEASDIILTDDNFTSIVKAVMWGRNVYDSI
  SKFLQFQLTVNVVAVIVAFTGACITQDSPLKAVQMLWVNLIMDTFASLALATEPPTESLL
  KRRPYGRNKPLISRTMMKNILGHAFYQLIVIFILVFAGEKFFDIDSGRKAPLHSPPSQHY
  TIVFNTFVLMQLFNEINSRKIHGEKNVFSGIYRNIIFCSVVLGTFICQIFIVEFGGKPFS
  CTSLSLSQWLWCLFIGIGELLWGQFISAIPTRSLKFLKEAGHGTTKEEITKDAEGLDEID
  HAEMELRRGQILWFRGLNRIQTQIDVINTFQTGASFKGVLRRQNMGQHLDVKLVPSSSYI
  KVVKAFHSSLHESIQKPYNQKSIHSFMTHPEFAIEEELPRTPLLDEEEEENPDKASKFGT
  RVLLLDGEVTPYANTNNNAVDCNQVQLPQSDSSLQSLETSV
• Function: Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell. By regulating sperm cell calcium homeostasis, may play a role in sperm motility.
• Tissue Specificity: Isoform XB is the most abundant isoform and is expressed ubiquitously. Isoforms containing segment Z have only been detected in heart, while isoforms containing segment a have been found in heart, stomach and brain cortex.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  cAMP sig.ling pathway (hsa04024)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Aldosterone synthesis and secretion (hsa04925)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Salivary secretion (hsa04970)
  Pancreatic secretion (hsa04972)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Ion homeostasis (R-HSA-5578775)
  Ion transport by P-type ATPases (R-HSA-936837)
  Reduction of cytosolic Ca++ levels (R-HSA-418359)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Androgen insensitivity syndrome	DISUZBBO	Strong	Altered Expression	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Altered Expression	[4]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Dystonia	DISJLFGW	Strong	Biomarker	[6]
Familial long QT syndrome	DISRNNCY	Strong	Genetic Variation	[7]
High blood pressure	DISY2OHH	Strong	Biomarker	[8]
Invasive breast carcinoma	DISANYTW	Strong	Altered Expression	[9]
Male infertility	DISY3YZZ	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[11]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[12]
Leishmaniasis	DISABTW7	Disputed	Biomarker	[13]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[9]
Cutaneous melanoma	DIS3MMH9	Limited	Altered Expression	[14]
Melanoma	DIS1RRCY	Limited	Altered Expression	[14]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[15]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[16]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[17]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Plasma membrane calcium-transporting ATPase 4 (ATP2B4) decreases the response to substance of Irinotecan.	[40]
Phenylephrine	DMZHUO5	Approved	Plasma membrane calcium-transporting ATPase 4 (ATP2B4) increases the response to substance of Phenylephrine.	[41]
PGF2alpha	DM4XAU7	Clinical trial	Plasma membrane calcium-transporting ATPase 4 (ATP2B4) increases the response to substance of PGF2alpha.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[18]

24 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 Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[21]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[22]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[24]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[25]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[22]
Marinol	DM70IK5	Approved	Marinol increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[26]
Selenium	DM25CGV	Approved	Selenium increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[27]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[28]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[30]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[31]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[32]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[32]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Plasma membrane calcium-transporting ATPase 4 (ATP2B4).	[39]

References

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