Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBG1FU4)

• DOT Name: Piezo-type mechanosensitive ion channel component 1 (PIEZO1)
• Synonyms: Membrane protein induced by beta-amyloid treatment; Mib; Protein FAM38A
• Gene Name: PIEZO1
• Related Disease:
  Behcet disease
  PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis
  Acute myocardial infarction
  Adult respiratory distress syndrome
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Autism spectrum disorder
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Chromosomal disorder
  Congestive heart failure
  Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema
  Glioblastoma multiforme
  Glioma
  Hennekam lymphangiectasia-lymphedema syndrome 1
  Lymphatic malformation 6
  Malaria
  Meningioma
  Myocardial infarction
  Non-immune hydrops fetalis
  Osteoarthritis
  Osteoporosis
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Small lymphocytic lymphoma
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Bacterial infection
  High blood pressure
  Krabbe disease
  Obesity
  Small-cell lung cancer
  Varicose veins
  Dehydrated hereditary stomatocytosis
  Adult glioblastoma
  Bone osteosarcoma
  Gastric cancer
  Hemolytic anemia
  Osteosarcoma
  Sickle-cell anaemia
  Stomach cancer
  Wilms tumor
• UniProt ID: PIEZ1_HUMAN
• Pfam ID: PF15917 ; PF12166
• Sequence:
  MEPHVLGAVLYWLLLPCALLAACLLRFSGLSLVYLLFLLLLPWFPGPTRCGLQGHTGRLL
  RALLGLSLLFLVAHLALQICLHIVPRLDQLLGPSCSRWETLSRHIGVTRLDLKDIPNAIR
  LVAPDLGILVVSSVCLGICGRLARNTRQSPHPRELDDDERDVDASPTAGLQEAATLAPTR
  RSRLAARFRVTAHWLLVAAGRVLAVTLLALAGIAHPSALSSVYLLLFLALCTWWACHFPI
  STRGFSRLCVAVGCFGAGHLICLYCYQMPLAQALLPPAGIWARVLGLKDFVGPTNCSSPH
  ALVLNTGLDWPVYASPGVLLLLCYATASLRKLRAYRPSGQRKEAAKGYEARELELAELDQ
  WPQERESDQHVVPTAPDTEADNCIVHELTGQSSVLRRPVRPKRAEPREASPLHSLGHLIM
  DQSYVCALIAMMVWSITYHSWLTFVLLLWACLIWTVRSRHQLAMLCSPCILLYGMTLCCL
  RYVWAMDLRPELPTTLGPVSLRQLGLEHTRYPCLDLGAMLLYTLTFWLLLRQFVKEKLLK
  WAESPAALTEVTVADTEPTRTQTLLQSLGELVKGVYAKYWIYVCAGMFIVVSFAGRLVVY
  KIVYMFLFLLCLTLFQVYYSLWRKLLKAFWWLVVAYTMLVLIAVYTFQFQDFPAYWRNLT
  GFTDEQLGDLGLEQFSVSELFSSILVPGFFLLACILQLHYFHRPFMQLTDMEHVSLPGTR
  LPRWAHRQDAVSGTPLLREEQQEHQQQQQEEEEEEEDSRDEGLGVATPHQATQVPEGAAK
  WGLVAERLLELAAGFSDVLSRVQVFLRRLLELHVFKLVALYTVWVALKEVSVMNLLLVVL
  WAFALPYPRFRPMASCLSTVWTCVIIVCKMLYQLKVVNPQEYSSNCTEPFPNSTNLLPTE
  ISQSLLYRGPVDPANWFGVRKGFPNLGYIQNHLQVLLLLVFEAIVYRRQEHYRRQHQLAP
  LPAQAVFASGTRQQLDQDLLGCLKYFINFFFYKFGLEICFLMAVNVIGQRMNFLVTLHGC
  WLVAILTRRHRQAIARLWPNYCLFLALFLLYQYLLCLGMPPALCIDYPWRWSRAVPMNSA
  LIKWLYLPDFFRAPNSTNLISDFLLLLCASQQWQVFSAERTEEWQRMAGVNTDRLEPLRG
  EPNPVPNFIHCRSYLDMLKVAVFRYLFWLVLVVVFVTGATRISIFGLGYLLACFYLLLFG
  TALLQRDTRARLVLWDCLILYNVTVIISKNMLSLLACVFVEQMQTGFCWVIQLFSLVCTV
  KGYYDPKEMMDRDQDCLLPVEEAGIIWDSVCFFFLLLQRRVFLSHYYLHVRADLQATALL
  ASRGFALYNAANLKSIDFHRRIEEKSLAQLKRQMERIRAKQEKHRQGRVDRSRPQDTLGP
  KDPGLEPGPDSPGGSSPPRRQWWRPWLDHATVIHSGDYFLFESDSEEEEEAVPEDPRPSA
  QSAFQLAYQAWVTNAQAVLRRRQQEQEQARQEQAGQLPTGGGPSQEVEPAEGPEEAAAGR
  SHVVQRVLSTAQFLWMLGQALVDELTRWLQEFTRHHGTMSDVLRAERYLLTQELLQGGEV
  HRGVLDQLYTSQAEATLPGPTEAPNAPSTVSSGLGAEEPLSSMTDDMGSPLSTGYHTRSG
  SEEAVTDPGEREAGASLYQGLMRTASELLLDRRLRIPELEEAELFAEGQGRALRLLRAVY
  QCVAAHSELLCYFIIILNHMVTASAGSLVLPVLVFLWAMLSIPRPSKRFWMTAIVFTEIA
  VVVKYLFQFGFFPWNSHVVLRRYENKPYFPPRILGLEKTDGYIKYDLVQLMALFFHRSQL
  LCYGLWDHEEDSPSKEHDKSGEEEQGAEEGPGVPAATTEDHIQVEARVGPTDGTPEPQVE
  LRPRDTRRISLRFRRRKKEGPARKGAAAIEAEDREEEEGEEEKEAPTGREKRPSRSGGRV
  RAAGRRLQGFCLSLAQGTYRPLRRFFHDILHTKYRAATDVYALMFLADVVDFIIIIFGFW
  AFGKHSAATDITSSLSDDQVPEAFLVMLLIQFSTMVVDRALYLRKTVLGKLAFQVALVLA
  IHLWMFFILPAVTERMFNQNVVAQLWYFVKCIYFALSAYQIRCGYPTRILGNFLTKKYNH
  LNLFLFQGFRLVPFLVELRAVMDWVWTDTTLSLSSWMCVEDIYANIFIIKCSRETEKKYP
  QPKGQKKKKIVKYGMGGLIILFLIAIIWFPLLFMSLVRSVVGVVNQPIDVTVTLKLGGYE
  PLFTMSAQQPSIIPFTAQAYEELSRQFDPQPLAMQFISQYSPEDIVTAQIEGSSGALWRI
  SPPSRAQMKRELYNGTADITLRFTWNFQRDLAKGGTVEYANEKHMLALAPNSTARRQLAS
  LLEGTSDQSVVIPNLFPKYIRAPNGPEANPVKQLQPNEEADYLGVRIQLRREQGAGATGF
  LEWWVIELQECRTDCNLLPMVIFSDKVSPPSLGFLAGYGIMGLYVSIVLVIGKFVRGFFS
  EISHSIMFEELPCVDRILKLCQDIFLVRETRELELEEELYAKLIFLYRSPETMIKWTREK
  E
• Function: Pore-forming subunit of a mechanosensitive non-specific cation channel. Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents. Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation. Plays a key role in blood vessel formation and vascular structure in both development and adult physiology. Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation.
• Tissue Specificity: Expressed in numerous tissues. In normal brain, expressed exclusively in neurons, not in astrocytes. In Alzheimer disease brains, expressed in about half of the activated astrocytes located around classical senile plaques. In Parkinson disease substantia nigra, not detected in melanin-containing neurons nor in activated astrocytes. Expressed in erythrocytes (at protein level). Expressed in myoblasts (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Definitive	Genetic Variation	[1]
PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis	DISXXP9R	Definitive	Autosomal recessive	[2]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[3]
Adult respiratory distress syndrome	DISIJV47	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Astrocytoma	DISL3V18	Strong	Genetic Variation	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[9]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cardiac failure	DISDC067	Strong	Altered Expression	[11]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[12]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[11]
Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema	DIS4WDHV	Strong	Autosomal dominant	[2]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Biomarker	[14]
Hennekam lymphangiectasia-lymphedema syndrome 1	DISB203L	Strong	Genetic Variation	[15]
Lymphatic malformation 6	DISXFK12	Strong	Autosomal recessive	[16]
Malaria	DISQ9Y50	Strong	Genetic Variation	[17]
Meningioma	DISPT4TG	Strong	Biomarker	[12]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[11]
Non-immune hydrops fetalis	DISPUY8C	Strong	Genetic Variation	[15]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[18]
Osteoporosis	DISF2JE0	Strong	Biomarker	[19]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[22]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[24]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[25]
High blood pressure	DISY2OHH	moderate	Biomarker	[26]
Krabbe disease	DIS6H1IB	moderate	Genetic Variation	[27]
Obesity	DIS47Y1K	moderate	Biomarker	[28]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[29]
Varicose veins	DISIMBN2	moderate	Genetic Variation	[30]
Dehydrated hereditary stomatocytosis	DISGQT6H	Supportive	Autosomal dominant	[31]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[13]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[32]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[33]
Hemolytic anemia	DIS803XQ	Limited	Genetic Variation	[24]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[32]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[34]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[33]
Wilms tumor	DISB6T16	Limited	Altered Expression	[35]

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 Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[41]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[42]
Selenium	DM25CGV	Approved	Selenium increases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[43]
Cerulenin	DM6N4PR	Approved	Cerulenin affects the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[45]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[48]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[50]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of Piezo-type mechanosensitive ion channel component 1 (PIEZO1).	[45]

References

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• [15] Author Correction: Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.Nat Commun. 2019 Apr 26;10(1):1951. doi: 10.1038/s41467-019-09905-4.
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