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Piezo1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2945

Nomenclature: Piezo1

Family: Piezo channels

Annotation status:  image of a red circle Awaiting annotation  » Email us

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 36 2521 16q24.3 PIEZO1 piezo type mechanosensitive ion channel component 1 (Er blood group)
Mouse 35 2547 8 E1 Piezo1 piezo-type mechanosensitive ion channel component 1
Rat 35 2535 19q12 Piezo1 piezo-type mechanosensitive ion channel component 1
Gene and Protein Information Comments
Piezo proteins have between 24 and 36 predicted transmembrane (TM) domains, although a much lower number (14) of TM domains are resolved in the Piezo1 structure than initially predicted through topology software [3].
Previous and Unofficial Names Click here for help
FAM38A | family with sequence similarity 38, member A | KIAA0233 | Mib | PIEZ1 | piezo type mechanosensitive ion channel component 1
Database Links Click here for help
Alphafold Q92508 (Hs), E2JF22 (Mm), Q0KL00 (Rn)
Ensembl Gene ENSG00000103335 (Hs), ENSMUSG00000014444 (Mm), ENSRNOG00000056786 (Rn)
Entrez Gene 9780 (Hs), 234839 (Mm), 361430 (Rn)
Human Protein Atlas ENSG00000103335 (Hs)
KEGG Gene hsa:9780 (Hs), mmu:234839 (Mm), rno:361430 (Rn)
OMIM 611184 (Hs)
Orphanet ORPHA303176 (Hs)
Pharos Q92508 (Hs)
RefSeq Nucleotide NM_001142864 (Hs), NM_001037298 (Mm), NM_001077200 (Rn)
RefSeq Protein NP_001136336 (Hs), NP_001032375 (Mm), NP_001070668 (Rn)
UniProtKB Q92508 (Hs), E2JF22 (Mm), Q0KL00 (Rn)
Wikipedia PIEZO1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM study of the mammalian mechanosensitive Piezo1 channel
PDB Id:  3JAC
Resolution:  4.8Å
Species:  Mouse
References:  5
Functional Characteristics Click here for help
Activation and deactivation, a few milliseconds; Inactivation, time constant 15 ms at -80 mV ranging to seconds or minutes and slower at positive voltages; Unitary conductance, 29 pS; Ion selectivity, monovalent and divalent cations (PCa/PCs 1.21) - Mouse (Mm).
Endogenous modulators (Human)
Cholesterol, 7-ketocholesterol, phosphatidylserine, phosphatidylinositol 4,5-bisphosphate, ceramide, docosahexaenoic acid, eicosapentaenoic acid, margaric acid, protons, amyloid beta (1-40) peptide
Physical activators (Human)
Membrane stretch, cell indentation, fluid shear stress, cell traction force, substrate stiffening

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Yoda2b Small molecule or natural product Mm Activation 6.9 pEC50 - no 9
⤷ pEC50 6.9 (EC50 1.26x10-7 M) [9]
Not voltage dependent
Yoda2 Small molecule or natural product Hs Activation 6.8 pEC50 - no 11
⤷ pEC50 6.8 (EC50 1.5x10-7 M) [11]
Not voltage dependent
Yaddle1 Small molecule or natural product Hs Activation 6.4 pEC50 - no 6
⤷ pEC50 6.4 (EC50 4x10-7 M) [6]
Not voltage dependent
Yoda1 Small molecule or natural product Mm Activation 4.8 pEC50 - no 13
⤷ pEC50 4.8 (EC50 1.71x10-5 M) [13]
Not voltage dependent
Yoda1 Small molecule or natural product Primary target of this compound Hs Activation 4.6 pEC50 - no 13
⤷ pEC50 4.6 (EC50 2.66x10-5 M) [13]
Not voltage dependent
Jedi2 Small molecule or natural product Primary target of this compound Mm Activation 3.8 pEC50 - no 14
⤷ pEC50 3.8 (EC50 1.58x10-4 M) [14]
Not voltage dependent
Description: Measuring calcium flux (GCAMP6s fluorescence) in mPiezo1-transfected HEK293T cells.
Jedi1 Small molecule or natural product Ligand has a PDB structure Mm Activation 3.8 pEC50 - no 14
⤷ pEC50 3.8 (EC50 1.6x10-4 M) [14]
Not voltage dependent
View species-specific activator tables
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
salvianolic acid B Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 - no 10
⤷ pIC50 5.9 [10]
Not voltage dependent
Dooku1 Small molecule or natural product Hs Inhibition 5.8 – 5.9 pIC50 - no 4
⤷ pIC50 5.9 (IC50 1.3x10-6 M) [4]
Not voltage dependent
Description: Measuring antagonism of Yoda1-mediated calcium entry in HEK293 cells exogenously expressing human Piezo1 channels.
pIC50 5.8 (IC50 1.5x10-6 M) [4]
Not voltage dependent
Description: Measuring antagonism of Yoda1-mediated calcium entry in HUVEC cells which endogenously express Piezo1 channels.
escin Small molecule or natural product Hs Inhibition 5.8 pIC50 - no 15
⤷ pIC50 5.8 [15]
Not voltage dependent
GsMTx-4 Peptide Click here for species-specific activity table Hs Inhibition 5.4 pIC50 - no 1
⤷ pIC50 5.4 [1]
Not voltage dependent
benzbromarone Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.4 pIC50 - no 7
⤷ pIC50 5.4 [7]
Not voltage dependent
Gd3+ Click here for species-specific activity table Hs Inhibition - - - no 2
⤷ @ 30 μM [2]
Not voltage dependent
ruthenium red Click here for species-specific activity table Hs Inhibition - - - no 2
⤷ @ 30 μM [2]
Not voltage dependent
propofol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition - - - no 18
⤷ @ 50 μM [18]
Not voltage dependent
Inhibitor Comments
The small molecule OB-1 disrupts self-association of the STOML3 Piezo channel modulator [16]. This mechanism reverses pathological mechanical hypersensitivity that is mediated by Piezo ion channels.
Immunopharmacology Comments
Work by Liu et al. (2018) shows that Piezo1 is involved in immune regulation [8]. Piezo1 signalling appears to cause a rearrangement of the actin scaffold, that connects this mechanosensor's function to optimal T cell receptor signalling and T cell activation. Knock out of Piezo1 channels in the innate immune cells of mice has shown that mechanosensation of force by Piezo1 in the lung is an essential component of innate immune system-mediated inflammatory reponses [12].
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  Piezo1 mechanosensors are involved in the optimisation of human T cell activation and in T cell proliferation.
References:  8
Tissue Distribution Click here for help
Cholinergic enteric neurons
Species:  Mouse
Technique:  real-time RT-qPCR, immunohistochemistry
References:  17
Physiological Functions Click here for help
Maintains mechanical and immunological homeostasis in the gastrointestinal (GI) tract by sensing force.
Species:  Mouse
Tissue: 
References:  17

References

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1. Bae C, Sachs F, Gottlieb PA. (2011) The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry, 50 (29): 6295-300. [PMID:21696149]

2. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science, 330 (6000): 55-60. [PMID:20813920]

3. Coste B, Murthy SE, Mathur J, Schmidt M, Mechioukhi Y, Delmas P, Patapoutian A. (2015) Piezo1 ion channel pore properties are dictated by C-terminal region. Nat Commun, 6: 7223. [PMID:26008989]

4. Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM, Hyman AJ, Hall SJ, Gaunt HJ, Ludlow MJ, Foster R et al.. (2018) Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br J Pharmacol, 175 (10): 1744-1759. [PMID:29498036]

5. Ge J, Li W, Zhao Q, Li N, Chen M, Zhi P, Li R, Gao N, Xiao B, Yang M. (2015) Architecture of the mammalian mechanosensitive Piezo1 channel. Nature, 527 (7576): 64-9. [PMID:26390154]

6. Goon S, Shiu Chen Liu C, Ghosh Dastidar U, Paul B, Mukherjee S, Sarkar HS, Desai M, Jana R, Pal S, Sreedevi NV et al.. (2024) Exploring the Structural Attributes of Yoda1 for the Development of New-Generation Piezo1 Agonist Yaddle1 as a Vaccine Adjuvant Targeting Optimal T Cell Activation. J Med Chem, 67 (10): 8225-8246. [PMID:38716967]

7. Liang P, Zhang Y, Wan YCS, Ma S, Dong P, Lowry AJ, Francis SJ, Khandelwal S, Delahunty M, Telen MJ et al.. (2024) Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis. Blood, 143 (4): 357-369. [PMID:38033286]

8. Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR, Rahaman O, Talukdar A, Ganguly D. (2018) Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation. J Immunol, 200 (4): 1255-1260. [PMID:29330322]

9. Ludlow MJ, Povstyan OV, Linley DM, Martin-Almedina S, Revill C, Cuthbertson K, Smith KA, Fay E, Fotiou E, Bush A et al.. (2025) PIEZO1 mechanical insensitivity in generalized lymphatic dysplasia with the potential for pharmacological rescue. iScience, Epun ahead of print. DOI: 10.1016/j.isci.2025.113110

10. Pan X, Wan R, Wang Y, Liu S, He Y, Deng B, Luo S, Chen Y, Wen L, Hong T et al.. (2022) Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B. Br J Pharmacol, 179 (14): 3778-3814. [PMID:35194776]

11. Parsonage G, Cuthbertson K, Endesh N, Murciano N, Hyman AJ, Revill CH, Povstyan OV, Chuntharpursat-Bon E, Debant M, Ludlow MJ et al.. (2023) Improved PIEZO1 agonism through 4-benzoic acid modification of Yoda1. Br J Pharmacol, 180 (16): 2039-2063. [PMID:36457143]

12. Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG et al.. (2019) Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature, 573 (7772): 69-74. [PMID:31435009]

13. Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, Lao J, Tully DC, Engels IH et al.. (2015) Chemical activation of the mechanotransduction channel Piezo1. Elife, 4. [PMID:26001275]

14. Wang Y, Chi S, Guo H, Li G, Wang L, Zhao Q, Rao Y, Zu L, He W, Xiao B. (2018) A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun, 9 (1): 1300. [PMID:29610524]

15. Wang Y, Chu T, Pan X, Bian Y, Li J. (2023) Escin ameliorates inflammation via inhibiting mechanical stretch and chemically induced Piezo1 activation in vascular endothelial cells. Eur J Pharmacol, 956: 175951. [PMID:37541373]

16. Wetzel C, Pifferi S, Picci C, Gök C, Hoffmann D, Bali KK, Lampe A, Lapatsina L, Fleischer R, Smith ES et al.. (2017) Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity. Nat Neurosci, 20 (2): 209-218. [PMID:27941788]

17. Xie Z, Rose L, Feng J, Zhao Y, Lu Y, Kane H, Hibberd TJ, Hu X, Wang Z, Zang K et al.. (2025) Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force. Cell, 188 (9): 2417-2432.e19. [PMID:40132579]

18. Yu D, Bae C. (2025) Propofol inhibits Piezo mechanosensitive channels. Biophys J, [Epub ahead of print]. [PMID:40485107]

How to cite this page

Piezo channels: Piezo1. Last modified on 21/07/2025. Accessed on 12/09/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2945.