E2JF22
uniprot
E2JF22
canonical
activity_regulation
ACTIVITY REGULATION: Regulated by auxillary subunits MDFIC and MDFI (PubMed:37590348). Down-regulated by phosphatidylserines exposed on the cell surface (PubMed:29799007). Divalent ions decrease the single-channel permeability of K(+) (By similarity). {ECO:0000250|UniProtKB:Q92508, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:37590348}.
uniprot
proteins
amino_acid_sequence
MEPHVLGAGLYWLLLPCTLLAASLLRFNALSLVYLLFLLLLPWLPGPSRHSIPGHTGRLLRALLCLSLLFLVAHLAFQICLHTVPHLDQFLGQNGSLWVKVSQHIGVTRLDLKDIFNTTRLVAPDLGVLLASSLCLGLCGRLTRKAGQSRRTQELQDDDDDDDDDDEDIDAAPAVGLKGAPALATKRRLWLASRFRVTAHWLLMTSGRTLVIVLLALAGIAHPSAFSSIYLVVFLAICTWWSCHFPLSPLGFNTLCVMVSCFGAGHLICLYCYQTPFIQDMLPPGNIWARLFGLKNFVDLPNYSSPNALVLNTKHAWPIYVSPGILLLLYYTATSLLKLHKSCPSELRKETPREDEEHELELDHLEPEPQARDATQGEMPMTTEPDLDNCTVHVLTSQSPVRQRPVRPRLAELKEMSPLHGLGHLIMDQSYVCALIAMMVWSIMYHSWLTFVLLLWACLIWTVRSRHQLAMLCSPCILLYGLTLCCLRYVWAMELPELPTTLGPVSLHQLGLEHTRYPCLDLGAMLLYLLTFWLLLRQFVKEKLLKKQKVPAALLEVTVADTEPTQTQTLLRSLGELVTGIYVKYWIYVCAGMFIVVSFAGRLVVYKIVYMFLFLLCLTLFQVYYTLWRKLLRVFWWLVVAYTMLVLIAVYTFQFQDFPTYWRNLTGFTDEQLGDLGLEQFSVSELFSSILIPGFFLLACILQLHYFHRPFMQLTDLEHVPPPGTRHPRWAHRQDAVSEAPLLEHQEEEEVFREDGQSMDGPHQATQVPEGTASKWGLVADRLLDLAASFSAVLTRIQVFVRRLLELHVFKLVALYTVWVALKEVSVMNLLLVVLWAFALPYPRFRPMASCLSTVWTCIIIVCKMLYQLKIVNPHEYSSNCTEPFPNNTNLQPLEINQSLLYRGPVDPANWFGVRKGYPNLGYIQNHLQILLLLVFEAVVYRRQEHYRRQHQQAPLPAQAVCADGTRQRLDQDLLSCLKYFINFFFYKFGLEICFLMAVNVIGQRMNFMVILHGCWLVAILTRRRREAIARLWPNYCLFLTLFLLYQYLLCLGMPPALCIDYPWRWSKAIPMNSALIKWLYLPDFFRAPNSTNLISDFLLLLCASQQWQVFSAERTEEWQRMAGINTDHLEPLRGEPNPIPNFIHCRSYLDMLKVAVFRYLFWLVLVVVFVAGATRISIFGLGYLLACFYLLLFGTTLLQKDTRAQLVLWDCLILYNVTVIISKNMLSLLSCVFVEQMQSNFCWVIQLFSLVCTVKGYYDPKEMMTRDRDCLLPVEEAGIIWDSICFFFLLLQRRIFLSHYFLHVSADLKATALQASRGFALYNAANLKSINFHRQIEEKSLAQLKRQMKRIRAKQEKYRQSQASRGQLQSKDPQDPSQEPGPDSPGGSSPPRRQWWRPWLDHATVIHSGDYFLFESDSEEEEEALPEDPRPAAQSAFQMAYQAWVTNAQTVLRQRRERARQERAEQLASGGDLNPDVEPVDVPEDEMAGRSHMMQRVLSTMQFLWVLGQATVDGLTRWLRAFTKHHRTMSDVLCAERYLLTQELLRVGEVRRGVLDQLYVGEDEATLSGPVETRDGPSTASSGLGAEEPLSSMTDDTSSPLSTGYNTRSGSEEIVTDAGDLQAGTSLHGSQELLANARTRMRTASELLLDRRLHIPELEEAERFEAQQGRTLRLLRAGYQCVAAHSELLCYFIIILNHMVTASAASLVLPVLVFLWAMLTIPRPSKRFWMTAIVFTEVMVVTKYLFQFGFFPWNSYVVLRRYENKPYFPPRILGLEKTDSYIKYDLVQLMALFFHRSQLLCYGLWDHEEDRYPKDHCRSSVKDREAKEEPEAKLESQSETGTGHPKEPVLAGTPRDHIQGKGSIRSKDVIQDPPEDLKPRHTRHISIRFRRRKETPGPKGTAVMETEHEEGEGKETTERKRPRHTQEKSKFRERMKAAGRRLQSFCVSLAQSFYQPLQRFFHDILHTKYRAATDVYALMFLADIVDIIIIIFGFWAFGKHSAATDIASSLSDDQVPQAFLFMLLVQFGTMVIDRALYLRKTVLGKLAFQVVLVVAIHIWMFFILPAVTERMFSQNAVAQLWYFVKCIYFALSAYQIRCGYPTRILGNFLTKKYNHLNLFLFQGFRLVPFLVELRAVMDWVWTDTTLSLSNWMCVEDIYANIFIIKCSRETEKKYPQPKGQKKKKIVKYGMGGLIILFLIAIIWFPLLFMSLIRSVVGVVNQPIDVTVTLKLGGYEPLFTMSAQQPSIVPFTPQAYEELSQQFDPYPLAMQFISQYSPEDIVTAQIEGSSGALWRISPPSRAQMKQELYNGTADITLRFTWNFQRDLAKGGTVEYTNEKHTLELAPNSTARRQLAQLLEGRPDQSVVIPHLFPKYIRAPNGPEANPVKQLQPDEEEDYLGVRIQLRREQVGTGASGEQAGTKASDFLEWWVIELQDCKADCNLLPMVIFSDKVSPPSLGFLAGYGIVGLYVSIVLVVGKFVRGFFSEISHSIMFEELPCVDRILKLCQDIFLVRETRELELEEELYAKLIFLYRSPETMIKWTRERE
uniprot
proteins
function
FUNCTION: Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:20813920, PubMed:22343900, PubMed:38184690, PubMed:26390154, PubMed:29261642, PubMed:35388220, PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:26390154, PubMed:29261642, PubMed:35388220, PubMed:37590348). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium (PubMed:20813920, PubMed:22343900, PubMed:38228630). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+) (By similarity). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (By similarity). 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 (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (PubMed:38228630). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing (PubMed:24157948). Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (By similarity). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (PubMed:24958852, PubMed:25119035, PubMed:36515266). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells (PubMed:29799007). In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca(2+) influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). {ECO:0000250|UniProtKB:Q92508, ECO:0000269|PubMed:20813920, ECO:0000269|PubMed:22343900, ECO:0000269|PubMed:24157948, ECO:0000269|PubMed:24958852, ECO:0000269|PubMed:25119035, ECO:0000269|PubMed:26390154, ECO:0000269|PubMed:29261642, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:36515266, ECO:0000269|PubMed:37590348, ECO:0000269|PubMed:38184690, ECO:0000269|PubMed:38228630}.
uniprot
proteins
mass_dalton
292002
uniprot
proteins
mutagenesis
MUTAGEN 260; /note="S->R: Affects channel gating properties resulting in reduced pressure-induced channel opening. No effect on channel conductance. No effect on localization to cell membrane."; /evidence="ECO:0000269|PubMed:38184690"; MUTAGEN 2211; /note="S->L: Affects channel gating properties resulting in reduced pressure-induced channel opening. No effect on channel conductance. No effect on localization to cell membrane."; /evidence="ECO:0000269|PubMed:38184690"; MUTAGEN 2493..2496; /note="MFEE->AAAA: Hearing and vestibular impairment in conditional knockin mice in inner ear hair cells."; /evidence="ECO:0000269|PubMed:38228630"; MUTAGEN 2493..2494; /note="MF->AA: Non-functional channel. Proper trimeric assembly and subcellular location."; /evidence="ECO:0000269|PubMed:29261642"; MUTAGEN 2494; /note="F->A: Increased channel activity."; /evidence="ECO:0000269|PubMed:29261642
uniprot
proteins
protein_family
PIEZO (TC 1.A.75) family
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
20813920
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22343900
uniprot
proteins
pubmed
23479567
uniprot
proteins
pubmed
24157948
uniprot
proteins
pubmed
24662763
uniprot
proteins
pubmed
24958852
uniprot
proteins
pubmed
25119035
uniprot
proteins
pubmed
26390154
uniprot
proteins
pubmed
29261642
uniprot
proteins
pubmed
29799007
uniprot
proteins
pubmed
35388220
uniprot
proteins
pubmed
36515266
uniprot
proteins
pubmed
37590348
uniprot
proteins
pubmed
38184690
uniprot
proteins
pubmed
38228630
uniprot
proteins
sequence_length
2547
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q92508}; Multi-pass membrane protein {ECO:0000269|PubMed:29261642, ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348}. Endoplasmic reticulum-Golgi intermediate compartment membrane {ECO:0000250|UniProtKB:Q0KL00}. Cell membrane {ECO:0000269|PubMed:20813920, ECO:0000269|PubMed:26390154, ECO:0000269|PubMed:29261642, ECO:0000269|PubMed:36515266, ECO:0000269|PubMed:38184690, ECO:0000269|PubMed:38228630}; Multi-pass membrane protein {ECO:0000269|PubMed:26390154, ECO:0000269|PubMed:29261642, ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348}. Cell projection, lamellipodium membrane {ECO:0000250|UniProtKB:Q92508}. Note=In erythrocytes, located in the plasma membrane (PubMed:23479567). Accumulates at the leading apical lamellipodia of endothelial cells in response to shear stress (By similarity). Colocalizes with F-actin and MYH9 at the actomyosin cortex in myoblasts. Non-uniform distribution of Piezo1 in the red blood cell membrane with an enrichment at the dimple (PubMed:36515266). Located at the tips and sides of stereocilia and cuticular plate membranes (PubMed:38228630). {ECO:0000250|UniProtKB:Q92508, ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:29799007, ECO:0000269|PubMed:36515266, ECO:0000269|PubMed:38228630}.
uniprot
proteins
transmembrane_region
TRANSMEM 13..25; /note="Helical; Name=1"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 29..44; /note="Helical; Name=2"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 59..81; /note="Helical; Name=3"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 122..138; /note="Helical; Name=4"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 202..221; /note="Helical; Name=5"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 224..243; /note="Helical; Name=6"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 255..275; /note="Helical; Name=7"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 317..337; /note="Helical; Name=8"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 425..445; /note="Helical; Name=9"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 448..463; /note="Helical; Name=10"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 469..491; /note="Helical; Name=11"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 519..536; /note="Helical; Name=12"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 581..601; /note="Helical; Name=13"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 603..623; /note="Helical; Name=14"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 634..655; /note="Helical; Name=15"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 686..702; /note="Helical; Name=16"; /evidence="ECO:0000305|PubMed:35388220, ECO:0000305|PubMed:37590348"; TRANSMEM 812..823; /note="Helical; Name=17"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 827..840; /note="Helical; Name=18"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 855..869; /note="Helical; Name=19"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 922..949; /note="Helical; Name=20"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 990..1005; /note="Helical; Name=21"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1008..1023; /note="Helical; Name=22"; /evidence="ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1037..1052; /note="Helical; Name=23"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1092..1113; /note="Helical; Name=24"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1149..1175; /note="Helical; Name=25"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1181..1199; /note="Helical; Name=26"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1213..1231; /note="Helical; Name=27"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1281..1297; /note="Helical; Name=28"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1657..1700; /note="Helical; Name=29"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1705..1720; /note="Helical; Name=30"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1729..1747; /note="Helical; Name=31"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1780..1801; /note="Helical; Name=32"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 1977..1996; /note="Helical; Name=33"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 2017..2033; /note="Helical; Name=34"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 2048..2068; /note="Helical; Name=35"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 2077..2092; /note="Helical; Name=36"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 2193..2213; /note="Helical; Name=37"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ"; TRANSMEM 2458..2478; /note="Helical; Name=38"; /evidence="ECO:0000269|PubMed:35388220, ECO:0000269|PubMed:37590348, ECO:0007744|PDB:7WLT, ECO:0007744|PDB:8IMZ
uniprot
proteins