1.A.75.1.14
Piezo1 (Fam38a) of 2547 aas and ~ 38 TMSs. The three-bladed propeller-like cryoEM structure and its mechanotransduction components are known (Zhao et al. 2018). There are nine repeat units consisting of four transmembrane helices, each of which is termed a transmembrane helical unit (THU). These assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90 Å-long intracellular beam-like structure, which undergoes a lever-like motion to connect the THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Thus, Piezo1 possesses a 38-transmembrane-helix topology with mechanotransduction components that enable a lever-like mechanogating mechanism (Zhao et al. 2018). The Piezo1 pore remains fully open if only one of the three subunits is activate, for example by binding the agonist, Yoda1 (Lacroix et al. 2018). Piezo1 mediates endothelial atherogenic inflammatory responses via regulation of YAP/TAZ activation (Yang et al. 2021). PIEZO1 mediates periostin+ myofibroblast activation and pulmonary fibrosis in mice (Xu et al. 2025).
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| Accession Number: | E2JF22 |
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| Protein Name: | Piezo-type mechanosensitive ion channel component 1 |
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| Length: | 2547 |
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| Molecular Weight: | 292002.00 |
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| Species: | Mus musculus (Mouse) [10090] |
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| Number of TMSs: | 39 |
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| Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
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| Substrate |
cation |
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1: MEPHVLGAGL YWLLLPCTLL AASLLRFNAL SLVYLLFLLL LPWLPGPSRH SIPGHTGRLL
61: RALLCLSLLF LVAHLAFQIC LHTVPHLDQF LGQNGSLWVK VSQHIGVTRL DLKDIFNTTR
121: LVAPDLGVLL ASSLCLGLCG RLTRKAGQSR RTQELQDDDD DDDDDDEDID AAPAVGLKGA
181: PALATKRRLW LASRFRVTAH WLLMTSGRTL VIVLLALAGI AHPSAFSSIY LVVFLAICTW
241: WSCHFPLSPL GFNTLCVMVS CFGAGHLICL YCYQTPFIQD MLPPGNIWAR LFGLKNFVDL
301: PNYSSPNALV LNTKHAWPIY VSPGILLLLY YTATSLLKLH KSCPSELRKE TPREDEEHEL
361: ELDHLEPEPQ ARDATQGEMP MTTEPDLDNC TVHVLTSQSP VRQRPVRPRL AELKEMSPLH
421: GLGHLIMDQS YVCALIAMMV WSIMYHSWLT FVLLLWACLI WTVRSRHQLA MLCSPCILLY
481: GLTLCCLRYV WAMELPELPT TLGPVSLHQL GLEHTRYPCL DLGAMLLYLL TFWLLLRQFV
541: KEKLLKKQKV PAALLEVTVA DTEPTQTQTL LRSLGELVTG IYVKYWIYVC AGMFIVVSFA
601: GRLVVYKIVY MFLFLLCLTL FQVYYTLWRK LLRVFWWLVV AYTMLVLIAV YTFQFQDFPT
661: YWRNLTGFTD EQLGDLGLEQ FSVSELFSSI LIPGFFLLAC ILQLHYFHRP FMQLTDLEHV
721: PPPGTRHPRW AHRQDAVSEA PLLEHQEEEE VFREDGQSMD GPHQATQVPE GTASKWGLVA
781: DRLLDLAASF SAVLTRIQVF VRRLLELHVF KLVALYTVWV ALKEVSVMNL LLVVLWAFAL
841: PYPRFRPMAS CLSTVWTCII IVCKMLYQLK IVNPHEYSSN CTEPFPNNTN LQPLEINQSL
901: LYRGPVDPAN WFGVRKGYPN LGYIQNHLQI LLLLVFEAVV YRRQEHYRRQ HQQAPLPAQA
961: VCADGTRQRL DQDLLSCLKY FINFFFYKFG LEICFLMAVN VIGQRMNFMV ILHGCWLVAI
1021: LTRRRREAIA RLWPNYCLFL TLFLLYQYLL CLGMPPALCI DYPWRWSKAI PMNSALIKWL
1081: YLPDFFRAPN STNLISDFLL LLCASQQWQV FSAERTEEWQ RMAGINTDHL EPLRGEPNPI
1141: PNFIHCRSYL DMLKVAVFRY LFWLVLVVVF VAGATRISIF GLGYLLACFY LLLFGTTLLQ
1201: KDTRAQLVLW DCLILYNVTV IISKNMLSLL SCVFVEQMQS NFCWVIQLFS LVCTVKGYYD
1261: PKEMMTRDRD CLLPVEEAGI IWDSICFFFL LLQRRIFLSH YFLHVSADLK ATALQASRGF
1321: ALYNAANLKS INFHRQIEEK SLAQLKRQMK RIRAKQEKYR QSQASRGQLQ SKDPQDPSQE
1381: PGPDSPGGSS PPRRQWWRPW LDHATVIHSG DYFLFESDSE EEEEALPEDP RPAAQSAFQM
1441: AYQAWVTNAQ TVLRQRRERA RQERAEQLAS GGDLNPDVEP VDVPEDEMAG RSHMMQRVLS
1501: TMQFLWVLGQ ATVDGLTRWL RAFTKHHRTM SDVLCAERYL LTQELLRVGE VRRGVLDQLY
1561: VGEDEATLSG PVETRDGPST ASSGLGAEEP LSSMTDDTSS PLSTGYNTRS GSEEIVTDAG
1621: DLQAGTSLHG SQELLANART RMRTASELLL DRRLHIPELE EAERFEAQQG RTLRLLRAGY
1681: QCVAAHSELL CYFIIILNHM VTASAASLVL PVLVFLWAML TIPRPSKRFW MTAIVFTEVM
1741: VVTKYLFQFG FFPWNSYVVL RRYENKPYFP PRILGLEKTD SYIKYDLVQL MALFFHRSQL
1801: LCYGLWDHEE DRYPKDHCRS SVKDREAKEE PEAKLESQSE TGTGHPKEPV LAGTPRDHIQ
1861: GKGSIRSKDV IQDPPEDLKP RHTRHISIRF RRRKETPGPK GTAVMETEHE EGEGKETTER
1921: KRPRHTQEKS KFRERMKAAG RRLQSFCVSL AQSFYQPLQR FFHDILHTKY RAATDVYALM
1981: FLADIVDIII IIFGFWAFGK HSAATDIASS LSDDQVPQAF LFMLLVQFGT MVIDRALYLR
2041: KTVLGKLAFQ VVLVVAIHIW MFFILPAVTE RMFSQNAVAQ LWYFVKCIYF ALSAYQIRCG
2101: YPTRILGNFL TKKYNHLNLF LFQGFRLVPF LVELRAVMDW VWTDTTLSLS NWMCVEDIYA
2161: NIFIIKCSRE TEKKYPQPKG QKKKKIVKYG MGGLIILFLI AIIWFPLLFM SLIRSVVGVV
2221: NQPIDVTVTL KLGGYEPLFT MSAQQPSIVP FTPQAYEELS QQFDPYPLAM QFISQYSPED
2281: IVTAQIEGSS GALWRISPPS RAQMKQELYN GTADITLRFT WNFQRDLAKG GTVEYTNEKH
2341: TLELAPNSTA RRQLAQLLEG RPDQSVVIPH LFPKYIRAPN GPEANPVKQL QPDEEEDYLG
2401: VRIQLRREQV GTGASGEQAG TKASDFLEWW VIELQDCKAD CNLLPMVIFS DKVSPPSLGF
2461: LAGYGIVGLY VSIVLVVGKF VRGFFSEISH SIMFEELPCV DRILKLCQDI FLVRETRELE
2521: LEEELYAKLI FLYRSPETMI KWTRERE