PIEZ1_HUMAN
ID PIEZ1_HUMAN Reviewed; 2521 AA.
AC Q92508; A6NHT9; A7E2B7; Q0KKZ9;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Piezo-type mechanosensitive ion channel component 1;
DE AltName: Full=Membrane protein induced by beta-amyloid treatment;
DE Short=Mib;
DE AltName: Full=Protein FAM38A;
GN Name=PIEZO1; Synonyms=FAM38A, KIAA0233;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 432-2521, AND TISSUE SPECIFICITY.
RX PubMed=16854388; DOI=10.1016/j.brainres.2006.06.050;
RA Satoh K., Hata M., Takahara S., Tsuzaki H., Yokota H., Akatsu H.,
RA Yamamoto T., Kosaka K., Yamada T.;
RT "A novel membrane protein, encoded by the gene covering KIAA0233, is
RT transcriptionally induced in senile plaque-associated astrocytes.";
RL Brain Res. 1108:19-27(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 486-2521.
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 486-2521.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 955-972; 1324-1334; 1548-1562 AND 1656-1671, VARIANTS
RP DHS1 ARG-2225 AND HIS-2456, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22529292; DOI=10.1182/blood-2012-04-422253;
RA Zarychanski R., Schulz V.P., Houston B.L., Maksimova Y., Houston D.S.,
RA Smith B., Rinehart J., Gallagher P.G.;
RT "Mutations in the mechanotransduction protein PIEZO1 are associated with
RT hereditary xerocytosis.";
RL Blood 120:1908-1915(2012).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1391; SER-1646 AND THR-1854,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2294.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1646, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20016066; DOI=10.1242/jcs.056424;
RA McHugh B.J., Buttery R., Lad Y., Banks S., Haslett C., Sethi T.;
RT "Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to
RT the endoplasmic reticulum.";
RL J. Cell Sci. 123:51-61(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1391 AND SER-1646, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-734; SER-758; SER-1391;
RP SER-1396; SER-1636; SER-1646 AND THR-1854, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1646, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=25119035; DOI=10.1038/nature13701;
RA Li J., Hou B., Tumova S., Muraki K., Bruns A., Ludlow M.J., Sedo A.,
RA Hyman A.J., McKeown L., Young R.S., Yuldasheva N.Y., Majeed Y.,
RA Wilson L.A., Rode B., Bailey M.A., Kim H.R., Fu Z., Carter D.A., Bilton J.,
RA Imrie H., Ajuh P., Dear T.N., Cubbon R.M., Kearney M.T., Prasad R.K.,
RA Evans P.C., Ainscough J.F., Beech D.J.;
RT "Piezo1 integration of vascular architecture with physiological force.";
RL Nature 515:279-282(2014).
RN [15]
RP FUNCTION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=29799007; DOI=10.1038/s41467-018-04436-w;
RA Tsuchiya M., Hara Y., Okuda M., Itoh K., Nishioka R., Shiomi A., Nagao K.,
RA Mori M., Mori Y., Ikenouchi J., Suzuki R., Tanaka M., Ohwada T., Aoki J.,
RA Kanagawa M., Toda T., Nagata Y., Matsuda R., Takayama Y., Tominaga M.,
RA Umeda M.;
RT "Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-
RT mediated myotube formation.";
RL Nat. Commun. 9:2049-2049(2018).
RN [16]
RP VARIANTS DHS1 SER-718; SER-782; GLN-808; LEU-1117; ASP-2003; VAL-2020;
RP MET-2127; 2166-LYS--LYS-2169 DEL; HIS-2456 AND GLN-2488, CHARACTERIZATION
RP OF VARIANTS DHS1 HIS-2456 AND GLN-2488, FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23479567; DOI=10.1182/blood-2013-02-482489;
RA Andolfo I., Alper S.L., De Franceschi L., Auriemma C., Russo R.,
RA De Falco L., Vallefuoco F., Esposito M.R., Vandorpe D.H., Shmukler B.E.,
RA Narayan R., Montanaro D., D'Armiento M., Vetro A., Limongelli I.,
RA Zuffardi O., Glader B.E., Schrier S.L., Brugnara C., Stewart G.W.,
RA Delaunay J., Iolascon A.;
RT "Multiple clinical forms of dehydrated hereditary stomatocytosis arise from
RT mutations in PIEZO1.";
RL Blood 121:3925-3935(2013).
RN [17]
RP VARIANTS DHS1 PRO-1358; THR-2020; MET-2127 AND LEU-GLU-2496 INS,
RP CHARACTERIZATION OF VARIANTS DHS1 PRO-1358; THR-2020; MET-2127;
RP LEU-GLU-2496 INS; ARG-2225 AND HIS-2456, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23695678; DOI=10.1038/ncomms2899;
RA Albuisson J., Murthy S.E., Bandell M., Coste B., Louis-Dit-Picard H.,
RA Mathur J., Feneant-Thibault M., Tertian G., de Jaureguiberry J.P.,
RA Syfuss P.Y., Cahalan S., Garcon L., Toutain F., Simon Rohrlich P.,
RA Delaunay J., Picard V., Jeunemaitre X., Patapoutian A.;
RT "Dehydrated hereditary stomatocytosis linked to gain-of-function mutations
RT in mechanically activated PIEZO1 ion channels.";
RL Nat. Commun. 4:1884-1884(2013).
RN [18]
RP VARIANTS DHS1 ARG-2225 AND HIS-2456, CHARACTERIZATION OF VARIANTS DHS1
RP ARG-2225 AND HIS-2456, AND MUTAGENESIS OF ARG-2456.
RX PubMed=23487776; DOI=10.1073/pnas.1219777110;
RA Bae C., Gnanasambandam R., Nicolai C., Sachs F., Gottlieb P.A.;
RT "Xerocytosis is caused by mutations that alter the kinetics of the
RT mechanosensitive channel PIEZO1.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1162-1168(2013).
RN [19]
RP VARIANT DHS1 HIS-2456.
RX PubMed=23973043; DOI=10.1016/j.bcmd.2013.07.015;
RA Shmukler B.E., Vandorpe D.H., Rivera A., Auerbach M., Brugnara C.,
RA Alper S.L.;
RT "Dehydrated stomatocytic anemia due to the heterozygous mutation R2456H in
RT the mechanosensitive cation channel PIEZO1: a case report.";
RL Blood Cells Mol. Dis. 52:53-54(2014).
RN [20]
RP VARIANT DHS1 HIS-2456.
RX PubMed=23581886; DOI=10.1111/cge.12147;
RA Beneteau C., Thierry G., Blesson S., Le Vaillant C., Picard V., Bene M.C.,
RA Eveillard M., Le Caignec C.;
RT "Recurrent mutation in the PIEZO1 gene in two families of hereditary
RT xerocytosis with fetal hydrops.";
RL Clin. Genet. 85:293-295(2014).
RN [21]
RP INVOLVEMENT IN LMPHM6, AND VARIANTS LMPHM6 MET-939; LEU-2430; CYS-2456 AND
RP LEU-2458.
RX PubMed=26333996; DOI=10.1038/ncomms9085;
RA Fotiou E., Martin-Almedina S., Simpson M.A., Lin S., Gordon K., Brice G.,
RA Atton G., Jeffery I., Rees D.C., Mignot C., Vogt J., Homfray T.,
RA Snyder M.P., Rockson S.G., Jeffery S., Mortimer P.S., Mansour S.,
RA Ostergaard P.;
RT "Novel mutations in PIEZO1 cause an autosomal recessive generalized
RT lymphatic dysplasia with non-immune hydrops fetalis.";
RL Nat. Commun. 6:8085-8085(2015).
CC -!- FUNCTION: Pore-forming subunit of a mechanosensitive non-specific
CC cation channel (PubMed:23479567, PubMed:23695678). Generates currents
CC characterized by a linear current-voltage relationship that are
CC sensitive to ruthenium red and gadolinium. Plays a key role in
CC epithelial cell adhesion by maintaining integrin activation through R-
CC Ras recruitment to the ER, most probably in its activated state, and
CC subsequent stimulation of calpain signaling (PubMed:20016066). In the
CC kidney, may contribute to the detection of intraluminal pressure
CC changes and to urine flow sensing. Acts as shear-stress sensor that
CC promotes endothelial cell organization and alignment in the direction
CC of blood flow through calpain activation (PubMed:25119035). Plays a key
CC role in blood vessel formation and vascular structure in both
CC development and adult physiology (By similarity). Acts as sensor of
CC phosphatidylserine (PS) flipping at the plasma membrane and governs
CC morphogenesis of muscle cells. In myoblasts, flippase-mediated PS
CC enrichment at the inner leaflet of plasma membrane triggers channel
CC activation and Ca2+ influx followed by Rho GTPases signal transduction,
CC leading to assembly of cortical actomyosin fibers and myotube
CC formation. {ECO:0000250|UniProtKB:E2JF22, ECO:0000269|PubMed:20016066,
CC ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:23695678,
CC ECO:0000269|PubMed:25119035, ECO:0000269|PubMed:29799007}.
CC -!- ACTIVITY REGULATION: Down-regulated by phosphatidylserines exposed on
CC the cell surface. {ECO:0000269|PubMed:29799007}.
CC -!- SUBUNIT: Homotrimer. Interacts with PKD2. Interacts with STOML3.
CC {ECO:0000250|UniProtKB:E2JF22}.
CC -!- INTERACTION:
CC Q92508; P04155: TFF1; NbExp=5; IntAct=EBI-10986212, EBI-743871;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20016066}; Multi-pass membrane protein. Endoplasmic
CC reticulum-Golgi intermediate compartment membrane
CC {ECO:0000250|UniProtKB:Q0KL00}. Cell membrane
CC {ECO:0000269|PubMed:22529292, ECO:0000269|PubMed:23479567}; Multi-pass
CC membrane protein {ECO:0000305}. Cell projection, lamellipodium membrane
CC {ECO:0000269|PubMed:25119035}. Cell membrane
CC {ECO:0000250|UniProtKB:E2JF22}; Multi-pass membrane protein. Note=In
CC erythrocytes, located in the plasma membrane (PubMed:22529292,
CC PubMed:23479567). Accumulates at the leading apical lamellipodia of
CC endothelial cells in response to shear stress (PubMed:25119035).
CC Colocalizes with F-actin and MYH9 at the actomyosin cortex in
CC myoblasts. {ECO:0000250|UniProtKB:E2JF22, ECO:0000269|PubMed:22529292,
CC ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:25119035}.
CC -!- TISSUE SPECIFICITY: Expressed in numerous tissues. In normal brain,
CC expressed exclusively in neurons, not in astrocytes. In Alzheimer
CC disease brains, expressed in about half of the activated astrocytes
CC located around classical senile plaques. In Parkinson disease
CC substantia nigra, not detected in melanin-containing neurons nor in
CC activated astrocytes. Expressed in erythrocytes (at protein level).
CC Expressed in myoblasts (at protein level).
CC {ECO:0000269|PubMed:16854388, ECO:0000269|PubMed:22529292,
CC ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:29799007}.
CC -!- DEVELOPMENTAL STAGE: At 17 weeks of gestation, strongly expressed in
CC hepatic erythroblasts. At that stage, also expressed in fetal splenic
CC plasma cells and in lymphatic vessel of fetal peritoneum. In vitro, up-
CC regulated during the erythroid differentiation of CD34+ cells from
CC healthy donors (at protein level). {ECO:0000269|PubMed:23479567}.
CC -!- DISEASE: Dehydrated hereditary stomatocytosis 1 with or without
CC pseudohyperkalemia and/or perinatal edema (DHS1) [MIM:194380]: An
CC autosomal dominant hemolytic anemia characterized by primary
CC erythrocyte dehydration. DHS erythrocytes exhibit decreased total
CC cation and potassium content that are not accompanied by a proportional
CC net gain of sodium and water. DHS patients typically exhibit mild to
CC moderate compensated hemolytic anemia, with an increased erythrocyte
CC mean corpuscular hemoglobin concentration and a decreased osmotic
CC fragility, both of which reflect cellular dehydration. Patients may
CC also show perinatal edema and pseudohyperkalemia due to loss of
CC potassium from red cells stored at room temperature. A minor proportion
CC of red cells appear as stomatocytes on blood films. Complications such
CC as splenomegaly and cholelithiasis, resulting from increased red cell
CC trapping in the spleen and elevated bilirubin levels, respectively, may
CC occur. The course of DHS is frequently associated with iron overload,
CC which may lead to hepatosiderosis. {ECO:0000269|PubMed:22529292,
CC ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:23487776,
CC ECO:0000269|PubMed:23581886, ECO:0000269|PubMed:23695678,
CC ECO:0000269|PubMed:23973043}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. All disease-causing
CC mutations characterized so far produce a gain-of-function phenotype,
CC mutated channels exhibiting increased cation transport in erythroid
CC cells, that could be due to slower channel inactivation rate compared
CC to the wild-type protein.
CC -!- DISEASE: Lymphatic malformation 6 (LMPHM6) [MIM:616843]: A form of
CC primary lymphedema, a disease characterized by swelling of body parts
CC due to developmental anomalies and functional defects of the lymphatic
CC system. Patients with lymphedema may suffer from recurrent local
CC infections. LMPHM6 is an autosomal recessive, severe form manifesting
CC as generalized lymphatic dysplasia. It is characterized by uniform,
CC widespread swelling of all segments of the body, with systemic
CC involvement such as intestinal and/or pulmonary lymphangiectasia,
CC pleural effusions, chylothoraces and/or pericardial effusions, and with
CC a high incidence of non- immune hydrops fetalis.
CC {ECO:0000269|PubMed:26333996}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Piezo comes from the Greek 'piesi' meaning pressure.
CC -!- SIMILARITY: Belongs to the PIEZO (TC 1.A.75) family. {ECO:0000305}.
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DR EMBL; AC138028; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB161230; BAF03565.1; -; mRNA.
DR EMBL; D87071; BAA13240.1; -; mRNA.
DR EMBL; BC150271; AAI50272.1; -; mRNA.
DR CCDS; CCDS54058.1; -.
DR RefSeq; NP_001136336.2; NM_001142864.3.
DR AlphaFoldDB; Q92508; -.
DR SMR; Q92508; -.
DR BioGRID; 115124; 57.
DR IntAct; Q92508; 18.
DR MINT; Q92508; -.
DR STRING; 9606.ENSP00000301015; -.
DR GuidetoPHARMACOLOGY; 2945; -.
DR TCDB; 1.A.75.1.1; the mechanical nociceptor, piezo (piezo) family.
DR GlyGen; Q92508; 3 sites.
DR iPTMnet; Q92508; -.
DR PhosphoSitePlus; Q92508; -.
DR SwissPalm; Q92508; -.
DR BioMuta; PIEZO1; -.
DR DMDM; 317373533; -.
DR EPD; Q92508; -.
DR jPOST; Q92508; -.
DR MassIVE; Q92508; -.
DR MaxQB; Q92508; -.
DR PaxDb; Q92508; -.
DR PeptideAtlas; Q92508; -.
DR PRIDE; Q92508; -.
DR ProteomicsDB; 75277; -.
DR Antibodypedia; 44957; 181 antibodies from 23 providers.
DR DNASU; 9780; -.
DR Ensembl; ENST00000301015.14; ENSP00000301015.9; ENSG00000103335.22.
DR GeneID; 9780; -.
DR KEGG; hsa:9780; -.
DR MANE-Select; ENST00000301015.14; ENSP00000301015.9; NM_001142864.4; NP_001136336.2.
DR UCSC; uc010vpb.3; human.
DR CTD; 9780; -.
DR DisGeNET; 9780; -.
DR GeneCards; PIEZO1; -.
DR HGNC; HGNC:28993; PIEZO1.
DR HPA; ENSG00000103335; Low tissue specificity.
DR MalaCards; PIEZO1; -.
DR MIM; 194380; phenotype.
DR MIM; 611184; gene.
DR MIM; 616843; phenotype.
DR neXtProt; NX_Q92508; -.
DR OpenTargets; ENSG00000103335; -.
DR Orphanet; 3202; Dehydrated hereditary stomatocytosis.
DR VEuPathDB; HostDB:ENSG00000103335; -.
DR eggNOG; KOG1893; Eukaryota.
DR GeneTree; ENSGT00940000157348; -.
DR HOGENOM; CLU_000512_0_0_1; -.
DR InParanoid; Q92508; -.
DR OMA; QRGNDIQ; -.
DR OrthoDB; 13738at2759; -.
DR PhylomeDB; Q92508; -.
DR TreeFam; TF314295; -.
DR PathwayCommons; Q92508; -.
DR SignaLink; Q92508; -.
DR SIGNOR; Q92508; -.
DR BioGRID-ORCS; 9780; 24 hits in 1086 CRISPR screens.
DR ChiTaRS; PIEZO1; human.
DR GenomeRNAi; 9780; -.
DR Pharos; Q92508; Tchem.
DR PRO; PR:Q92508; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q92508; protein.
DR Bgee; ENSG00000103335; Expressed in muscle layer of sigmoid colon and 92 other tissues.
DR ExpressionAtlas; Q92508; baseline and differential.
DR Genevisible; Q92508; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005261; F:cation channel activity; ISS:UniProtKB.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IBA:GO_Central.
DR GO; GO:0006812; P:cation transport; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IBA:GO_Central.
DR GO; GO:0050982; P:detection of mechanical stimulus; IBA:GO_Central.
DR GO; GO:0033634; P:positive regulation of cell-cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0033625; P:positive regulation of integrin activation; IMP:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IMP:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR InterPro; IPR027272; Piezo.
DR InterPro; IPR031805; Piezo_dom.
DR InterPro; IPR031334; Piezo_RRas-bd_dom.
DR PANTHER; PTHR13167; PTHR13167; 3.
DR Pfam; PF15917; PIEZO; 1.
DR Pfam; PF12166; Piezo_RRas_bdg; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Coiled coil; Direct protein sequencing;
KW Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Hereditary hemolytic anemia; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..2521
FT /note="Piezo-type mechanosensitive ion channel component 1"
FT /id="PRO_0000186817"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..84
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 194..214
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 218..238
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 460..480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 514..534
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 579..599
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 602..622
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 629..649
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 681..701
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 823..843
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 852..872
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 926..946
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 987..1007
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1043..1063
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1160..1180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1184..1204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1218..1240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1247..1264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1277..1297
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1678..1698
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1700..1720
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1734..1754
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1962..1982
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2003..2023
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2032..2052
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2061..2081
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2100..2122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2129..2149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 2177..2197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2198..2431
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:E2JF22"
FT TRANSMEM 2432..2452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 738..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1356..1402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1462..1498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1576..1630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1811..1921
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1339..1368
FT /evidence="ECO:0000255"
FT COMPBIAS 746..760
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1356..1377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1576..1598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1605..1620
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1811..1826
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 734
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 758
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1396
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1636
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1646
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1854
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 2411..2415
FT /evidence="ECO:0000250|UniProtKB:E2JF22"
FT VARIANT 718
FT /note="G -> S (in DHS1; dbSNP:rs755885744)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069822"
FT VARIANT 782
FT /note="G -> S (in DHS1; dbSNP:rs200970763)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069823"
FT VARIANT 808
FT /note="R -> Q (in DHS1; dbSNP:rs202103485)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069824"
FT VARIANT 939
FT /note="L -> M (in LMPHM6; unknown pathological
FT significance; dbSNP:rs201226914)"
FT /evidence="ECO:0000269|PubMed:26333996"
FT /id="VAR_076407"
FT VARIANT 1117
FT /note="S -> L (in DHS1; dbSNP:rs587777765)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069825"
FT VARIANT 1358
FT /note="R -> P (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents; dbSNP:rs587776990)"
FT /evidence="ECO:0000269|PubMed:23695678"
FT /id="VAR_069826"
FT VARIANT 2003
FT /note="A -> D (in DHS1)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069827"
FT VARIANT 2020
FT /note="A -> T (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents; dbSNP:rs587776989)"
FT /evidence="ECO:0000269|PubMed:23695678"
FT /id="VAR_069828"
FT VARIANT 2020
FT /note="A -> V (in DHS1; dbSNP:rs587777764)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069829"
FT VARIANT 2127
FT /note="T -> M (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents; dbSNP:rs587776991)"
FT /evidence="ECO:0000269|PubMed:23479567,
FT ECO:0000269|PubMed:23695678"
FT /id="VAR_069830"
FT VARIANT 2166..2169
FT /note="Missing (in DHS1)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069831"
FT VARIANT 2225
FT /note="M -> R (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents; dbSNP:rs587776987)"
FT /evidence="ECO:0000269|PubMed:22529292,
FT ECO:0000269|PubMed:23487776, ECO:0000269|PubMed:23695678"
FT /id="VAR_069832"
FT VARIANT 2430
FT /note="P -> L (in LMPHM6; unknown pathological
FT significance; dbSNP:rs869025601)"
FT /evidence="ECO:0000269|PubMed:26333996"
FT /id="VAR_076408"
FT VARIANT 2456
FT /note="R -> C (in LMPHM6; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26333996"
FT /id="VAR_076409"
FT VARIANT 2456
FT /note="R -> H (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents; dbSNP:rs587776988)"
FT /evidence="ECO:0000269|PubMed:22529292,
FT ECO:0000269|PubMed:23479567, ECO:0000269|PubMed:23487776,
FT ECO:0000269|PubMed:23581886, ECO:0000269|PubMed:23695678,
FT ECO:0000269|PubMed:23973043"
FT /id="VAR_069833"
FT VARIANT 2458
FT /note="F -> L (in LMPHM6; unknown pathological
FT significance; dbSNP:rs577860843)"
FT /evidence="ECO:0000269|PubMed:26333996"
FT /id="VAR_076410"
FT VARIANT 2488
FT /note="R -> Q (in DHS1; increased cation transport in
FT erythroid cells; dbSNP:rs749288233)"
FT /evidence="ECO:0000269|PubMed:23479567"
FT /id="VAR_069834"
FT VARIANT 2496
FT /note="E -> ELE (in DHS1; gives rise to mechanically
FT activated currents that inactivate more slowly than wild-
FT type currents)"
FT /evidence="ECO:0000269|PubMed:23695678"
FT /id="VAR_069835"
FT MUTAGEN 2456
FT /note="R->K: Does not inactivate the protein. gives rise to
FT mechanically activated currents that inactivate more slowly
FT than wild-type currents, suggesting it could shift the
FT channel kinetics from phasic to tonic."
FT /evidence="ECO:0000269|PubMed:23487776"
FT CONFLICT 750
FT /note="Missing (in Ref. 3; BAA13240 and 4; AAI50272)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2521 AA; 286790 MW; 127A3DA3E7CBD2DD CRC64;
MEPHVLGAVL YWLLLPCALL AACLLRFSGL SLVYLLFLLL LPWFPGPTRC GLQGHTGRLL
RALLGLSLLF LVAHLALQIC LHIVPRLDQL LGPSCSRWET LSRHIGVTRL DLKDIPNAIR
LVAPDLGILV VSSVCLGICG RLARNTRQSP HPRELDDDER DVDASPTAGL QEAATLAPTR
RSRLAARFRV TAHWLLVAAG RVLAVTLLAL AGIAHPSALS SVYLLLFLAL CTWWACHFPI
STRGFSRLCV AVGCFGAGHL ICLYCYQMPL AQALLPPAGI WARVLGLKDF VGPTNCSSPH
ALVLNTGLDW PVYASPGVLL LLCYATASLR KLRAYRPSGQ RKEAAKGYEA RELELAELDQ
WPQERESDQH VVPTAPDTEA DNCIVHELTG QSSVLRRPVR PKRAEPREAS PLHSLGHLIM
DQSYVCALIA MMVWSITYHS WLTFVLLLWA CLIWTVRSRH QLAMLCSPCI LLYGMTLCCL
RYVWAMDLRP ELPTTLGPVS LRQLGLEHTR YPCLDLGAML LYTLTFWLLL RQFVKEKLLK
WAESPAALTE VTVADTEPTR TQTLLQSLGE LVKGVYAKYW IYVCAGMFIV VSFAGRLVVY
KIVYMFLFLL CLTLFQVYYS LWRKLLKAFW WLVVAYTMLV LIAVYTFQFQ DFPAYWRNLT
GFTDEQLGDL GLEQFSVSEL FSSILVPGFF LLACILQLHY FHRPFMQLTD MEHVSLPGTR
LPRWAHRQDA VSGTPLLREE QQEHQQQQQE EEEEEEDSRD EGLGVATPHQ ATQVPEGAAK
WGLVAERLLE LAAGFSDVLS RVQVFLRRLL ELHVFKLVAL YTVWVALKEV SVMNLLLVVL
WAFALPYPRF RPMASCLSTV WTCVIIVCKM LYQLKVVNPQ EYSSNCTEPF PNSTNLLPTE
ISQSLLYRGP VDPANWFGVR KGFPNLGYIQ NHLQVLLLLV FEAIVYRRQE HYRRQHQLAP
LPAQAVFASG TRQQLDQDLL GCLKYFINFF FYKFGLEICF LMAVNVIGQR MNFLVTLHGC
WLVAILTRRH RQAIARLWPN YCLFLALFLL YQYLLCLGMP PALCIDYPWR WSRAVPMNSA
LIKWLYLPDF FRAPNSTNLI SDFLLLLCAS QQWQVFSAER TEEWQRMAGV NTDRLEPLRG
EPNPVPNFIH CRSYLDMLKV AVFRYLFWLV LVVVFVTGAT RISIFGLGYL LACFYLLLFG
TALLQRDTRA RLVLWDCLIL YNVTVIISKN MLSLLACVFV EQMQTGFCWV IQLFSLVCTV
KGYYDPKEMM DRDQDCLLPV EEAGIIWDSV CFFFLLLQRR VFLSHYYLHV RADLQATALL
ASRGFALYNA ANLKSIDFHR RIEEKSLAQL KRQMERIRAK QEKHRQGRVD RSRPQDTLGP
KDPGLEPGPD SPGGSSPPRR QWWRPWLDHA TVIHSGDYFL FESDSEEEEE AVPEDPRPSA
QSAFQLAYQA WVTNAQAVLR RRQQEQEQAR QEQAGQLPTG GGPSQEVEPA EGPEEAAAGR
SHVVQRVLST AQFLWMLGQA LVDELTRWLQ EFTRHHGTMS DVLRAERYLL TQELLQGGEV
HRGVLDQLYT SQAEATLPGP TEAPNAPSTV SSGLGAEEPL SSMTDDMGSP LSTGYHTRSG
SEEAVTDPGE REAGASLYQG LMRTASELLL DRRLRIPELE EAELFAEGQG RALRLLRAVY
QCVAAHSELL CYFIIILNHM VTASAGSLVL PVLVFLWAML SIPRPSKRFW MTAIVFTEIA
VVVKYLFQFG FFPWNSHVVL RRYENKPYFP PRILGLEKTD GYIKYDLVQL MALFFHRSQL
LCYGLWDHEE DSPSKEHDKS GEEEQGAEEG PGVPAATTED HIQVEARVGP TDGTPEPQVE
LRPRDTRRIS LRFRRRKKEG PARKGAAAIE AEDREEEEGE EEKEAPTGRE KRPSRSGGRV
RAAGRRLQGF CLSLAQGTYR PLRRFFHDIL HTKYRAATDV YALMFLADVV DFIIIIFGFW
AFGKHSAATD ITSSLSDDQV PEAFLVMLLI QFSTMVVDRA LYLRKTVLGK LAFQVALVLA
IHLWMFFILP AVTERMFNQN VVAQLWYFVK CIYFALSAYQ IRCGYPTRIL GNFLTKKYNH
LNLFLFQGFR LVPFLVELRA VMDWVWTDTT LSLSSWMCVE DIYANIFIIK CSRETEKKYP
QPKGQKKKKI VKYGMGGLII LFLIAIIWFP LLFMSLVRSV VGVVNQPIDV TVTLKLGGYE
PLFTMSAQQP SIIPFTAQAY EELSRQFDPQ PLAMQFISQY SPEDIVTAQI EGSSGALWRI
SPPSRAQMKR ELYNGTADIT LRFTWNFQRD LAKGGTVEYA NEKHMLALAP NSTARRQLAS
LLEGTSDQSV VIPNLFPKYI RAPNGPEANP VKQLQPNEEA DYLGVRIQLR REQGAGATGF
LEWWVIELQE CRTDCNLLPM VIFSDKVSPP SLGFLAGYGI MGLYVSIVLV IGKFVRGFFS
EISHSIMFEE LPCVDRILKL CQDIFLVRET RELELEEELY AKLIFLYRSP ETMIKWTREK
E
