{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8CD54","secondaryAccessions":["E2JF23","Q8BSM4","Q9D341"],"uniProtkbId":"PIEZ2_MOUSE","entryAudit":{"firstPublicDate":"2005-11-22","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-01-11","entryVersion":144,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Mus musculus","commonName":"Mouse","taxonId":10090,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Glires","Rodentia","Myomorpha","Muroidea","Muridae","Murinae","Mus","Mus"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Piezo-type mechanosensitive ion channel component 2"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"20813920"}],"value":"Protein FAM38B"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:1918781"}],"value":"Piezo2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"20813920"}],"value":"Fam38b"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20813920"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24717433"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25471886"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26551544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28002412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31435011"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33057202"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39919739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41349545"}],"value":"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:24717433, PubMed:31435011, 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:31435011, PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (PubMed:26551544, PubMed:28002412, PubMed:33057202, PubMed:39919739). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (PubMed:28002412). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (PubMed:39919739). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons and is required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, Piezo2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (PubMed:26551544). 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). Required for Merkel-cell mechanotransduction (PubMed:24717433). Plays a major role in light-touch mechanosensation (PubMed:25471886). In kidney, during blood volume challenges, regulates calcium dynamics and maintains renin production, thereby serving as an essential regulator of the renin-angiotensin-aldosterone system (RAAS) and systemic blood volume control (PubMed:41349545)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Ca(2+)(in) = Ca(2+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29671"},{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31435011"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35819364"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39147733"}],"value":"Regulated by auxillary subunits MDFIC and MDFI (PubMed:37590348). Channel activity is inhibited by TMEM120aa (PubMed:35819364). Phosphatidic acid and lysophosphatidic acid inhibit Piezo2 channel activity (PubMed:39147733)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22343900"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24662763"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31435011"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38568807"}],"value":"Homotrimer; the homotrimer forms a propeller-shaped Piezo channel with a cation-ion conducting pore (PubMed:37590348, PubMed:31435011). Heterotrimeric interaction may occur between PIEZO1 and PIEZO2 (PubMed:38228630). Interacts with STOM13. Interacts with TMC7; the interaction inhibits PIEZO2-conducted mechanically activated currents (PubMed:38568807). Interacts with TMC1; the interaction may be part of the MET complex (PubMed:38228630). Interacts with MDFIC (via C-terminus); the interaction prolongs Piezo channel inactivation (PubMed:37590348). Interacts with MDFI (via C-terminus); the interaction prolongs Piezo channel inactivation (PubMed:37590348)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"}],"value":"Located at the tips and sides of stereocilia and cuticular plate membranes"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"25471886"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31435011"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q8CD54-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q8CD54-2"],"sequenceIds":["VSP_040473","VSP_040474"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q8CD54-3"],"sequenceIds":["VSP_040631","VSP_040632"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20813920"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24662763"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24717433"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25471886"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26551544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28002412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33057202"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38568807"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39919739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"41349545"}],"value":"Expressed in bladder, colon, and lung, but less abundant in kidney or skin (PubMed:20813920). Strong expression is observed in dorsal root ganglia (DRG) sensory neurons (PubMed:20813920, PubMed:38568807). Expressed in a wide range of cutaneous low-threshold mechanoreceptors (LTMRs), including Merkel cells and Meissner's corpuscles (PubMed:24717433, PubMed:25471886). Expressed in sensory neurons (PubMed:24662763, PubMed:28002412, PubMed:33057202, PubMed:39919739). Expressed in cochlear inner and outer hair cells and vestibular organ hair cells (PubMed:38228630). Expressed in pulmonary neuroepithelial cell bodies (PubMed:28002412). Expressed in bladder urothelium and sensory neurons of the lower urinary tract (PubMed:33057202). Expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs (PubMed:26551544). Expressed in kidney juxtaglomerular granular and mesangial cells (PubMed:41349545)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25471886"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26551544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28002412"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38228630"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39919739"}],"value":"Perinatal lethality. Pups show signs of respiratory distress, such as cyanosis and gasping and also failed to suckle and die within 24h of birth (PubMed:25471886, PubMed:28002412). Conditional knockout in sensory neurons and Merkel cells causes severe defects in light-touch sensation, although detection of pain (nociception) is unaffected (PubMed:25471886). Conditional knockout in inner ear hair cells show no auditory and vestibular defects (PubMed:38228630). Conditional knockout in sensory neurons leads to lower body weight, primarily due to a reduction in fat mas with reduced mobility and similar food intake. Conditional knockout also exhibit reduced fasting blood glucose levels and increased glucose tolerance, as well as reduced fasting insulin levels and increased insulin sensitivity (PubMed:39919739). Conditional knockout in proprioceptors causes severe impairment in limb coordination (PubMed:26551544)"}],"commentType":"DISRUPTION PHENOTYPE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"20813920"}],"value":"Piezo comes from the Greek 'piesi' meaning pressure"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Due to intron retention"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the PIEZO (TC 1.A.75) family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAB31242.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAC27312.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE 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