{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9H5I5","secondaryAccessions":["B7Z812","M4GPJ9","Q6ZS91","Q8N787","Q8NAR6","Q9H5R4"],"uniProtkbId":"PIEZ2_HUMAN","entryAudit":{"firstPublicDate":"2005-11-22","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-01-11","entryVersion":164,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Piezo-type mechanosensitive ion channel component 2"}},"alternativeNames":[{"fullName":{"value":"Protein FAM38B"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:26270"}],"value":"PIEZO2"},"synonyms":[{"value":"C18orf30"},{"value":"C18orf58"},{"value":"FAM38B"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CD54"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33057202"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"}],"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: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:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being 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 (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 (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). 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 (By similarity)"}],"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:0000250","source":"UniProtKB","id":"Q8CD54"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CD54"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"}],"value":"Regulated by auxillary subunits MDFIC and MDFI (PubMed:37590348). Channel activity is inhibited by TMEM120A (By similarity). Phosphatidic acid and lysophosphatidic acid inhibit PIEZO2 channel activity (By similarity)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CD54"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37590348"}],"value":"Homotrimer; the homotrimer forms a propeller-shaped Piezo channel with a cation-ion conducting pore (PubMed:37590348). Heterotrimeric interaction may occur between PIEZO1 and PIEZO2 (By similarity). Interacts with STOML3 (By similarity). Interacts with TMC7; the interaction inhibits PIEZO2-conducted mechanically activated currents (By similarity). Interacts with TMC1; the interaction may be part of the MET complex (By similarity). 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","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CD54"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8CD54"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q9H5I5-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q9H5I5-2"],"sequenceIds":["VSP_040472"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q9H5I5-3"],"sequenceIds":["VSP_040471"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q9H5I5-4"],"sequenceIds":["VSP_040630"],"isoformSequenceStatus":"Described"}]},{"commentType":"DISEASE","disease":{"diseaseId":"Arthrogryposis, distal, 5","diseaseAccession":"DI-04009","acronym":"DA5","description":"A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. 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Additional features include decreased muscular mass, failure to thrive, renal anomalies, hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna, and psychomotor retardation.","diseaseCrossReference":{"database":"MIM","id":"248700"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24726473"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Arthrogryposis, distal, with impaired proprioception and touch","diseaseAccession":"DI-04863","acronym":"DAIPT","description":"A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. 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