{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9JJV9","secondaryAccessions":["E9Q1D2","Q3UH91"],"uniProtkbId":"SCN5A_MOUSE","entryAudit":{"firstPublicDate":"2009-06-16","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-07-27","entryVersion":170,"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":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Sodium channel protein type 5 subunit alpha"}},"alternativeNames":[{"fullName":{"value":"Sodium channel protein cardiac muscle subunit alpha"}},{"fullName":{"value":"Sodium channel protein type V subunit alpha"}},{"fullName":{"value":"Voltage-gated sodium channel subunit alpha Nav1.5"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11834499"}],"value":"mH1"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"MGI","id":"MGI:98251"}],"value":"Scn5a"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11834499"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23420830"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29306897"}],"value":"Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes (By similarity). Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient (By similarity). The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:11834499, PubMed:23420830). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11834499, PubMed:23420830, PubMed:29306897). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (PubMed:29306897)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"Na(+)(in) = Na(+)(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:34963"},{"database":"ChEBI","id":"CHEBI:29101"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11834499"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"}],"value":"Channel inactivation is regulated by intracellular calcium levels (By similarity). It is a tetrodotoxin-resistant voltage-gated Na(+) channel (Nav) (By similarity)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15389"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21817159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29306897"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9412493"}],"value":"Interact with regulatory subunit SCN1B (By similarity). May not form the same regulatory interactions with beta subunits as other Navs do (By similarity). Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (PubMed:9412493). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L (By similarity). Interacts with CALM (By similarity). Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function (PubMed:21817159). Interacts with FGF12 and FGF14 (By similarity). Interacts with ANK3 (By similarity). Interacts with PKP2 (via N-terminus) (By similarity). Interacts with TMEM233 (By similarity). Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (PubMed:29306897)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9JJV9","intActId":"EBI-8313814"},"interactantTwo":{"uniProtKBAccession":"Q4U4S6","geneName":"Xirp2","intActId":"EBI-10768169"},"numberOfExperiments":2,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P15389"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23420830"}],"value":"RANGRF promotes trafficking to the cell membrane. 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Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"}],"value":"The IQ domain mediates association with calmodulin"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17124532"}],"value":"Phosphorylation at Ser-1505 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents (By similarity). Regulated through phosphorylation by CaMK2D (PubMed:17124532)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q14524"}],"value":"Ubiquitinated by NEDD4L; which promotes its endocytosis. 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