Na+ channel protein type 5 subunit alpha; Na+ channel protein type V subunit alpha; voltage-gated Na+ channel subunit alpha Nav1.5; Na+ channel protein cardiac muscle subunit alpha; HH1 (SCN5A)

Function: - mediates the voltage-dependent Na⁺ permeability of excitable membranes - assumes opened or closed conformation in response to voltage difference across the membrane - forms a Na⁺-selective channel through which Na⁺ ions may pass in accordance with their electrochemical gradient - tetrodotoxin-resistant Na⁺ channel isoform - responsible for the initial upstroke of the action potential in the electrocardiogram - ubiquitinated by NEDD4L; which promotes its endocytosis - does not seem to be ubiquitinated by NEDD4 or WWP2 - interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 & SNTB2 (putative) - interacts with NEDD4, NEDD4L & WWP2 Structure: - 24 transmembrane domains - contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) & one positively charged segment (S4) - segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every 3rd position - belongs to the Na⁺ channel family - contains 1 IQ domain Compartment: membrane Alternative splicing: named isoforms=6 Expression: - found in jejunal circular smooth muscle cells (at protein level) - expressed in human atrial & ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen - isoform 4 is expressed in brain Pathology: 1) defects in SCN5A are a cause of a) progressive familial heart block type 1A (PFHB1A) b) paroxysmal familial ventricular fibrillation c) sudden infant death syndrome (SIDS) d) familial atrial standstill 2) defects in SCN5A are the cause of a) long QT syndrome type 3 b) Brugada syndrome c) sick sinus syndrome type 1 d) cardiomyopathy dilated type 1E Notes: - Na⁺ channels in mammalian cardiac membrane have functional properties quite distinct from Na⁺ channels in nerve & skeletal muscle

Related

Brugada syndrome long QT syndrome type 3 progressive familial heart block type 1A; Lenegre-Lev disease; progressive cardiac conduction defect (PCCD, PFHB1A) sudden infant death syndrome (SIDS); includes; accidental infant strangulations & suffocations voltage-dependent Na+ channel

General

glycoprotein voltage-dependent Na+ channel protein alpha subunit

Properties

SIZE: entity length = 2016 aa MW = 227 kD COMPARTMENT: cellular membrane MOTIF: transmembrane domain {127-150} transmembrane domain {159-178} transmembrane domain {192-210} N-glycosylation site {N214} transmembrane domain {217-236} transmembrane domain {253-276} N-glycosylation site {N283} N-glycosylation site {N288} N-glycosylation site {N291} N-glycosylation site {N318} N-glycosylation site {N328} transmembrane domain {390-415} N-glycosylation site {N548} N-glycosylation site {N592} transmembrane domain {712-736} N-glycosylation site {N740} transmembrane domain {748-771} transmembrane domain {780-799} N-glycosylation site {N803} transmembrane domain {806-825} N-glycosylation site {N841} transmembrane domain {842-862} N-glycosylation site {N864} transmembrane domain {914-939} N-glycosylation site {N946} transmembrane domain {1201-1224} transmembrane domain {1238-1263} transmembrane domain {1270-1291} transmembrane domain {1296-1317} transmembrane domain {1337-1359} N-glycosylation site {N1365} N-glycosylation site {N1374} N-glycosylation site {N1380} N-glycosylation site {N1388} transmembrane domain {1444-1470} transmembrane domain {1524-1547} transmembrane domain {1559-1582} transmembrane domain {1589-1612} transmembrane domain {1623-1644} transmembrane domain {1660-1682} N-glycosylation site {N1736} transmembrane domain {1748-1772} N-glycosylation site {N1774} IQ motif {1901-1930} N-glycosylation site {N1955} NEDD4, NEDD4L and WWP2 interaction {1974-1977}

Database Correlations

OMIM correlations MORBIDMAP 600163 UniProt Q14524 PFAM correlations Entrez Gene 6331