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)
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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
- defects in SCN5A are a cause of
- defects in SCN5A are the cause of
- long QT syndrome type 3
- Brugada syndrome
- sick sinus syndrome type 1
- cardiomyopathy dilated type 1E
Notes
- Na+ channels in mammalian cardiac membrane have functional properties quite distinct from Na+ channels in nerve & skeletal muscle
More general terms
Additional terms
- 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
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q14524.html
- ↑ LQTSdb; SCN5A mutations page http://www.ssi.dk/graphics/html/lqtsdb/scn5a.htm
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=SCN5A
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6331
- OMIM: https://mirror.omim.org/entry/108770
- OMIM: https://mirror.omim.org/entry/113900
- OMIM: https://mirror.omim.org/entry/272120
- OMIM: https://mirror.omim.org/entry/600163
- OMIM: https://mirror.omim.org/entry/601144
- OMIM: https://mirror.omim.org/entry/601154
- OMIM: https://mirror.omim.org/entry/603829
- OMIM: https://mirror.omim.org/entry/603830
- OMIM: https://mirror.omim.org/entry/608567
- UniProt: http://www.uniprot.org/uniprot/Q14524.html