SCN5A_MOUSE
Domain
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
The IQ domain mediates association with calmodulin.
Function
Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. 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. 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).
Post-translational modifications
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).
Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2.
Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 868) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.
N-glycosylated at Asn-318, probably hinders potential interaction with regulatory subunits.
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily.
Tissue Specificity
Expressed in the myocardium (at protein level).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cytoplasm
- Perinuclear region
- Cell membrane
- Sarcolemma
- T-tubule
- Cell junction
- RANGRF promotes trafficking to the cell membrane. Colocalizes with PKP2 at intercalated disks in the heart (By similarity).
Alternative names
Sodium channel protein type 5 subunit alpha, Sodium channel protein cardiac muscle subunit alpha, Sodium channel protein type V subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.5, mH1, Scn5a