SCN2A

Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants.

Full Name

Sodium Voltage-Gated Channel Alpha Subunit 2

Function

Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient (PubMed:1325650, PubMed:17021166, PubMed:28256214, PubMed:29844171).
Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (By similarity).

Biological Process

Biological Process cellular response to hypoxiaISS:UniProtKB
Biological Process intrinsic apoptotic signaling pathway in response to osmotic stressISS:UniProtKB
Biological Process membrane depolarization during action potentialManual Assertion Based On ExperimentIBA:GO_Central
Biological Process memoryISS:UniProtKB
Biological Process myelinationISS:BHF-UCL
Biological Process nervous system developmentISS:UniProtKB
Biological Process neuron apoptotic processISS:UniProtKB
Biological Process neuronal action potentialManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of ion transmembrane transportIEA:UniProtKB-KW
Biological Process sodium ion transmembrane transportISS:UniProtKB
Biological Process sodium ion transportISS:UniProtKB

Cellular Location

Cell membrane

Involvement in disease

Seizures, benign familial infantile, 3 (BFIS3):
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant.
Developmental and epileptic encephalopathy 11 (DEE11):
An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Episodic ataxia 9 (EA9):
An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development.

PTM

May be ubiquitinated by NEDD4L; which would promote its endocytosis.
Phosphorylation at Ser-1506 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
Sumoylated at Lys-38. Sumoylation is induced by hypoxia, increases voltage-gated sodium current and mediates the early response to acute hypoxia in neurons. Sumoylated SCN2A is located at the cell membrane.