InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SCN4A

Summary

InnateDB Protein

IDBP-383406.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SCN4A

Protein Name

sodium channel, voltage-gated, type IV, alpha subunit

Synonyms

HOKPP2; HYKPP; HYPP; Na(V)1.4; NAC1A; Nav1.4; SkM1;

Species

Homo sapiens

Ensembl Protein

ENSP00000396320

InnateDB Gene

IDBG-64440 (SCN4A)

Protein Structure

UniProt Annotation

Function

This protein 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. This sodium channel may be present in both denervated and innervated skeletal muscle.

Subcellular Localization

Membrane; Multi-pass membrane protein.

Disease Associations

Paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP. {ECO:0000269PubMed:10369308, ECO:0000269PubMed:10727489, ECO:0000269PubMed:1310898, ECO:0000269PubMed:1316765, ECO:0000269PubMed:1338909, ECO:0000269PubMed:15790667, ECO:0000269PubMed:16786525, ECO:0000269PubMed:18166706, ECO:0000269PubMed:19077043, ECO:0000269PubMed:20076800, ECO:0000269PubMed:8242056, ECO:0000269PubMed:8308722, ECO:0000269PubMed:8388676, ECO:0000269PubMed:8580427}. Note=The disease is caused by mutations affecting the gene represented in this entry.Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269PubMed:10599760, ECO:0000269PubMed:10851391, ECO:0000269PubMed:10944223, ECO:0000269PubMed:11558801, ECO:0000269PubMed:11591859, ECO:0000269PubMed:18162704, ECO:0000269PubMed:19118277, ECO:0000269PubMed:20522878, ECO:0000269PubMed:21043388}. Note=The disease is caused by mutations affecting the gene represented in this entry.Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients. {ECO:0000269PubMed:1659668, ECO:0000269PubMed:1659948, ECO:0000269PubMed:20076800, ECO:0000269PubMed:7695243}. Note=The disease is caused by mutations affecting the gene represented in this entry.Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. {ECO:0000269PubMed:15596759, ECO:0000269PubMed:18046642, ECO:0000269PubMed:20522878}. Note=The disease is caused by mutations affecting the gene represented in this entry.Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A- related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise. {ECO:0000269PubMed:10218481, ECO:0000269PubMed:16786525, ECO:0000269PubMed:16832098, ECO:0000269PubMed:17212350, ECO:0000269PubMed:17998485, ECO:0000269PubMed:18203179, ECO:0000269PubMed:18337100, ECO:0000269PubMed:19015483, ECO:0000269PubMed:20076800, ECO:0000269PubMed:8058156, ECO:0000269PubMed:9392583}. Note=The disease is caused by mutations affecting the gene represented in this entry.Myasthenic syndrome, congenital, acetazolamide-responsive (CMSAR) [MIM:614198]: A congenital myasthenic syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation. {ECO:0000269PubMed:12766226}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005216	ion channel activity
GO:0005248	voltage-gated sodium channel activity
GO:0005515	protein binding

Biological Process

GO:0006811	ion transport
GO:0006814	sodium ion transport
GO:0006936	muscle contraction
GO:0019228	neuronal action potential
GO:0034765	regulation of ion transmembrane transport
GO:0035725	sodium ion transmembrane transport
GO:0055085	transmembrane transport
GO:0086010	membrane depolarization during action potential

Cellular Component

GO:0001518	voltage-gated sodium channel complex
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000048 IQ motif, EF-hand binding site
IPR001696 Voltage gated sodium channel, alpha subunit
IPR003915 Polycystic kidney disease type 2 protein
IPR005821 Ion transport domain
IPR008052 Voltage gated sodium channel, alpha-4 subunit, mammalian
IPR010526 Sodium ion transport-associated
IPR013122 Polycystin cation channel, PKD1/PKD2

PFAM

PF00612
PF00520
PF06512
PF08016

PRINTS

PR00170
PR01433
PR01665

PIRSF

SMART

SM00015

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt